Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was 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, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

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.).

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.

Clinical impact of mild to moderate pulmonary hypertension in living-donor liver transplantation.

Severe pulmonary hypertension (PHT) is a contraindication to liver transplantation (LT); however, the prognostic implication of mild to moderate PHT in living-donor LT (LDLT) is unknown. The study cohort retrospectively included 1307 patients with liver cirrhosis who underwent LDLT. PHT was defined as a mean pulmonary artery pressure (PAP) of ≥25 mmHg, measured intraoperatively just before surgery. The primary endpoint was graft failure within 1 year after LDLT, including retransplantation or death from any cause. The secondary endpoints were in-hospital adverse events. In the overall cohort, the median Model for End-stage Liver Disease-Sodium (MELD-Na) score was 19, and 100 patients (7.7%) showed PHT. During 1-year follow-up, graft failure occurred in 94 patients (7.2%). Patients with PHT had lower 1-year graft survival (86% vs. 93.4%, P = 0.005) and survival rates (87% vs. 93.6%, P = 0.011). Mean PAP was associated with a high risk of in-hospital adverse events and 1-year graft failure. Adding the mean PAP to the clinical risk model improved the risk prediction. In conclusion, mild to moderate PHT was associated with higher risks of 1-year graft failure and in-hospital events, including mortality after LDLT in patients with liver cirrhosis. Intraoperative mean PAP can help predict the early clinical outcomes after LDLT.

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.

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.

Differential clinical features and long-term prognosis of acute aortic syndrome according to disease entity.

AIMS: To 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 RESULTS: A 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). CONCLUSION: The 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.

Prognostic value of echocardiographic parameters for right ventricular function in patients with acute non-massive pulmonary embolism.

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 < 0.001). RV strain assessed with speckle-tracking echocardiography is an independent prognostic marker for in-hospital events in patients with acute non-massive PE. Our results may help identify high-intermediate risk patients who need a closer monitoring.

Surgical as Opposed to Transcatheter Aortic Valve Replacement Improves Basal Interventricular Septal Hypertrophy.

BACKGROUND: Basal interventricular septum (IVS) hypertrophy (BSH) with reduced basal IVS contraction and IVS-aorta angle is frequently associated with aortic stenosis (AS). BSH shape suggests compression by the longitudinally elongated ascending aorta, causing basal IVS thickening and contractile dysfunction, further suggesting the possibility of aortic wall shortening to improve the BSH. Surgical aortic valve replacement (SAVR), as opposed to transcatheter AVR (TAVR), includes aortic wall shortening by incision and stitching on the wall and may potentially improve BSH. We hypothesized that BSH configuration and its contraction improves after SAVR in patients with AS. Methods and Results: In 32 patients with SAVR and 36 with TAVR for AS, regional wall thickness and systolic contraction (longitudinal strain) of 18 left ventricular (LV) segments, and IVS-aorta angle were measured on echocardiography. After SAVR, basal IVS/average LV wall thickness ratio, basal IVS strain, and IVS-aorta angle significantly improved (1.11±0.24 to 1.06±0.17; -6.2±5.7 to -9.1±5.2%; 115±22 to 123±14°, P<0.001, respectively). Contractile improvement in basal IVS was correlated with pre-SAVR BSH (basal IVS/average LV wall thickness ratio or IVS-aorta angle: r=0.47 and 0.49, P<0.01, respectively). In contrast, BSH indices did not improve after TAVR. CONCLUSIONS: In patients with AS, SAVR as opposed to TAVR improves associated BSH and its functional impairment.

The First Living-Donor Lobar Lung Transplantation in Korea: a Case Report.

Lung transplantation is the only treatment for end-stage lung disease, but the problem of donor shortage is unresolved issue. Herein, we report the first case of living-donor lobar lung transplantation (LDLLT) in Korea. A 19-year-old woman patient with idiopathic pulmonary artery hypertension received her father's right lower lobe and her mother's left lower lobe after pneumonectomy of both lungs in 2017. The patient has recovered well and is enjoying normal social activity. We think that LDLLT could be an alternative approach to deceased donor lung transplantation to overcome the shortage of lung donors.

