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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.

Background Paravalvular regurgitation (PVR) has been known to be the primary determinant of poor left ventricular (LV) mass regression after transcatheter aortic valve replacement (TAVR). However, the incidence of significant PVR has been reduced considerably as TAVR technology evolved rapidly. This study aimed to investigate the time course and impact of LV mass index (LVMi) regression on long-term clinical outcomes in severe aortic stenosis (AS) patients without significant PVR after TAVR. Methods Of 412 patients who underwent TAVR, 146 who had LV hypertrophy (LVMi ≥115 g/m2 for men and ≥ 95 g/m2 for women) at baseline and were alive at one year after TAVR were enrolled. The primary outcome was cardiovascular deaths and the impact of LVMi regression on clinical outcomes were examined. The patients with significant PVR were excluded. Results During a median follow-up of 40 months (interquartile range, 26–58 months), 9 (6.2%) cardiovascular deaths, 21 (14.4%) all-cause deaths, and 9 (6.2%) hospitalizations occurred. In the multivariable analysis, the percentage change of LVMi was an independent predictor of cardiovascular deaths (adjusted hazard ratio [HR], 1.03; 95% confidential interval [CI], 1.01–1.05; P = 0.010), and composite outcome of cardiovascular deaths and rehospitalization for heart failure (adjusted HR, 1.02; 95% CI, 1.00–1.04; P = 0.022). Baseline LVMi, eccentric hypertrophy, and TAVR-induced left bundle branch block were independently associated with LVMi regression. Conclusions In patients with severe AS who received successful TAVR without significant PVR, the degree of LVMi regression is an independent predictor of postoperative outcomes after TAVR.

This study sought to obtain large-scale evidence supporting the clinical usefulness of ergonovine echocardiography.The role of noninvasive ergonovine provocation testing with echocardiographic monitoring of ventricular wall motion (ergonovine echocardiography) needs to be defined.Clinical data of patients who underwent ergonovine echocardiography in 3 tertiary referral hospitals in South Korea were analyzed.Ergonovine echocardiography was performed in 14,012 patients (mean age 52.8 ± 11.1 years; 6,213 [44.3%] women) after exclusion of significant coronary arterial stenosis by functional (treadmill or perfusion scan, n = 9,824) or anatomic test (invasive or computerized tomographic coronary angiography, n = 4,188). Premature termination developed in 0.4% (n = 51), and a positive result was observed in 2,144 patients (15.3%), with variable frequencies according to the diagnosis (acute coronary syndrome [38.2%], variant angina [31.8%], effort angina [14.9%], aborted sudden cardiac death [17.6%], syncope [9.9%]). There was no mortality or development of myocardial infarction during the test. During median follow-up of 11.4 (interquartile range: 7.2 to 15.8) years, death of any cause and cardiovascular death occurred in 494 and 143 patients, respectively. The 10-year overall (96.7 ± 0.2% vs. 91.5 ± 0.6%; p 0.0001) and cardiovascular mortality-free (99.2 ± 0.1% vs. 96.7 ± 0.4%; p 0.0001) survival rates were lower in patients with positive ergonovine echocardiography. Regarding patients with positive test results, the functional test group and the anatomic test group did not show a significant difference in the survival rates. After adjustment of age and male sex, a positive test was an independent risk factor associated with all-cause mortality (hazard ratio: 1.879, 95% confidence interval: 1.548 to 2.280; p 0.001) and cardiovascular death (hazard ratio: 2.903, 95% confidence interval: 2.061 to 4.089; p 0.001).Ergonovine echocardiography for coronary vasospasm diagnosis could be safely performed even without angiographic documentation of fixed coronary stenosis depending on the clinical presentation, and provided important prognostic implication. Ergonovine echocardiography can replace the invasive spasm provocation testing, which has been overlooked unfairly.

BACKGROUND Hypertensive patients are at increased risk of diastolic dysfunction. The hypothesis of this study was that addition of amlodipine would be superior to valsartan in improving diastolic dysfunction associated with hypertension. METHODS In this randomized trial, we randomly assigned 104 controlled, hypertensive patients with diastolic dysfunction to receive either amlodipine 2.5 mg or valsartan 40 mg, in addition to antihypertensive therapy. The primary end point was the change in the ratio of early mitral inflow velocity to early mitral annular relaxation velocity (E/E') from baseline to the 6-month follow-up. Secondary end points included changes in systolic blood pressure (SBP), left ventricular (LV) mass index, and left atrial volume index. RESULTS SBP decreased significantly from baseline in both treatment groups (p < 0.001). E/E' decreased significantly from 13.0 ± 2.2 to 12.0 ± 2.7 in the amlodipine arm and from 14.4 ± 4.3 to 12.7 ± 3.7 in the valsartan arm (p < 0.01 in both groups). The change of E/E' was not significantly different between treatment groups (p = 0.25). There were also no significant between-group differences regarding the changes in SBP, LV mass index, and left atrial volume index. Two patients (3.8%) in the amlodipine group and 1 (16%) in the valsartan group had serious adverse event. CONCLUSIONS In this randomized trial involving controlled hypertensive patients, addition of amlodipine or valsartan was associated with an improvement of diastolic dysfunction, but the effects on diastolic dysfunction did not differ significantly between the treatment groups.

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.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 RVol60 mL.All patients had severe MR based on RVol by the PISA method, but 68 (41.1%) showed RVol by the volumetric method values of60 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).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.

AimsTo evaluate the acute and long-term prognosis of acute aortic syndrome (AAS) according to the disease entity [intramural haematoma (IMH) vs. aortic dissection (AD)] and the anatomical location (type A vs. B).Methods and resultsA total of 1012 patients [672 with AD and 340 with IMH (33.6%)] were enrolled between 1993 and 2015. Compared with AD patients, IMH patients were older and had higher frequency of female sex and distal aorta involvement. The overall crude in-hospital mortality of AAS was 8.6%; type A AD [15.0%; adjusted hazard ratio (aHR) 30.4; 95% confidence interval (CI) 8.62–107.3; P < 0.001], type A IMH (8.0%; aHR 4.85; 95% CI 1.29–18.2; P = 0.019), type B AD (5.0%; aHR 3.51; 95% CI 1.00–12.4; P = 0.051), and type B IMH [1.5%; aHR 1.00 (reference)]. During a median follow-up duration of 8.5 years (interquartile range: 4.0–13.5 years), AD (aHR 2.78; 95% CI 1.87–4.14; P < 0.001) and type A (aHR 2.28; 95% CI 1.45–3.58; P < 0.001) was associated with a higher risk of aortic death. After 90 days, a risk of aortic death was no longer associated with anatomical location (aHR 0.74; 95% CI 0.40–1.36; P = 0.33), but remained associated with disease entity (aHR 1.83; 95% CI 1.10–3.04; P = 0.02).ConclusionThe clinical features, response to treatment strategy, and outcomes of IMH patients were distinct from those of AD patients. Both early and late survival was better for IMH than for AD. In addition to the anatomical location of AAS, the disease entity is an independent factor associated with both acute and long-term mortality in patients with AAS. Further investigation is necessary to confirm the prognostic implication of disease entity in different patient populations.

