Background: Perioperative management of body fluid levels after cardiovascular surgery with cardiopulmonary bypass is essential. Fluid management using tolvaptan with conventional diuretics is effective in maintaining urine output without worsening renal function. This study aimed to improve the in-out balance in the early perioperative phase using low-dose tolvaptan (3.75 mg/day).

Methods and Results: This prospective, single-center, randomized, open-label study included 199 patients who underwent cardiovascular surgery with cardiopulmonary bypass in Kobe City Medical Center General Hospital between September 2018 and December 2020. Treatment with tolvaptan and loop diuretics (tolvaptan group; 99 patients) was compared with treatment with loop diuretics alone (control group; 100 patients) to evaluate achievement of preoperative body weight as the primary outcome. Secondary outcomes were urine volume, the incidence of worsening renal function (WRF), and postoperative paroxysmal atrial fibrillation (POAF). There was no significant difference between groups in the return to preoperative body weight on postoperative Day 6. The tolvaptan group had significantly increased urine volume (2,530 vs. 2,150 mL/day) and decreased total furosemide dose (24 vs. 32 mg) compared with the control group. No significant differences were observed in the development of WRF and POAF between the 2 groups.

Conclusions: Although low-dose tolvaptan administration did not shorten the time to achieving preoperative body weight, it did significantly increase urine volume without WRF and POAF.

Background: Cardiogenic unilateral pulmonary edema (UPE) has been reported as an unusual condition and to occur in association with severe mitral regurgitation (MR). However, the prevalence of UPE in patients with severe MR remains unknown.

Methods and Results: Among 143 consecutive patients with chordal rupture and significant MR, 38 patients with acute severe MR were studied. The prevalence of UPE was 50% (19 patients); all these patients had right-sided UPE. Eight (21%) patients had bilateral pulmonary edema (BPE). All 8 patients with BPE and 18 of 19 patients with UPE had chordal rupture of the posterior leaflet. All patients with UPE and BPE had severe MR with similar left atrial size. Chest radiographs taken ≤48 h from symptom onset diagnosed UPE in 15 of 19 (79%) patients and BPE in 3 of 8 (38%) patients (P=0.037). Chest radiographs taken >48 h from symptom onset diagnosed UPE in 4 (21%) patients and BPE in 5 (62%) patients (P=0.037).

Conclusions: The prevalence of UPE was estimated as 50%; it was most frequently right sided and almost always associated with chordal rupture of the posterior leaflet. UPE is not rare, but common, particularly shortly after the development of acute severe MR caused by chordal rupture.

Background: The Kumamoto criteria have been proposed as a non-invasive screen for transthyretin amyloid cardiomyopathy. This study assessed the validity of the Kumamoto criteria externally.

Methods and Results: The study included 138 patients (median age 73 years; 65% male) who underwent ^{99 m}Tc-pyrophosphate (PYP) scintigraphy. Patients were divided into 4 groups according to total scores on the Kumamoto criteria (i.e., 0–3) for the following 3 factors: high-sensitivity cardiac troponin T ≥0.0308 ng/mL, wide (≥120 ms) QRS, and left ventricular posterior wall thickness ≥13.6 mm. The diagnostic performance and positive predictive value (PPV) of the Kumamoto criteria for positive ^{99 m}Tc-PYP scintigraphy were validated. Eighteen (13%) patients were positive on ^{99 m}Tc-PYP scintigraphy. The Kumamoto criteria had a favorable diagnostic performance (area under the curve 0.808). The PPV for groups with scores of 0, 1, 2, and 3 was 0% (n=0/42), 11% (n=6/57), 21% (n=7/33), and 83% (n=5/6), respectively, which is lower, particularly for those with a score of 2, than in the original Kumamoto cohort. However, the PPV increased after combining the Kumamoto criteria with a history of orthopedic diseases (spinal canal stenosis and/or carpal tunnel syndrome).

Conclusions: This study suggests that the Kumamoto criteria have a favorable diagnostic performance; however, the PPV may decrease depending on the study population. Combining the Kumamoto criteria with the presence of orthopedic disease may improve the PPV.