Multimodal Biometric Recognition Based on Convolutional Neural Network by the Fusion of Finger-Vein and Finger Shape Using Near-Infrared (NIR) Camera Sensor.

Finger-vein recognition, which is one of the conventional biometrics, hinders fake attacks, is cheaper, and it features a higher level of user-convenience than other biometrics because it uses miniaturized devices. However, the recognition performance of finger-vein recognition methods may decrease due to a variety of factors, such as image misalignment that is caused by finger position changes during image acquisition or illumination variation caused by non-uniform near-infrared (NIR) light. To solve such problems, multimodal biometric systems that are able to simultaneously recognize both finger-veins and fingerprints have been researched. However, because the image-acquisition positions for finger-veins and fingerprints are different, not to mention that finger-vein images must be acquired in NIR light environments and fingerprints in visible light environments, either two sensors must be used, or the size of the image acquisition device must be enlarged. Hence, there are multimodal biometrics based on finger-veins and finger shapes. However, such methods recognize individuals that are based on handcrafted features, which present certain limitations in terms of performance improvement. To solve these problems, finger-vein and finger shape multimodal biometrics using near-infrared (NIR) light camera sensor based on a deep convolutional neural network (CNN) are proposed in this research. Experimental results obtained using two types of open databases, the Shandong University homologous multi-modal traits (SDUMLA-HMT) and the Hong Kong Polytechnic University Finger Image Database (version 1), revealed that the proposed method in the present study features superior performance to the conventional methods.

Convolutional Neural Network-Based Classification of Driver's Emotion during Aggressive and Smooth Driving Using Multi-Modal Camera Sensors.

Because aggressive driving often causes large-scale loss of life and property, techniques for advance detection of adverse driver emotional states have become important for the prevention of aggressive driving behaviors. Previous studies have primarily focused on systems for detecting aggressive driver emotion via smart-phone accelerometers and gyro-sensors, or they focused on methods of detecting physiological signals using electroencephalography (EEG) or electrocardiogram (ECG) sensors. Because EEG and ECG sensors cause discomfort to drivers and can be detached from the driver's body, it becomes difficult to focus on bio-signals to determine their emotional state. Gyro-sensors and accelerometers depend on the performance of GPS receivers and cannot be used in areas where GPS signals are blocked. Moreover, if driving on a mountain road with many quick turns, a driver's emotional state can easily be misrecognized as that of an aggressive driver. To resolve these problems, we propose a convolutional neural network (CNN)-based method of detecting emotion to identify aggressive driving using input images of the driver's face, obtained using near-infrared (NIR) light and thermal camera sensors. In this research, we conducted an experiment using our own database, which provides a high classification accuracy for detecting driver emotion leading to either aggressive or smooth (i.e., relaxed) driving. Our proposed method demonstrates better performance than existing methods.

Late outcome of percutaneous mitral commissurotomy: Randomized comparison of Inoue versus double-balloon technique.

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 25 years in a randomized trial. METHODS: Between 1989 and 1995, 302 patients (77 men, 41 ± 11 years) 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 20.7 years (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 24 years 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) <1.8 cm2 (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 25 years, and the achievement of effective commissurotomy to develop post-PMC commissural MR or immediate post-PMC MVA ≥1.8 cm2 is important in optimizing the late results of PMC.

Early surgery versus conventional treatment for infective endocarditis.