Objectives This study hypothesized that compensatory mitral leaflet area (MLA) adaptation occurs in patients with persistent atrial fibrillation (AF) without left ventricular (LV) dysfunction but has limitations that augment mitral regurgitation (MR). The study also explored whether asymmetrical annular dilation is matched by relative leaflet enlargement. Background Functional MR occurs in patients with AF and isolated annular dilation, but the relationship of MLA adaptation with annular area (AA) is unknown. Methods Three-dimensional echocardiographic images were acquired from 86 patients with quantified MR: 53 with nonvalvular persistent AF (23 MR+ with moderate or greater MR, 30 MR−) without LV dysfunction or dilation and 33 normal controls. Comprehensive 3-dimensional analysis included total diastolic MLA, adaptation ratios of MLA to annular area and MLA to leaflet closure area, and annular and tenting geometry. Results Total MLA was 22% larger in patients with AF than in controls, thus paralleling the increased AA. However, as AA increased, adaptive indices (MLA/AA ratio and ratio of MLA to closure area) plateaued, becoming lowest in MR+ patients (ratio of MLA to closure area = 1.63 ± 0.17 controls, 1.60 ± 0.11 MR−, 1.32 ± 0.10 MR+; p Conclusions MLA adaptively increases in AF with isolated annular dilation and normal LV function. This compensatory enlargement becomes insufficient with greater annular dilation, and the leaflets fail to match asymmetrical annular remodeling, thereby increasing MR. These findings can potentially help optimize therapeutic options and motivate basic studies of adaptive growth processes.

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 cm 2 ; 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.

A prognostic value of right ventricular (RV) systolic function assessed by echocardiography in patients with acute non-massive pulmonary embolism (PE) remains controversial. The hypothesis was RV free wall strain measured using speckle-tracking echocardiography might be a powerful prognostic factor in those patients. We aimed to evaluate the prognostic value of echocardiographic measurements of RV systolic function for clinical outcomes and to assess the correlation between the echocardiographic RV function parameters in patients with acute non-massive PE. Between November 2013 and September 2016, 144 consecutive patients diagnosed as acute non-massive pulmonary embolism were prospectively enrolled and echocardiographic evaluations were performed within 1 week of diagnosis to measure various parameters of RV systolic function. The primary endpoint was in-hospital events, the composite of in-hospital PE-related death, need of additive treatments such as thrombolysis or pulmonary artery thromboembolectomy, and need of inotropics due to unstable vital sign. Among patients (mean age 60.3 ± 14.7 years, 50% female) with acute non-massive PE, the in-hospital event rate was 11.1% (16 of 144 patients). In multivariate logistic regression analysis, after adjustment of confounding factors such as age, gender, and diabetes mellitus, RV free wall strain [odd ratio (OR) 1.12, 95% confidence interval (CI) 1.04–1.21, p = 0.002] and RV global wall strain (OR 1.20, 95% CI 1.07–1.35, p = 0.002) were independent predictors for in-hospital events. The event rates were significantly different between groups classified based on RV free wall strain with cut-off value of − 15.85% (p

Background Sarcopenia, known as physical frailty, is highly prevalent in older patients and is related to adverse outcomes post-cardiac surgery. However, whether sarcopenia assessment can reclassify an individual patients’ 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 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 one-year mortality rates were 4.7%, 17.6%, and 8.0%, respectively. As the Z-score decreased, early adverse event odds showed a stepwise increase. Sarcopenia were 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 Conclusions Sarcopenic patients had significantly higher risks of early adverse events and long-term mortality after undergoing surgical aortic valve replacement than non-sarcopenic patients. Sarcopenia determined by preoperative computed tomography can enhance the prediction of postoperative outcome risk.

ObjectiveTo 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.MethodsOut 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%).ResultsMaximal 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).ConclusionsDPP-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.

Background Recent reports showing the favorable role of patent foramen ovale (PFO) closure in patients with cryptogenic stroke have raised the issue of selecting optimal candidates. Objectives This study, DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale), evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO, as evaluated by transesophageal echocardiography. Methods Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group. High-risk PFO included PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥2 mm. The primary endpoint was a composite of stroke, vascular death, or Thrombolysis In Myocardial Infarction–defined major bleeding during 2 years of follow-up. Results From September 2011 until October 2017, 120 patients (mean age: 51.8 years) underwent randomization. PFO size, frequency of septal aneurysm (13.3% vs. 8.3%; p = 0.56), and hypermobility (45.0% vs. 46.7%; p > 0.99) were similar between the groups. All PFO closures were successful. The primary endpoint occurred exclusively in the medication-only group (6 of 60 patients; 2-year event rate: 12.9% [log-rank p = 0.013]; 2-year rate of ischemic stroke: 10.5% [p = 0.023]). The events in the medication-only group included ischemic stroke (n = 5), cerebral hemorrhage (n = 1), Thrombolysis In Myocardial Infarction–defined major bleeding (n = 2), and transient ischemic attack (n = 1). Nonfatal procedural complications included development of atrial fibrillation (n = 2), pericardial effusion (n = 1), and pseudoaneurysm (n = 1). Conclusions PFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence. (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588)

Background/Aims: Although the association between intrapulmonary shunt (IPS) and liver cirrhosis is clear, data of repeated contrast echocardiography (CE) before and after liver transplantation (LT) to evaluate factors associated with IPS are limited. Methods: Hand-agitated saline was used for CE and, by assessing left-chamber opacification, IPS was classified as grade 0 to 4. Grade 3/4 constituted significant IPS and hepatopulmonary syndrome (HPS) was defined as significant IPS with the arterial partial pressure of oxygen < 70 mmHg. Results: Before LT, 253 patients underwent CE and the frequency of significant IPS and HPS were 44% (n = 112) and 7% (n = 17), respectively. Child-Pugh score (odds ratio [OR], 1.345; 95% confidence interval [CI], 1.090 to 1.660; p = 0.006) and arterial oxygen content (OR, 0.838; 95% CI, 0.708 to 0.991; p = 0.039) were inde pendent determinants of significant IPS, whereas direct bilirubin (OR, 1.076; 95% CI, 1.012 to 1.144; p = 0.019) was the only variable associated with HPS. Among 153 patients who underwent successful LT, repeated CE was performed in 97 (63%), which showed significant reductions in IPS grade (from 2.6 ± 1.0 to 1.2 ± 1.3, p < 0.001) and the prevalence of significant IPS (from 56% to 20%, p = 0.038). After adjustment for pre-LT IPS grade, time from LT to repeated CE presented negative linear relationship with post-LT IPS grade (r2 = 0.366, p < 0.001) and was the only determinant of post-LT IPS grade (OR, 1.009; 95% CI, 1.003 to 1.014; p = 0.004). Conclusions: Repeated CE is useful to evaluate intrapulmonary vascular change before and after LT. Reversal of IPS after successful LT is time-dependent and fol low-up duration should be considered for accurate assessment of IPS after LT.

