Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Oral Porphyromonas gingivalis infection affects intestinal microbiota and promotes atherosclerosis.

AIM: The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative effects of oral infection with Porphyromonas gingivalis (PG), the major pathogen for periodontitis, on intestinal microbiota and atherosclerosis. MATERIALS AND METHODS: ApoE-/- mice were fed a normal chow diet (NC), a Western diet (WD) or a WD with oral PG infection (PG). The PG infection was investigated by placing a total of 109 CFUs of live PG into the oral cavity of each mouse using a feeding needle five times a week for 3 weeks. Atherosclerotic lesions of the aortae were measured, and blood lipoproteins and the expression of molecules related to lipid metabolism in the liver were analysed. We also performed 16S RNA sequencing and a microbiome analysis using faeces. RESULTS: En face bloc preparation of the aortae showed that the PG group had a 1.7-fold increase in atherosclerotic lesions compared with the WD group (p < .01). Serum analyses showed that oral PG infection induced a significant decrease in high-density lipoprotein (HDL) and triglyceride. Western blots of hepatic tissue lysates revealed that PG infection reduced the expression of scavenger receptor class B type 1 (SR-B1) in the liver by 50%. Faecal microbiota analysis revealed that species richness estimates (Chao1, ACE) decreased immediately after PG infection. PG infection also induced a significant decrease in Shannon diversity and an increase in Simpson's indices in the WD-fed mice. PG infection significantly increased the phyla Actinobacteria and Deferribacteres, along with the species Mucispirillum schaedleri and Lactobacillus gasseri, in the mice. The functional study showed that PG infection increased the expression of proteins that function in carbohydrate and glucose metabolism, including phosphotransferase system (PTS) proteins and the GntR family transcriptional regulator. CONCLUSIONS: Oral PG infection promotes atherosclerosis and induces significant metabolic changes, including reduced serum HDL and reduced hepatic SR-B1 and ABCA1 expression, as well as changes in intestinal microbiota. Our study suggests that intestinal dysbiosis accompanies periodontitis and could play a role in atherosclerosis.

Predictors of Subsequent Heart Failure After Left Atrial Appendage Closure.

BACKGROUND: Left atrial appendage occlusion (LAAO) plays an important role in preventing stroke in patients with atrial fibrillation. However, LAAO may interact unfavorably with left atrial (LA) compliance and reservoir function and thus increase the risk of heart failure (HF). The purpose of this study was to identify predictors of subsequent HF after successful LAAO.Methods and Results: A total of 98 patients (mean age 70±9 years, 68% male) who had undergone LAAO were included. The primary endpoint was unexpected HF admission after LAAO. During a mean period of 36±26 months, 16 of the 98 patients (16%) experienced hospital HF admission. In multivariate analysis, higher E/e' (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.02-1.20, P=0.014), higher left ventricular mass index (HR 1.02, 95% CI 1.00-1.03, P=0.023), history of HF (HR 4.78, 95% CI 1.55-14.7, P=0.006), and lower LA strain (HR 0.80, 95% CI 0.70-0.93, P=0.003) were independently associated with hospital HF admission. Patients with LAAO had a significantly higher incidence of subsequent HF than the control group after propensity score matching (P=0.046). CONCLUSIONS: LAAO increases the occurrence of HF, and it is not uncommon after successful LAAO. A previous history of HF, left ventricular mass index, E/e', and abnormal LA strain are independently associated with the development of HF. These parameters should be considered before attempting LAAO.

Discrepancy of Aortic Valve Area Measurements by Doppler vs. Biplane Stroke Volume Measurements and Utility of Combining the Different Areas in Aortic Valve Stenosis　- The Asian Valve Registry.