BACKGROUND: The timing and indications for surgical intervention to prevent systemic embolism in infective endocarditis remain controversial. We conducted a trial to compare clinical outcomes of early surgery and conventional treatment in patients with infective endocarditis. METHODS: We randomly assigned patients with left-sided infective endocarditis, severe valve disease, and large vegetations to early surgery (37 patients) or conventional treatment (39). The primary end point was a composite of in-hospital death and embolic events that occurred within 6 weeks after randomization. RESULTS: All the patients assigned to the early-surgery group underwent valve surgery within 48 hours after randomization, whereas 30 patients (77%) in the conventional-treatment group underwent surgery during the initial hospitalization (27 patients) or during follow-up (3). The primary end point occurred in 1 patient (3%) in the early-surgery group as compared with 9 (23%) in the conventional-treatment group (hazard ratio, 0.10; 95% confidence interval [CI], 0.01 to 0.82; P=0.03). There was no significant difference in all-cause mortality at 6 months in the early-surgery and conventional-treatment groups (3% and 5%, respectively; hazard ratio, 0.51; 95% CI, 0.05 to 5.66; P=0.59). The rate of the composite end point of death from any cause, embolic events, or recurrence of infective endocarditis at 6 months was 3% in the early-surgery group and 28% in the conventional-treatment group (hazard ratio, 0.08; 95% CI, 0.01 to 0.65; P=0.02). CONCLUSIONS: As compared with conventional treatment, early surgery in patients with infective endocarditis and large vegetations significantly reduced the composite end point of death from any cause and embolic events by effectively decreasing the risk of systemic embolism. (EASE ClinicalTrials.gov number, NCT00750373.).

Subprosthetic Pannus after Aortic Valve Replacement Surgery: Cardiac CT Findings and Clinical Features.

PURPOSE: To investigate the cardiac computed tomographic (CT) findings and clinical implications of subprosthetic pannus in patients who have undergone aortic valve replacement. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the need to obtain written informed consent was waived. From April 2011 to March 2012, 88 patients (mean age, 63 years; 45 men) with a prosthetic aortic valve who underwent cardiac CT were retrospectively selected. Dynamic cardiac CT images were analyzed by using a multiplanar reformatted technique. The presence or absence of subprosthetic pannus and its extent were evaluated at cardiac CT. The geometric orifice area and the effective orifice area of each prosthetic valve were measured to enable analysis of the pannus encroachment ratio in the systolic phase. Hemodynamic parameters at echocardiography, including mean transprosthetic pressure gradient (MTPG), were compared between patients with and those without pannus. The encroachment ratio and the MTPG were correlated by using the Spearman test to evaluate the relationship between the two variables. RESULTS: Seventeen patients (19%) had subprosthetic pannus at cardiac CT. In patients with subprosthetic pannus, MTPG, peak pressure gradient, transvalvular peak velocity, and left ventricular ejection fraction (LVEF) were significantly higher than in patients without pannus (MTPG: 28.1 mm Hg ± 19.8 [standard deviation] vs 14.0 mm Hg ± 6.5, P = .004; peak pressure gradient: 53.1 mm Hg ± 38.4 vs 26.1 mm Hg ± 11.4, P = .004; transvalvular peak velocity: 3.3 m/sec ± 1.3 vs 2.5 m/sec ± 0.5; and LVEF: 64.7% ± 7.4 vs 56.8% ± 10.5, P = .004). A high MTPG (≥40 mm Hg) was observed in four patients at echocardiography, and subprosthetic panni were identified at CT in all four patients. In patients with increased MTPGs, the encroachment ratio by subprosthetic pannus at CT was significantly higher than that in patients with MTPGs of less than 40 mm Hg (42.7 ± 13.3 vs 7.6 ± 3, P = .012). CONCLUSION: Cardiac CT revealed subprosthetic pannus to be a cause of the hemodynamic changes in patients who had undergone aortic valve replacement. By helping quantify the encroachment ratio by pannus, cardiac CT may help differentiate which subprosthetic panni might lead to substantial flow limitation over the prosthetic aortic valve.

Preoperative cardiac computed tomography for demonstration of congenital cardiac septal defect in adults.