A simplified classification of bicuspid aortic valve (BAV) morphology using only the orientation of fused cusps was recently proposed. The aim of this study was to test whether it is useful for showing an association with the type of valvulopathy or aortopathy.BAV phenotype was retrospectively classified in 681 patients (mean age, 59 ± 12 years; 424 men) who underwent aortic valve surgery. Each BAV was classified using both dichotomous (right and left coronary cusp fusion [CCF] vs mixed cusp fusion [MCF]) and conventional methods, and its association with the dominant valvulopathy (aortic stenosis [AS] vs regurgitation) and concomitant aortic surgery was analyzed. Four cardiologists individually reviewed transthoracic echocardiographic images of 100 randomly selected patients to compare the feasibility and accuracy of the two classification methods.The frequencies of BAV CCF and MCF were 53% (n = 361) and 47% (n = 320), respectively. AS was the predominant cause of surgery (n = 546 [80%]), and concomitant aortic surgery was done in 31% (n = 214). Patients with BAV MCF showed a higher frequency of AS (89% vs 73%, P .001) and aortic surgery (38% vs 26%, P .001) than those with BAV CCF. There were independent associations between BAV MCF and AS (odds ratio, 3.32; 95% CI, 1.99-5.54; P .001) as well as aortic surgery (odds ratio, 1.76; 95% CI, 1.26-2.45; P = .001). The feasibility of the classification methods did not differ, but dichotomous classification revealed higher accuracy than conventional (87% [95% CI, 84.1%-90.7%] vs 70% [95% CI, 65.0%-74.3%]) for all four examiners, with higher κ coefficients representing interrater agreement (κ = 0.73 ± 0.06 to 0.83 ± 0.06 [dichotomous method] vs 0.51 ± 0.06 to 0.73 ± 0.06 [conventional method]).The dichotomous classification method is useful for showing the association with the type of valvulopathy or aortopathy, with better diagnostic performance than the conventional method.

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 &lt, 0.05), while valsartan did not (471.2 ± 8.9 µL, p &gt, 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, 0.05). Transforming growth factor-β 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.

Aims To establish geometric predictors of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) patients by use of cardiac computed tomography (CT). Methods and results A total of 141 consecutive patients with HCM who underwent cardiac CT comprised the analytic sample. The degree, pattern, and extent of left ventricular (LV) hypertrophy were evaluated using 3D CT. Abnormality of papillary muscle (PM), mitral valve, and aorto-mitral angle were evaluated quantitatively. Multivariable logistic regression analysis and sensitivity analysis were performed to reliably identify predictors of LVOTO. LVOTO was present among 40 (28.4%) patients. Those with LVOTO displayed a higher prevalence for having a spiral pattern of LV hypertrophy (e.g. 51 vs. 16%, P

Aims Using balloon sizing to determine device size may cause complications and increase procedure time in performing transcatheter closure of atrial septal defect (ASD). We aimed to validate the clinical utility of a formula using measurements from 3D transoesophageal echocardiography (TOE) images in performing the procedure without balloon sizing. Methods and results We enrolled 248 consecutive patients with ASD in a prospective registry. In the first tier (n = 53), we determined the device size before the procedure using our formula and performed balloon sizing during the procedure to verify our decision. In the second tier (n = 195), the procedure was performed without balloon sizing. In the first tier, the estimated device size correlated well with the device size finally implanted (R = 0.961, P

We investigated association between hemodynamic characteristics and aortic dilatation in patients with severe aortic stenosis (AS). Eighty patients with severe AS (mean age, 67.2 ± 12.5 years) who underwent multi-detector computed tomography and phase-contrast magnetic resonance imaging at the ascending aorta were retrospectively analyzed. Patients with an ascending aorta diameter >4 cm had a significantly higher forward flow rate at systole (28.5 ± 6.0 vs. 36.2 ± 8.6 L min, P

The optimal decision regarding whether to repair or replace the tricuspid valve (TV) remains controversial in patients with very severe functional tricuspid regurgitation (TR). We sought to compare clinical outcomes of TV repair versus replacement for very severe TR associated with severe TV tethering. We included 96 consecutive patients (20 men, 58 ± 11 years of age) who had both severe tethering of TV and very severe functional TR and consequently underwent TV surgery during left-sided valve surgery. TV repair was performed on 79 patients (repair group), whereas 17 patients underwent TV replacement (replacement group). The primary end point of the study was defined as the composite of operative mortality, cardiac death, repeat TV surgery, and hospitalization due to congestive heart failure during follow-up. The 2 groups had similar baseline clinical, echocardiographic, and operative characteristics, but operative mortality was significantly higher in the replacement group than in the repair group (p = 0.008). During a median follow-up of 87 months, 19 patients (24%) in the repair group and 8 (47%) in the replacement group attained the composite end point, and TV replacement was independently associated with end points in the Cox proportional hazards analysis after adjustment with propensity score (hazard ratio 4.033, 95% CI 1.470 to 11.071; p = 0.007). In conclusion, compared with TV repair, replacement was associated with higher operative mortality and worse long-term clinical outcomes in patients with very severe functional TR. Repair should be the preferred surgical option even for severe TR associated with more advanced tethering and right ventricular dilatation.

Aims We aimed to compare imaging findings of infective endocarditis between computed tomography (CT) and transoesophageal echocardiography (TEE) using surgical inspection as a reference standard. Methods and results Forty-nine patients (aged 54 ± 17 years, 69% men) who underwent pre-operative CT and TEE for infective endocarditis were included. Twelve of these patients had prosthetic valve endocarditis. Imaging findings of infective endocarditis were classified as vegetation, leaflet perforation, abscess/pseudoaneurysm, and paravalvular leakage. Diagnostic performances of CT and TEE were evaluated using surgical inspection as a reference standard. Interobserver agreements for CT findings were obtained using Cohen's κ test. The detection rates of infective endocarditis per patient with CT and TEE were 93.9% (46/49) and 95.9% (47/49), respectively. In per-imaging analysis, the sensitivities of CT and TEE were not significantly different for both native and prosthetic valve infective endocarditis (sensitivity: vegetation, 100% in TEE and 90.9% in CT; leaflet perforation, 87.5% in TEE and 50.0% in CT; abscess/pseudoaneurysm, 40.0% in TEE and 60.0% in CT; paravalvular leakage, 100% in TEE and 50.0% in CT). Interobserver agreements for CT findings were substantial or excellent (0.79-0.88). Conclusion Cardiac CT can accurately demonstrate infective endocarditis in pre-operative patients with a similar diagnostic accuracy to TEE. The interobserver agreements for the CT findings of infective endocarditis were excellent.