Background: Post hoc analysis of the PARADIGM-HF trial showed that sacubitril/valsartan (S/V) was more effective than enalapril in lowering HbA1c in patients with heart failure and diabetes.

Methods and Results: In the present study, the effect of S/V on glycemic control was retrospectively analyzed in 150 patients (median age 74 years) who were prescribed S/V for the treatment of heart failure and/or hypertension. After a median period of 13 weeks treatment, mean (±SD) HbA1c levels decreased significantly from 6.56±0.68% to 6.49±0.63%. The decrease in HbA1c was evident in patients with (n=111), but not in those without, diabetes. There were no significant changes in renal function after S/V treatment, but systolic blood pressure was significantly reduced from 141±21 to 134±19 mmHg. Ninety patients had N-terminal pro B-type natriuretic peptide (NT-proBNP) tested, and S/V significantly decreased median NT-proBNP concentrations from 1,026 to 618 pg/mL; however, there was no correlation between the degree of decrease in HbA1c and that in NT-proBNP. Multiple regression analysis revealed that being diabetic, rather than having heart failure, was a significant independent variable for a reduction in HbA1c.

Conclusions: Treatment with S/V improved glycemic control in patients with heart failure and/or hypertension, especially in those with concomitant diabetes. This favorable effect on glucose metabolism may be mediated by neprilysin inhibition and is desirable in the treatment of heart failure and hypertension in diabetic patients.

Background: Cardiovascular disease (CVD) screening entails precise event prediction to orient risk stratification, resource allocation, and insurance policy. We used random survival forests (RSF) to identify markers of incident CVD among Japanese adults enrolled in an employer-mandated screening program.

Methods and Results: We examined biomarker, health history, medication use, and lifestyle data from 155,108 adults aged ≥40 years. The occurrence of coronary artery disease (CAD) or atherosclerotic CVD (ASCVD) events was examined over 6 years of follow-up. The analysis used RSF to identify predictors, then investigated simplified RSF models with fewer predictors for individual-level risk prediction. Data were split into training (70%) and test (30%) datasets. At baseline, the median patient age was 47 years (interquartile range 41–56 years), with 65% males. In all, 1,642 CAD and 2,164 ASCVD events were observed. RSF identified history of heart disease, age, self-reported blood pressure medication, HbA1c, fasting blood sugar, and high-density lipoprotein as important markers of both endpoints. RSF analyses with only the top 20 predictors demonstrated good performance, with areas under the curve of >84% for CAD and >82% for ASCVD in test data across 6 years.

Conclusions: We present a machine learning technique for accurate assessment of cardiovascular risk using employer-mandated annual health checkup information. The algorithm produces individual-level risk curves over time, empowering clinicians to efficiently implement prevention strategies in a low-risk population.

Background: Recent major randomized trials revealed the superiority of non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) from 6 months to 2 years after percutaneous coronary intervention (PCI). However, whether NOAC monotherapy superiority over warfarin continues in real-world patients with a history of atrial fibrillation (AF), coronary stenting, and underlying chronic kidney disease (CKD) >1 year after PCI (e.g., at 5 years) has not been established.

Methods and Results: In the Rivaroxaban Estimation with Warfarin in Atrial Fibrillation Patients with Coronary Stent Implantation (REWRAPS) study (NCT02024230), a multicenter, prospective, non-randomized, open-label, physician-initiated efficacy and safety study in Japan, 493 patients received either rivaroxaban or warfarin. The primary efficacy endpoint was major adverse cardiac and cerebrovascular events (MACCE), consisting of cardiac and stroke death, non-fatal myocardial infarction, non-fatal stroke, systemic embolism, and coronary revascularization. The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium 3 and 5). The primary composite endpoint was net adverse clinical events (NACE), defined as a combination of all-cause death and major bleeding.

Conclusions: Completion of REWRAPS will provide, for the first time, evidence as to whether rivaroxaban is superior or non-inferior to warfarin with regard to the primary efficacy (MACCE), safety (major bleeding), or combined (all-cause death, major bleeding) endpoints in real-world patients with AF, coronary stenting, and underlying CKD an average of 5 years after PCI.