OBJECTIVES: We aimed to evaluate the role of preoperative cardiac computed tomography (CT) for adults with congenital cardiac septal defect (CSD). METHODS: Sixty-five consecutive patients who underwent preoperative CT and surgery for CSD were included. The diagnostic accuracy of CT and the concordance rate of the subtype classification of CSD were evaluated using surgical findings as the reference standard. Sixty-five patients without CSD who underwent cardiac valve surgery were used as a control group. An incremental value of CT over echocardiography was described retrospectively. RESULTS: Sensitivity and specificity of CT for diagnosis of CSD were 95 % and 100 %, respectively. The concordance rate of subtype classification was 91 % in CT and 92 % in echocardiography. The maximum size of the defect measured by CT correlated well with surgical measurement (r = 0.82), and the limit of agreement was -0.9 ± 7.42 mm. In comparison with echocardiography, CT was able to detect combined abnormalities in three cases, and exclusively provided correct subtype classification or clarified suspected abnormal findings found on echocardiography in seven cases. CONCLUSIONS: Cardiac CT can accurately demonstrates CSD in preoperative adult patients. CT may have an incremental role in preoperative planning, particularly in those with more complex anatomy. KEY POINTS: • Cardiac CT can demonstrate cardiac septal defect accurately in preoperative planning. • Cardiac CT can demonstrate combined abnormalities of cardiac septal defect. • Cardiac CT may have an incremental role over echocardiography in complex anatomy.

Fate of atrioventricular valve function of the transplanted heart.

BACKGROUND: Long-term echocardiographic data on quantitative assessment of tricuspid and mitral regurgitation after heart transplantation are scarce. METHODS AND RESULTS: From November 1992 to December 2008, the medical records for 201 patients (mean age, 42.8±12.4 years, 47 females) who underwent heart transplantation were reviewed. Quantitative assessment of mitral and tricuspid valve function was performed using transthoracic echocardiography through long-term follow-up. A total of 196 (97.5%) patients were evaluated with echocardiography for more than 6 months postoperatively. During a mean echocardiography follow-up duration of 89.9±54.3 months, 23 (11.4%) patients showed either tricuspid regurgitation (TR >mild; n=21, 10.4%) or mitral regurgitation (MR >mild; n=6, 3.0%); 4 (2.0%) patients experienced both significant TR and MR. Freedom from moderate-to-severe TR at 10 years was 85.5±5.1% and 93.4±2.2% for the standard and bicaval techniques, respectively (P=0.531). Freedom from moderate-to-severe MR at 10 years was 96.0±2.7% and 98.6±1.0%, respectively, for the 2 techniques (P=0.252). In multivariate analysis, older-age donor emerged as the only independent predictor of significant TR (hazard ratio 1.06, 95% confidence interval 1.01-1.12, P=0.012). CONCLUSIONS: The long-term results of atrioventricular function after heart transplantation in adults were excellent regardless of anastomotic technique. Older-age donor was significantly associated with the development of postoperative TR.

Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Significant Tricuspid Regurgitation.

BACKGROUND: There are limited data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation with significant tricuspid regurgitation (TR), which can lead to hepatic dysfunction and intestinal malabsorption. We aimed to compare the efficacy and safety of DOACs and warfarin for patients with atrial fibrillation with significant (moderate to severe) TR. METHODS AND RESULTS: A total of 1215 patients with significant TR and atrial fibrillation who were treated with warfarin (N=491) or DOACs (N=724) were retrospectively analyzed. The primary outcomes were ischemic stroke, systemic embolic events, and hospitalization for major bleeding. The secondary outcomes were intracranial hemorrhage, hospitalization for gastrointestinal bleeding, all-cause mortality, and a composite outcome. The median follow-up duration was 2.4 years. In the inverse probability treatment weighting-adjusted cohort, DOACs and warfarin had a similar risk for ischemic stroke and systemic embolic events (adjusted hazard ratio [aHR], 0.95 [95% CI, 0.67-1.36]; P=0.79) and major bleeding (aHR, 0.78 [95% CI, 0.57-1.06]; P=0.11). For the secondary outcomes, relative to warfarin, DOACs had a lower risk of intracranial hemorrhage and the composite outcome, and a comparable risk for gastrointestinal bleeding and all-cause mortality. In the subgroup analysis, the effects of DOACs on ischemic stroke and systemic embolic events were comparable to the effects of warfarin, even in patients with inferior vena cava plethora (increased right atrial pressure) or severe TR. CONCLUSIONS: In this study, relative to warfarin, DOACs demonstrated comparable efficacy for ischemic stroke and systemic embolic events and major bleeding, with a lower intracranial hemorrhage risk in patients with significant TR and atrial fibrillation, indicating their effectiveness and safety.