This multicenter, randomized, double-blind, parallel-group phase III clinical trial aimed to investigate the efficacy and safety of a rosuvastatin + amlodipine combination compared with that of rosuvastatin or amlodipine monotherapy in hypertensive patients with dyslipidemia. A total of 106 patients of 15 institutions in Korea were randomly assigned to 1 of 3 treatment groups: rosuvastatin 20 mg + amlodipine 10 mg, amlodipine 10 mg, or rosuvastatin 20 mg. After 8 weeks of treatment, the mean ± SD of change in mean sitting systolic blood pressure (msSBP) was -22.82 ± 12.99 mm Hg in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. The percentage of patients whose msSBP decreased ≥20 mm Hg or msDBP decreased ≥10 mm Hg was also highest in this group (74.29%). The mean ± SD percentage change in low-density lipoprotein cholesterol (LDL-C) level from baseline after 8 weeks was -52.53% ± 11.21% in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. More patients in the rosuvastatin + amlodipine group achieved their target LDL-C goal at 8 weeks, compared with the other treatment groups (97.14%). No serious adverse events or adverse drug reactions were observed in all groups. In hypertensive patients with dyslipidemia, combination treatment with rosuvastatin 20 mg + amlodipine 10 mg effectively reduced blood pressure and LDL-C levels while maintaining safety.

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.

Background Left ventricle (LV) in patients with aortic stenosis (AS) faces a double hemodynamic load incorporating both valvular stenosis and reduced systemic arterial compliance (SAC). This study aimed to evaluate the impact of global LV afterload on LV hypertrophy (LVH) before and after aortic valve replacement (AVR). Methods The study cohort included 453 patients (247 males; mean age, 64 ± 11 years) who underwent AVR. Pre- and post-AVR echocardiographic examinations were retrospectively analyzed including an index of valvuloarterial impedance (ZVA) and LV mass index/LV end-diastolic volume index (LVMI/LVEDVI) as a parameter of LVH. Results Pre-AVR LVMI/LVEDVI was 2.7 ± 0.9 g/mL with an aortic valve area (AVA) of 0.6 ± 0.2 cm2. ZVA was 5.9 ± 1.9 mm Hg/mL/m2 and showed a stronger correlation (β = 0.601, p < 0.001) with pre-AVR LVMI/LVEDVI than indexed AVA (β = 0.061, p = 0.19), transvalvular peak velocity (β = 0.211, p < 0.001). During a median follow-up of 3.5 years, patients had a 18.8 ± 10.4% decrease in the LV geometry index with a decrease in SAC from 1.20 ± 0.48 to 1.00 ± 0.38 mL/m2/mm Hg (p < 0.001). Pre-AVR LV ejection fraction (r = 0.284, p < 0.001) and ZVA (r = 0.523, p < 0.001) were independent factors associated with LVH regression in 322 patients with follow-up duration >1 year after AVR. Conclusion ZVA is a major determinant of concentric remodeling in AS before AVR and LVH regression after AVR, which should be incorporated in routine evaluation of AS.

Objectives The timing of aortic valve replacement (AVR) remains controversial in symptomatic patients with normal flow, low-gradient severe aortic stenosis (AS) and preserved LVEF. We sought to compare long-term mortality of early AVR versus a watchful observation strategy. Methods From 2000 to 2011, we prospectively evaluated 284 consecutive symptomatic patients (136 men, age 68±10 years) with normal flow, low-gradient severe AS and preserved LVEF who were potential candidates for early AVR. Normal flow, low-gradient severe AS was defined as indexed aortic valve area 2 /m 2 with mean gradient 2 . Early AVR was performed on 98 patients (early AVR group), while the watchful observation strategy was selected for 186 patients (watchful observation group). Patients in the watchful observation group were referred for AVR if mean gradient was ≥40 mm Hg during follow-up. Results There were no significant differences between the early AVR and the watchful observation groups for the risk of overall mortality (HR 0.94 for the early AVR; 95% CI 0.51 to 1.73) or for the estimated actuarial 8-year mortality rates (17±5% vs 27±5%, p=0.84) in the overall cohort. Society of Thoracic Surgeons score, comorbidity index, age, coronary artery disease, aetiology of AS and performance of AVR were associated with overall survival. For 83 propensity-score-matched pairs, the risk of overall death was not significantly different between the two groups (HR 1.13 for the early AVR, 95% CI 0.55 to 2.35, p=0.74). Conclusions Early AVR and watchful observation strategy show similar survival in symptomatic patients with normal flow, low-gradient severe AS and preserved LVEF. Watchful observation with timely performance of AVR should be considered a therapeutic option.

BACKGROUND AND OBJECTIVES Clinical data for Korean patients with bicuspid aortic valve (BAV) that underwent aortic valve (AV) surgery are currently limited. METHODS Data for 1,160 consecutive adult BAV patients who underwent AV surgery from 2000 to 2014 in 4 tertiary referral centers were retrospectively analyzed. A standard case report form was used for clinical and echocardiographic parameters. RESULTS Mean age at the time of AV surgery was 59±13 years. The most common cause of AV surgery was aortic stenosis (AS, 892 [77%]), followed by aortic regurgitation (AR, 199 [17%]), and infective endocarditis (69 [6%]). AS showed a skewed peak in the aged population and was the predominant cause of AV surgery (87%) in patients ≥50 years of age, whereas AR (46%) and active infective endocarditis (19%) were more common in younger patients (p

Background Late prognosis after successful percutaneous mitral commissurotomy (PMC) is unclear. We compared late results of PMC using Inoue versus double-balloon techniques up to 25years in a randomized trial. Methods Between 1989 and 1995, 302 patients (77 men, 41±11years) with severe mitral stenosis were randomly assigned to undergo PMC using Inoue (n=152; group I) or double-balloon technique (n=150; group D). The end points were the composite events of death, mitral surgery, repeat PMC, or deterioration of New York Heart Association (NYHA) class ≥3. Results During median follow-up of 20.7years (maximum, 25.6), clinical events occurred in 82 (53.9%) patients in group I (37 deaths, 44 mitral surgeries, 9 repeat PMCs, 3 NYHA class ≥3) and in 79 (52.7%) patients in group D (34 deaths, 51 mitral surgeries, 5 repeat PMCs, 4 NYHA class ≥3). Event-free survival rates at 24years were not significantly different between group I and group D (40.8% and 42.6%, respectively; hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.65–1.20; P =.423). On multivariate analysis, absence of post-PMC commissural mitral regurgitation (MR) (HR, 1.84; 95% CI, 1.28–2.63; P =.001) and immediate post-PMC mitral valve area (MVA) 2 (HR, 1.53; 95% CI, 1.04–2.25; P =.031) were independently correlated with clinical events after successful PMC. Conclusions The Inoue and double-balloon methods showed similar good clinical outcomes up to 25years, and the achievement of effective commissurotomy to develop post-PMC commissural MR or immediate post-PMC MVA ≥1.8cm 2 is important in optimizing the late results of PMC.