BACKGROUND: The aortic valve area index (AVAI) in aortic stenosis (AS) is measured by echocardiography with a continuity equation using the stroke volume index by Doppler (SVIDoppler) or biplane Simpson (SVIBiplane) method. AVAIDopplerand AVAIBiplaneoften show discrepancy due to differences between SVIDopplerand SVIBiplane. The degree of discrepancy and utility of combined AVAIs have not been investigated in a large population of AS patients, and the characteristics of subjects with larger discrepancies are unknown.Methods and Results:We studied 820 patients with significant AS (AVADoppler<1.5 cm2) enrolled in the Asian Valve Registry, a prospective multicenter registry at 12 Asian centers. All-cause death and aortic valve replacement were defined as events. SVIDopplerwas significantly larger than SVIBiplane(49±11 vs. 39±11 mL/m2, P<0.01) and AVAIDopplerwas larger than AVAIBiplane(0.51±0.15 vs. 0.41±0.14 cm2/m2, P<0.01). An increase in (AVAIDoppler- AVAIBiplane) correlated with shorter height, lower weight, older age, smaller left ventricular (LV) diameter and increased velocity of ejection flow at the LV outflow tract. Severe AS by AVAIDoppleror AVAIBiplaneenabled prediction of events, and combining these AVAIs improved the predictive value of each. CONCLUSIONS: Discrepancy in AVAI by Doppler vs. biplane method was significantly more pronounced with increased LV outflow tract flow velocity, shorter height, lower weight, older age and smaller LV cavity dimensions. Combining the AVAIs enabled mutual and incremental value in predicting events.

Stroke Outcomes in the COMPASS Trial.

BACKGROUND: Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies). We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups. METHODS: Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152). Patients who required anticoagulation or had a stroke within 1 month, previous lacunar stroke, or intracerebral hemorrhage were excluded. RESULTS: During a mean follow-up of 23 months, fewer patients had strokes in the rivaroxaban plus aspirin group than in the aspirin group (83 [0.9% per year] versus 142 [1.6% per year]; hazard ratio [HR], 0.58; 95% CI, 0.44-0.76; P<0.0001). Ischemic/uncertain strokes were reduced by nearly half (68 [0.7% per year] versus 132 [1.4% per year]; HR, 0.51; 95% CI, 0.38-0.68; P<0.0001) by the combination in comparison with aspirin. No significant difference was noted in the occurrence of stroke in the rivaroxaban alone group in comparison with aspirin: annualized rate of 0.7% (HR, 0.82; 95% CI, 0.65-1.05). The occurrence of fatal and disabling stroke (modified Rankin Scale, 3-6) was decreased by the combination (32 [0.3% per year] versus 55 [0.6% per year]; HR, 0.58; 95% CI, 0.37-0.89; P=0.01). Independent predictors of stroke were prior stroke, hypertension, systolic blood pressure at baseline, age, diabetes mellitus, and Asian ethnicity. Prior stroke was the strongest predictor of incident stroke (HR, 3.63; 95% CI, 2.65-4.97; P<0.0001) and was associated with a 3.4% per year rate of stroke recurrence on aspirin. The effect of the combination in comparison with aspirin was consistent across subgroups with high stroke risk, including those with prior stroke. CONCLUSIONS: Low-dose rivaroxaban plus aspirin is an important new antithrombotic option for primary and secondary stroke prevention in patients with clinical atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.

Clinical features differentiating Takotsubo cardiomyopathy in the peripartum period from peripartum cardiomyopathy.