Determination of mitomycin C in rat plasma by liquid chromatography-tandem mass spectrometry and its application for determining pharmacokinetics in rat.

To develop the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring mitomycin C in rat plasma, samples were processed using solid-phase extraction, with the internal standard being carbamazepine. A reversed phased C18 column was utilized for the LC-MS/MS study, and mobile phases consisting of 0.1 % formic acid in acetonitrile and water were injected into it at a rate of 0.3 mL/min. Multiple reaction monitoring in positive-ion mode with precursor-product ion pairs 335.3 â†’ 242.3 (mitomycin C) and 237.1 â†’ 194.1 (carbamazepine) was employed to quantify the compounds. The linear range in plasma was found to be 10-4000 ng/mL (r2 = 0.992). The inter-batch and intra-batch precision were <14.3 % (LLOQ: 14.7 %) and 13.4 % (LLOQ: 16.1 %), respectively. The recovery and the matrix effect of mitomycin C in plasma were 113 % and 111 %, respectively. Mitomycin C was stable under the conditions of this assay method. In the end, this approach proved effective in a pharmacokinetic investigation with the intravenous and oral administration of mitomycin C to rats.

Diagnostic Performance of Perfusion-Only SPECT/CT for Chronic Thromboembolic Pulmonary Hypertension in Comparison With Ventilation-Perfusion Planar, SPECT, and SPECT/CT Imaging.

PURPOSE: The aim of this study was to assess the diagnostic performance of perfusion-only SPECT/CT (Q SPECT/CT) in comparison with that of ventilation/perfusion planar scintigraphy (V/Q planar), perfusion SPECT with ventilation scan (V/Q SPECT), and perfusion SPECT/CT with ventilation scan (V/Q SPECT/CT) in chronic thromboembolic pulmonary hypertension (CTEPH). PATIENTS AND METHODS: Patients with pulmonary hypertension who underwent ventilation-perfusion planar and SPECT/CT were retrospectively recruited. Two nuclear medicine physicians interpreted V/Q planar, V/Q SPECT, V/Q SPECT/CT, and Q SPECT/CT according to the European Association of Nuclear Medicine criteria. The diagnostic accuracy of these modalities for CTEPH was compared using a composite reference standard of pulmonary angiography, imaging test, cardiorespiratory assessment, and follow-up. RESULTS: A total of 192 patients were enrolled, including 85 with CTEPH. The sensitivity of Q SPECT/CT was 98.8%, which similar to that of V/Q planar (97.6%), V/Q SPECT (96.5%), or V/Q SPECT/CT (100.0%). In contrast, Q SPECT/CT exhibited significantly lower specificity (73.8%) compared with V/Q planar (86.9%, P = 0.001), V/Q SPECT (87.9%, P < 0.001), and V/Q SPECT/CT (88.8%, P < 0.001). The significantly lower specificity of Q SPECT/CT, compared with the 3 others, was observed in the subgroup aged ≥50 years ( P < 0.001 for all), but not in those <50 years. CONCLUSIONS: Q SPECT/CT exhibited lower specificity compared with V/Q planar, V/Q SPECT, and V/Q SPECT/CT in diagnosing CTEPH. It might underscore the essential role of a ventilation scan in patients with PH, even with the introduction of SPECT/CT.