Background Both stress cardiomyopathy (SCMP) and acute myocardial infarction (AMI) present with similar clinical symptoms and signs, and apical akinesis. Hypothesis: Quantitative segmental analysis of myocardial contrast echocardiography (MCE) helps to differentiate AMI from SCMP. Methods Real-time MCE was performed in 33 consecutive patients who presented with an acute symptom/sign and a new apical akinesis on echocardiography. In 18 left ventricular (LV) myocardial segments, a replenishment curve was obtained in each segment to measure peak plateau myocardial contrast intensity (MCI) (A) and the replenishment curve slope (β). The calibrated MCI was also measured in each segment. Results Among 33 patients, 22 were diagnosed with SCMP and 11 were diagnosed with AMI according to comprehensive diagnostic criteria. A, β, Aβ, and the calibrated MCI were lower in akinetic than in normokinetic segments in both the SCMP and AMI groups. In the akinetic segments, A, β, Aβ, and the calibrated MCI in SCMP patients were each higher than those in AMI patients. In patient-based analyses, areas under the ROC curves of A, β, Aβ, and the calibrated MCI for diagnosing AMI were 0.769, 0.607, 0.822, and 0.934, respectively. The optimal cutoff values to diagnose AMI were Aβ

This phase 3, multiregional, randomized, double-blind, placebo-controlled study assessed the efficacy/safety profile of anacetrapib added to ongoing therapy with statin ± other lipid-modifying therapies in patients with hypercholesterolemia who were not at their low-density lipoprotein (LDL-C) goal (as per the National Cholesterol Education Program Adult Treatment Panel III guidelines) and in those with low high-density lipoprotein cholesterol (HDL-C). Patients on a stable dose of statin ± other lipid-modifying therapies and with LDL-C ≥70 to

Although statins reduce cardiac events in hypertensive patients with cardiovascular risk factors, the effect of statins on coronary flow reserve (CFR) has not been examined. We tried to examine the effect of rosuvastatin on CFR in hypertensive patients at cardiovascular risk. CFR was studied in 56 hypertensive patients (40 men, 61 ± 9 years) with cardiovascular risk factors and without coronary artery disease in a prospective clinical trial. Using Doppler echocardiography, coronary flow velocity in the distal left anterior descending artery was recorded at baseline and during intravenous adenosine infusion, and CFR was defined as the ratio of hyperemic to basal average peak diastolic flow velocity. The primary efficacy measure was defined as the change in CFR after rosuvastatin therapy for 12 months. CFR was measured successfully in 55 of 56 enrolled patients (98%). CFR was 3.16 ± 0.44 at baseline and negatively correlated with age (R = -0.30, p = 0.025). All patients continued rosuvastatin 10 mg/day without any serious adverse events. After rosuvastatin therapy, serum total cholesterol, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein significantly decreased from 222 ± 18 to 142 ± 20 mg/dl, 148 ± 21 to 85 ± 18 mg/dl, and 1.7 ± 2.9 to 1.2 ± 3.1 mg/L, respectively (all p0.01). CFR significantly increased from 3.16 ± 0.44 to 3.31 ± 0.42 (p0.001). The change in CFR correlated with the change in low-density lipoprotein cholesterol (R = -0.28, p = 0.040) but not with the change in high-sensitivity C-reactive protein. In conclusion, CFR was significantly improved after 12 months of rosuvastatin therapy in hypertensive patients at cardiovascular risk and average levels of serum cholesterol.

Objectives This study sought to compare long-term outcomes of early surgery with a conventional treatment strategy in asymptomatic patients with severe mitral regurgitation (MR). Background The timing of surgery in asymptomatic severe MR remains controversial. Methods From 1996 to 2009, 610 consecutive asymptomatic patients (364 men, 50 ± 14 years of age) with severe degenerative MR and preserved left ventricular function were evaluated prospectively. Early surgery was performed on 235 patients, and the conventional treatment strategy was chosen for 375 patients. We compared overall mortality, cardiac mortality, and cardiac events (operative mortality, cardiac mortality, repeat surgery, and urgent admission due to heart failure) between the 2 treatment strategies in the propensity score–matched cohort. Results For the 207 propensity score–matched pairs, early surgery had a lower risk of cardiac mortality (hazard ratio [HR]: 0.109; 95% confidence interval [CI]: 0.014 to 0.836; p = 0.033) and cardiac events (HR: 0.216; 95% CI: 0.083 to 0.558; p = 0.002) than conventional treatment. On Cox proportional hazard model analysis, the risk of cardiac events was significantly lower in the early surgery group than in the conventional treatment group in patients aged 50 years of age and older (HR: 0.221; 95% CI: 0.086 to 0.567; p = 0.002), but not significantly different in those younger than 50 years of age (p = 0.20). Conclusions Compared with conservative management, early surgery is associated with significant long-term reductions of cardiac mortality and cardiac events in asymptomatic severe MR. These benefits were evident among patients age 50 years of age and older.

We present a case of 48-year-old male who presented with coronary artery fistula draining into left ventricle. Transthoracic echocardiography showed abnormal blood flow draining into left ventricle, with enlarged coronary arteries and multiple vascular structures around ventricular myocardium. Coronary computed tomography revealed dilatation of entire left coronary artery which was wrapping around left ventricle, and draining into the posterior side of left ventricle. He did not undergo any invasive treatment, because he was not symptomatic.

We aimed to determine whether global longitudinal strain (GLS) had a prognostic value in patients with severe aortic stenosis (AS) and preserved EF undergoing transcatheter aortic valve replacement (TAVR) Among 412 consecutive patients who underwent TAVR, 346 patients (mean age: 78± 5) with

We sought to investigate the impact of left ventricular mass (LVM) regression on clinical outcome and predictors of LVM regression in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) Of 412 patients who underwent TAVR between 2010 and 2018, 146 patients

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.

The present study aimed to investigate geometric remodeling of the mitral valve (MV) and to identify the geometric determinants of mitral regurgitation (MR) severity in patients with significant MR secondary to a rheumatic or prolapse etiology. We studied 90 consecutive patients in normal sinus rhythm, including 70 patients showing significant MR (52 with prolapsed/flail and 18 with rheumatic MV) and 20 controls with normal MV without MR. A full volume image was acquired using transesophageal echocardiography, and geometric analysis of the MV leaflet was performed with dedicated software. Areas of the MV annulus and the anterior and posterior leaflets were larger in the rheumatic and prolapsed MV than in the normal controls. No difference was found between the rheumatic and prolapsed MR in those parameters, except that the posterior leaflet area was smaller in rheumatic MR than in prolapsed MR. The leaflet to annulus area ratio was lower and the anterior to posterior leaflet area ratio was higher in the rheumatic MR group than in the prolapsed MR group. A large anteroposterior annulus diameter and small posterior leaflet tenting angle were independently associated with the effective regurgitant orifice area in rheumatic MV, although the leaflet to annulus area ratio was independently associated with the effective regurgitant orifice area in the prolapsed MV. In conclusion, similarities and differences in geometric MV remodeling exist between rheumatic and prolapsed MR. The knowledge of those quantitative differences could open the way to precise planning of surgery tailored to the underlying pathologic entity.