There are some similarities in clinical features between Takotsubo cardiomyopathy during the peripartum period (PTCM) and peripartum cardiomyopathy (PPCM). Both conditions present as acute heart failure and decreased left ventricular (LV) ejection fraction in the peripartum period in previously heart-healthy women. The present study aimed to evaluate the differences in clinical features and outcomes between PTCM and PPCM. Between January 2004 and December 2016, 37 consecutive patients who demonstrated LV dysfunction during the peripartum period without previous heart disease were recruited retrospectively. The clinical, laboratory, and echocardiographic data of these patients were comprehensively reviewed. Twenty-one (57%) and 16 (43%) patients were classified into PPCM and PTCM groups, respectively, based on echocardiographic findings. The initial LV ejection fraction did not differ significantly between the 2 groups. However, all patients with PTCM showed complete recovery of LV ejection fraction at the 1-month follow-up. However, among 20 patients with PPCM who underwent 1-month echocardiography, only 6 (30%) showed complete recovery of LV ejection fraction at the 1-month follow-up. At the 12-month follow-up, only 10 patients showed complete recovery of LV ejection fraction. The incidence of PTCM was much higher than expected. Although LV dysfunction was similar at the initial diagnosis, the prognosis of LV recovery was more favorable in PTCM than in PPCM. Therefore, physicians should differentiate these two diseases entities, although they have several similarities in acute LV dysfunction.

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.

Differences in Flow-Gradient Patterns Between Severe Bicuspid Aortic Stenosis and Severe Tricuspid Aortic Stenosis　- Mechanistic Insight From Multimodal Imaging.

BACKGROUND: We investigated the flow-gradient pattern characteristics and associated factors in severe bicuspid aortic stenosis (AS) compared with severe tricuspid AS.Methods and Results:A total of 252 patients with severe AS (115 bicuspid vs. 137 tricuspid) who underwent aortic valve (AV) replacement were retrospectively analyzed. Patients were classified into 4 groups according to stroke volume index and mean pressure gradient across the AV [normal-flow-high-gradient (NF-HG), low-flow-high-gradient, normal-flow-low-gradient, low-flow-low-gradient (LF-LG)]. In 89 patients who underwent cardiac computed tomography (CT), influential structural parameters of the left ventricular outflow tract (LVOT), AV and ascending aorta were assessed. Bicuspid AS was more likely to present a NF-HG pattern (83.5% vs. 64.2%, P<0.001), and significantly fewer presented a LF-LG pattern compared with tricuspid AS. In bicuspid AS, there was a significant mismatch between geometric orifice area (GOA) on CT planimetry and effective orifice area (EOA) calculated using the echocardiographic continuity equation. Bicuspid AS presented with a larger angle between the LVOT-AV and aorta. Multivariate analysis of bicuspid AS revealed that systemic arterial compliance (ß=-0.350, P=0.031) and the LVOT-AV-aorta angle (ß=-0.538, P=0.001), and stroke volume index (ß=0.409, P=0.008) were associated with a discrepancy between GOA and EOA. CONCLUSIONS: Flow-gradient patterns in bicuspid AS differ from those of tricuspid AS and are associated with the structural and functional characteristics of the aorta.

Infective Endocarditis in Cancer Patients　- Causative Organisms, Predisposing Procedures, and Prognosis Differ From Infective Endocarditis in Non-Cancer Patients.

BACKGROUND: Infective endocarditis (IE) in cancer patients is increasing, but because little is known about it in these patients, we analyzed patient characteristics and outcomes and compared these factors in IE patients with and without cancer. Methods and Results: This retrospective cohort study included 170 patients with IE newly diagnosed between January 2011 and December 2015. Among 170 patients, 30 (17.6%) had active cancer. The median age of IE patients with cancer was higher than that of non-cancer patients. Nosocomial IE was more common in cancer patients. Non-dental procedures, such as intravenous catheter insertion and invasive endoscopic or genitourinary procedures, were more frequently performed before IE developed in cancer patients. Staphylococcus was the most common pathogen in cancer patients, whereas Streptococcus was the most common in non-cancer patients. In-hospital mortality was significantly higher in cancer patients with IE (34.4% vs. 12.4%, P<0.001). IE was an important reason for discontinuing antitumor therapy and withholding additional aggressive treatment in nearly all deceased cancer patients. CONCLUSIONS: IE is common in cancer patients and is associated with poorer outcomes. Patients with IE and cancer have different clinical characteristics. Additional studies regarding antibiotic prophylaxis before non-dental invasive procedures in cancer patients are needed, as cancer patients are not considered to be at higher risk of IE.