Objectives We sought to define the clinical importance of an integrated classification of bicuspid aortic valve (BAV) phenotypes and aortopathy using multidetector computed tomography (MDCT). Background An association between BAV phenotypes and the pattern of valvular dysfunction or bicuspid aortopathy has yet to be definitely established. Methods The study cohort included 167 subjects (116 men, age 54.6 ± 14.4 years) who underwent both MDCT and transthoracic echocardiography from 2003 to 2010. Two BAV phenotypes—fusion of the right and left coronary cusps (BAV-AP) and fusion of the right or left coronary cusp and noncoronary cusp (BAV-RL)—were identified. Forty-five patients showed normal aortic dimensions and were classified as type 0. In the remaining patients, hierarchic cluster analysis showed 3 different types of bicuspid aortopathy according to the pattern of aortic dilation: type 1 (aortic enlargement confined to the sinus of Valsalva [n = 34]), type 2 (aortic enlargement involving the tubular portion of the ascending aorta [n = 49]), and type 3 (aortic enlargement extending to the transverse aortic arch [n = 39]). Results The prevalence of BAV-AP and BAV-RL was 55.7% and 44.3%, respectively. Comparing BAV-AP and BAV-RL, no differences in age or in the prevalence of male sex were determined. However, significant differences in the valvular dysfunction pattern were noted, with moderate-to-severe aortic stenosis predominating in patients with BAV-RL (66.2% vs. 46.2% in BAV-AP; p = 0.01), and moderate-to-severe aortic regurgitation in BAV-AP (32.3% vs. 6.8% in BAV-RL; p Conclusions The patterns of valvular dysfunction and bicuspid aortopathy differed significantly between the 2 BAV phenotypes, suggesting the possibility of etiologically different entities.

Background Various left ventricular (LV) vortex parameters obtained during contrast echocardiography (CE) have been recently described. The aim of this study was to investigate their determinants and associations with conventional hemodynamic variables. Methods CE was performed and LV pressure was simultaneously measured during pharmacologic inotropic modulation in 8 mongrel dogs. Customized software was used to assess both vortex geometric parameters (vortex depth [VD], length [VL], width [VW], transverse position, and sphericity index [SI]) and pulsatility parameters (relative strength [RS], vortex relative strength [VRS], and vortex pulsation correlation [VPC]). The associations between each of these parameters and conventional indices representing LV systolic and diastolic function were analyzed. Results VD and VW did not change significantly during pharmacologic modulation, whereas VL (P = 0.0034) and SI (P = 0.001) showed significant and progressive linear decreases from baseline during dobutamine infusion. Significant linear changes during positive and negative inotropic modulation were observed in all pulsatiliy parameters (P

To evaluate factors associated with aortic enlargement in patients with a bicuspid aortic valve (BAV) and the impact of isolated aortic valve replacement (AVR).A retrospective analysis of clinical data in a tertiary referral hospital.We performed a cross-sectional analysis of 595 patients with BAV to assess variables determining maximal ascending aortic dimension. To measure annual dilatation rates, baseline and follow-up echocardiograms were analysed in 70 patients with BAV (BAV-AVR group) and 48 with a tricuspid aortic valve (TVA-AVR group) who underwent isolated AVR, and compared with 65 patients with BAV who did not undergo AVR (BAV-NAVR group).Aortic regurgitation (AR) severity was associated with aortic sinus diameter (p0.001), whereas aortic stenosis severity with the tubular diameter (p0.001). Multivariate analysis showed that age was an independent factor for both sinus and tubular diameter with AR severity being for aortic sinus diameter and moderate to severe aortic stenosis or AR being for aortic tubular diameter. Despite younger age and lower prevalence of moderate to severe valvular dysfunction at baseline, the annual dilatation rates at sinus and tubular part were significantly higher in the BAV-NAVR than in the BAV-AVR and TAV-AVR groups (p0.05 each), which did not differ in the BAV-AVR and TAV-AVR groups (p=0.402 for sinus and p=0.394 for tubular part).Age-dependent aortic enlargement associated with significant valvular dysfunction and the protective effects of isolated AVR in patients with BAV indicate that valvular dysfunction is a major determinant to the development of aortopathy.

To compare mitral valve area (MVA) measurements obtained by 2D transthoracic planimetry and 3D transoesophageal echocardiography (TOE) in patients with mitral stenosis (MS), and to determine the causes of discrepancies between the two techniques.Reliability and agreement study.Tertiary referral centre.Eighty-seven patients with MS.MVA was determined by transthoracic 2D planimetry and 3D TOE. Clinical and echocardiographic variables were evaluated. The angle (Mα) between the lines of the true mitral valve (MV) tip and the echo beam-to-MV tip was measured at early diastole from the parasternal long-axis view obtained from 2D echocardiography.Although MVA measurements using 2D planimetry and 3D TOE showed good agreement (intraclass correlation coefficient, 0.853; p0.001), 2D planimetry overestimated MVA by 0.19±0.2 cm(2) compared with 3D TOE (p0.001). Left atrial (LA) dimension obtained from the parasternal long-axis view at end-systole (p=0.012), Mα (p0.001), and left ventricular ejection fraction (p=0.022) were independent determinants of the MVA difference (MVA by 2D-MVA by 3D TOE; MVA(2D-3D)) according to multiple linear regression analysis. The LA dimensions correlated with Mα (r=0.352, p=0.001). The best cut-off values for predicting significant overestimation by 2D planimetry (MVA(2D-3D)0.2 cm(2)) were LA dimension ≥49 mm (78% sensitivity, 72% specificity) and Mα≥9.5° (56% sensitivity, 89% specificity).Because 2D planimetry tends to overestimate MVA, 3D TOE should be considered for accurate MVA assessment, especially in patients with a large LA and large Mα.

Aims Understanding normal asymmetry in the aortic root could aid in the development of new surgical repair techniques or devices with improved haemodynamic performance. The purpose of this study was to assess geometric asymmetry and age-related changes in the normal aortic root using 3D computed tomography. Methods and results The institutional review board approved this retrospective study of 130 normal subjects (mean age, 51.4 years; 58 men). Specialized 3D software measured individual cusp sinus volumes (CSVs), cusp surface areas (CSAs), and intercommissural distances (ICDs). Age-related aortic root changes were evaluated with simple correlation, ANOVA test among age groups, and multivariable linear regression analyses. The CSV and CSA of left coronary cusp (LCC) were significantly smaller than those of right coronary cusp (RCC) and non-coronary cusp (NCC) (both, P < 0.001) in all age groups. The mean ratios of RCC or NCC-to-LCC were 1.38 and 1.36 for CSV, 1.19 and 1.20 for CSA, and 1.21 and 1.06 for ICD, respectively. The CSV and ICD increased in older age with weak-to-moderate correlation coefficients in both men and women. By multivariable linear regression, CSVs and ICDs of all cusps showed a positive correlation with age ( P < 0.05), and the female gender was associated with a smaller size of the CSV and CSA. Conclusions The LCC was significantly smaller than the other two cusps, and the aortic root size increased with age.

Background The effect of the atrial septal defect (ASD) shape on ASD size measurements remains unclear. We assessed the relationships between the stretched balloon diameter (SBD) and the diameters measured using two-dimensional and three-dimensional (3D) transesophageal echocardiography (TEE) and evaluated the effect of ASD shape on these relationships in patients with secundum ASD. Methods We prospectively enrolled 107 consecutive patients who underwent transcatheter closure of ASD. The SBDs and ASD diameters on two-dimensional and 3D-TEE were measured. The circular index of the ASD was defined as the ratio of the maximal diameter to the minimal diameter on the 3D-TEE image. All patients were clinically followed up for a median of 1.3 months after the procedure. Results The correlations and agreements between measurements were significantly better in patients with a round (circular index less than 1.5) than with an oval ASD. The differences between the SBDs and maximal diameter on 3D-TEE images were significantly smaller in patients with a large oval ASD than in the other patients. The differences between the size of the devices finally implanted and maximal diameter on 3D-TEE images were smaller in patients with a large oval than with a round ASD. On multivariate linear regression analysis, a formula of the relationship between the finally selected device size and 3D-TEE parameters was constructed: device size = 0.964 × maximal diameter on 3D-TEE image − 2.622 × circular index + 7.084. No major complications, including device embolization, developed during follow-up. Conclusions The relationships between the SBDs and maximal diameters measured on two-dimensional and 3D-TEE images are influenced by the ASD shape and size. Therefore, the ASD shape, as well as the size, should be considered when the device size is determined without SBD measurement.

Objectives Specific guidelines for initial dosing of warfarin in ischaemic stroke patients have not been developed. Therefore, we have developed an age- and weight-adjusted warfarin initiation nomogram (AW-WIN) for ischaemic stroke patients and then evaluated the efficacy and safety of AW-WIN compared with physician-determined warfarin dosing (PDWD). Methods The age- and weight-adjusted warfarin initiation nomogram was administered to 104 acute ischaemic stroke patients between January 2008 and February 2009. A historical control group (PDWD) of 96 patients was selected from comparable patients who were discharged with warfarin during the previous year. Time-to-therapeutic international normalized ratios (INRs) and the incidence of excessive anticoagulation were compared in the AW-WIN and PDWD groups. Results The general characteristics, risk factors, and stroke mechanism of the AW-WIN and PDWD groups did not differ significantly. The mean time to INR ≥ 2.0 was significantly shorter in the AW-WIN than in the PDWD group (4.9 ± 0.7 vs. 6.2 ± 0.8 days, P = 0.0008). After adjustment for potential confounding variables, the AW-WIN group reached target INR faster than the PDWD group (hazard ratio, 1.76; 95% confidence interval, 1.26–2.45; P = 0.001). The time-to-therapeutic INR ≥1.7 was shorter (P = 0.0002), the proportion of patients with therapeutic INR (2–3) at 5 days was higher (P = 0.002), and the rate of excessive anticoagulation of ≥3.5 INR during hospitalization was lower (P = 0.024) in the AW-WIN than in the PDWD group. Conclusions AW-WIN reduces the time to target INR and the risk of excessive anticoagulation. AW-WIN may be an efficient and safe method of anticoagulation during the acute phase of ischaemic stroke.

Surgical indications in patients with severe chronic aortic regurgitation (AR) and normal left ventricular (LV) ejection fractions (EF) remain to be established. The aim of this study was to identify prognostic indicators after surgery in patients with severe AR and normal LV systolic function. Preoperative clinical and echocardiographic characteristics were evaluated in 284 consecutive patients with chronic severe AR who underwent aortic valve surgery. Of these patients, 169 had normal (≥50%) and 115 had depressed (50%) preoperative LV EFs. All-cause mortality was observed for a median of 39.9 months. Of 284 patients, 7 (4.4%) with normal LV EFs and 15 (12.0%) with depressed LV EFs died during follow-up after aortic valve surgery (p = 0.017). In patients with normal EFs, multivariate Cox regression analysis showed that large LV end-systolic dimension and low plasma hemoglobin level were independent predictors of postsurgical mortality. Receiver-operating characteristic analysis showed that LV end-systolic dimension ≥45 mm and hemoglobin level13.4 g/dl were the best cut-off values for postoperative mortality. In conclusion, preoperative LV end-systolic dimension and hemoglobin level are independent prognostic factors of survival after aortic valve surgery in patients with chronic severe AR and normal LV EFs.

The aim of the present study was to evaluate the mechanism of diastolic dysfunction (DD) after aortic valve replacement (AVR) in patients with aortic stenosis (AS).Supine bicycle exercise Doppler echocardiography (EDE) with measurement of early diastolic peak velocities of transmitral flow (E) and mitral septal annular movement (E') was performed in 38 patients with AS at least 24 months after AVR and in 19 sex- and age-matched normal controls. AS patients had a 27.4±32.7% decrease in the ratio of left ventricular (LV) mass index to LV end-diastolic volume index (LVMI/LVEDVI) after AVR. Pre-AVR E' was significantly lower in AS patients (4.3±1.6 cm/s vs. 7.7±1.6 cm/s, P0.005), resulting in a higher E/E' (16.7±5.4 vs. 9.3±1.8, P0.001). E/E' at rest did not change significantly after AVR. Both E and E' increased progressively with exercise, and the increase in E' (P0.001) but not E (P=0.675) was greater in normal controls than in AS patients (P0.001). Peak E/E'13 during EDE was more common in AS patients than in controls (89.5%, 34/39 vs. 0%, 0/19, P0.001). On multivariate analysis, LVMI/LVEDVI (Y=8.703+4.199X, r=0.433, P=0.001) was the only factor associated with peak E/E' during EDE.Persistent DD is present after AVR, due primarily to failure in normal physiologic augmentation of LV relaxation during exercise, associated with incomplete or inadequate regression of LV hypertrophy.

Background Paravalvular leakage after open heart surgery is notoriously common in patients with aortic regurgitation (AR) due to Behcet's disease. The aim of this study was to test whether initial echocardiographic findings are useful to predict recurrent AR. Methods Lesion severity on preoperative echocardiography was scored for redundant aortic valve cusp (0–2 points), aortic pseudoaneurysm (0–2 points), and dissection of the adjacent interventricular septum (0–2 points) in 22 patients with severe AR due to Behcet's disease (13 men; mean age, 42.4 ± 11.5 years), which was confirmed by histologic examination after open heart surgery. Results Recurrent AR developed in 13 patients at a median of 12.6 months (range, 2.4–70.3 months) after the first operation, and 10, four, and one patient underwent second, third, and fourth surgery, respectively, to control recurrent AR; three patients died. Those patients with recurrent AR had a significantly higher incidence of repeat surgery or death (84.6% [11 of 13] vs 0%, P = .015). Multivariate analysis showed that perioperative immunotherapy (hazard ratio, 0.002; 95% confidence interval, 0.001–0.1761; P = .006) and total echocardiographic score (hazard ratio, 2.843; 95% confidence interval, 1.350–5.991; P = .006) were independent factors associated with recurrent AR. The 1-year, 3-year, and 5-year AR-free survival rates were 73 ± 10%, 46 ± 12%, and 39 ± 12%. The optimal cutoff value for total echocardiographic score was 3.0, and the 5-year AR-free survival rates were significantly lower in patients with scores ≥ 3 (20 ± 13% vs 50 ± 19%, P = .022). Conclusions This retrospective study confirms that initial echocardiographic features can provide useful prognostic information in patients with AR due to Behcet's disease.

We aimed to compare conventional echocardiographic versus speckle tracking-derived parameters in predicting postoperative left ventricular (LV) dysfunction and clinical outcomes after successful mitral valve repair in patients with mitral regurgitation.In 147 consecutive patients in sinus rhythm with severe MR, two-dimensional echocardiography and speckle-tracking imaging for global longitudinal, circumferential, and radial strains and strain rates were performed within 30 days before successful mitral valve repair. Echocardiography was repeated within 7 days in all patients, and more than 3 months after surgery in 112 patients. Clinical events were evaluated for 21±17 months.Multivariate linear regression analysis showed that preoperative LV systolic dimension (p=0.004) and volume (p=0.001) were independent determinants of immediate postoperative LV ejection fraction. Preoperative LV end-systolic dimension (p=0.004), LV ejection fraction (p=0.017), and circumferential strain (p=0.029) were independent predictors of late follow-up LV ejection fraction. By Cox regression analysis, preoperative end-systolic LV dimension (hazard ratio 1.26 for every 1 mm, 95% confidence interval 1.11 to 1.44, p0.001) was the only predictor of hospital admission for heart failure. The best cutoff values of LV end-systolic dimension (≥41 mm) and volume (≥85 mL) for predicting postoperative severe LV dysfunction (ejection fraction0.35) identified patients at high risk for event-free survival, but those of speckle-tracking parameters did not.Preoperative LV remodeling parameters, such as LV end-systolic dimension and volume, are superior to speckle tracking-derived deformation parameters in predicting LV dysfunction and clinical events after successful mitral valve repair in patients with severe mitral regurgitation.

Background Noninvasive calculation of pulmonary vascular resistance (PVR) has been reported to be feasible. We therefore evaluated whether baseline PVR could predict clinical outcomes in patients with acute pulmonary thromboembolism (aPTE). Methods The study cohort consisted of 54 patients with aPTE who underwent both pretreatment and follow-up echocardiography. Doppler-derived PVR was calculated using the following equation: PVR (Woods unit [WU]) = (peak tricuspid regurgitant velocity [TRV max ]/time-velocity integral of right ventricular outflow tract) × 10 + 0.16. Adverse clinical events included all-cause death and persistent pulmonary hypertension (TRV max >3.5 m/sec) on follow-up echocardiography. Results During a clinical follow-up time of 2.4 ± 1.7 years, 16 patients experienced adverse events (death [ n = 14]; persistent pulmonary hypertension [ n = 8]). Patients who developed adverse events were significantly older than those who did not (68.0 ± 13.8 years vs 56.9 ± 15.4 years, P = .02) and showed higher initial PVR (4.5 ± 1.4 WU vs 3.5 ± 1.0 WU, P = .01) and TRV max (3.9 ± 0.6 m/sec vs 3.6 ± 0.5 m/sec, P = .02). The best cutoff value of PVR for predicting adverse events was 4.5 WU (area under the curve = 0.71, P = .02), with a sensitivity and specificity of 63% and 90%, respectively. PVR >4.5 WU (hazard ratio 5.68; 95% CI, 1.89–16.95; P = .002) and older age (hazard ratio per 10 years = 1.47; 95% CI, 1.02–2.12; P = .04) were independent factors associated with the development of adverse events. The 6-year overall survival (16% ± 14% vs 87% ± 6%, P .0001) and event-free survival (15% ± 13% vs 84% ± 6%, P .0001) rates differed according to initial PVR. Conclusion Echocardiographic estimation of PVR provides important prognostic information in patients with aPTE.

BACKGROUND AND OBJECTIVES Right ventricle (RV) remodeling can determine tricuspid valve (TV) geometry and the severity of functional tricuspid regurgitation (TR). SUBJECTS AND METHODS In 53 patients with various degrees of functional TR and in sinus rhythm, RV and TV geometries were analyzed using real-time 3-dimensional echocardiography, including tenting angles of 3 leaflets, septal-lateral and antero-posterior tricuspid annulus diameters and inlet RV dimensions, mid-RV septal-lateral dimension, and the distance between annulus and apex. A mid-systole frame when the TV tenting is smallest was selected for the analysis. RV end-diastolic and end-systolic volumes were measured. The severity of functional TR was determined by distal jet area. RESULTS TR distal jet area was mainly determined by septal-lateral annulus diameter (p

Background Because stress-induced cardiomyopathy (SIC) is increasingly being observed during routine daily practice, we sought to explore the clinical features and factors that determine the outcome of SIC in a tertiary referral hospital. Methods Patients with typical left ventricular (LV) takotsubo (apical ballooning) or inverted takotsubo on 2-dimensional echocardiography were prospectively enrolled, and their clinical data were analyzed. Results Over a 63-month period, 56 consecutive patients (median age and interquartile range=64 years [52-74 years]) were identified. Women comprised 79% (44/56) of all patients. The triggering events were acute medical illness, including sepsis and hypoxemia in 29 patients (52%, group A), in-hospital surgery/procedure in 17 patients (30%, group B), and emotional stress in 10 patients (18%, group C). Chest pain was more frequently observed in group C (50%) than in groups A (14%) and B (6%) ( P = .021), whereas dyspnea was the presenting symptom in groups A and B. Typical takotsubo and inverted takotsubo were observed in 48 and 8 patients, with a median ejection fraction of 33%. Other abnormalities included dynamic LV outflow tract obstruction (n = 2), LV thrombus (n = 2), and right ventricular dysfunction (n = 12). Nine deaths (16%) occurred during hospitalization. The groups did not differ in mortality. The Acute Physiology and Chronic Health Evaluation II score (odds ratio 1.405; 95% confidence interval, 1.091-1.810; P = .009) and absence of LV function recovery within 1 week (ejection fraction P = .036) were independent factors associated with mortality. During clinical follow-up up to 6 months, 3 more patients died, 2 of whom had recurrences of SIC. Conclusions SIC in a tertiary referral hospital was mainly associated with physical stressors and characterized by diverse clinical presentations, high mortality, and occasional fatal recurrences.

The association between the anatomic characteristics obtained by omni-plane transesophageal echocardiography (TEE) and stroke recurrence in patients with cryptogenic stroke and patent foramen ovale (PFO) remains unclear. In the present longitudinal follow-up study, we sought to investigate whether PFO findings assessed by TEE can predict stroke recurrence. Of the 1,014 consecutive patients with acute ischemic stroke referred for TEE, 184 (mean +/- SD age, 51 +/- 14 years) were classified as having cryptogenic stroke with PFO, and follow-up data were available for 181 patients. During follow-up (median 3.5 years), 14 patients (7.7%) experienced stroke recurrence. Multivariate analysis showed that atrial septal aneurysm or hypermobility of the atrial septum (hazard ratio 6.04, 95% confidence interval 1.84 to 19.86, p = 0.003) and PFO size (hazard ratio 3.00, 95% confidence interval 1.96 to 4.60, p