Impact of left ventricular diastolic function and direct oral anticoagulant use for predicting embolic events in patients with heart failure and atrial fibrillation.

Background: Patients with atrial fibrillation (AF) and heart failure (HF) have high stroke risk owing to left atrial dysfunction. However, anticoagulation is a concern in patients with high bleeding risk. We aimed to identify independent predictors of stroke in HF patients with AF. Methods: We retrospectively examined 320 patients (mean age 79 ± 12 years, 163 women) hospitalized with acute HF complicated by AF between January 2014 and December 2018. Patients were followed from admission until ischemic stroke or systemic embolism (SSE) onset or death or were censored at the last contact date or September 2023. Results: SSE occurred in 40 patients (median follow-up of 528 days). Multivariate Cox regression analysis identified age (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.00-1.07, p = .034), direct oral anticoagulant (DOAC) use (HR 0.26, 95% CI 0.11-0.60, p = .002), and early diastolic peak flow velocity to early diastolic peak annular velocity (E/e'; HR 1.05, 95% CI 1.02-1.08, p < .001) to be independent predictors of SSE, whereas left atrial reservoir strain was not. After determining an appropriate E/e' cutoff by receiver-operating characteristic curve analysis and adjusting the multivariate Cox model, E/e' ≥17.5 (HR 3.30, 95% CI 1.56-6.83, p = .001) independently predicted SSE. The results were consistent with no interaction in the subanalysis except for gender. Conclusion: Elderly patients not on DOACs with elevated E/e' may be at higher risk of stroke, suggesting that DOACs should be the first choice for patients with elevated E/e' and aggressive additional prophylaxis and careful follow-up are needed.

A Surviving Case of Myocardial Infarction with Ventricular Septal Rupture and Ventricular Aneurysm following Gastrointestinal Bleeding.

A 55-year-old man presented to the emergency department with worsening shortness of breath 1 month after a gastrointestinal bleed. He had congestive heart failure, and an electrocardiogram suggested ischemic heart disease involvement. Echocardiography revealed a ventricular septal defect complicated by a left ventricular aneurysm in the inferior-posterior wall. Conservative treatment was started, but hemodynamic collapse occurred on the third day of admission and coronary angiography revealed a revascularizing lesion in the right fourth posterior descending coronary artery. Subsequently, his hemodynamic status continued to deteriorate, even with an Impella CP® heart pump, so ventricular septal defect patch closure and left ventricular aneurysm suture were performed. His condition improved and he was discharged on day 23 of admission and was not readmitted within 6 months after the procedure. Hemodynamic management of ventricular septal defects requires devices that reduce afterload, and clinicians should be aware of the risk of myocardial infarction after gastrointestinal bleeding.

Prognostic Impact of Left Atrial Strain in Patients Hospitalized for Acute Heart Failure With Atrial Fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) and heart failure (HF) have elevated left ventricular end-diastolic pressure in addition to decreased left atrial (LA) function, but there are few reports of useful prognostic indices that can be seen on echocardiography. In this study, we investigated the association between LA reservoir strain (LARS) and prognosis in this group of patients.Methods and Results: We retrospectively enrolled patients with acute HF complicated by AF who were consecutively admitted to hospital between January 2014 and December 2018. A total of 320 patients (mean age 79±12 years, 163 women) were included in the analysis. During a median follow-up of 473 days, 92 cardiovascular deaths and 113 all-cause deaths occurred. In the multivariate analysis, LARS was an independent predictor of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.99, P=0.016). Multivariate analysis also showed that the patients in the lowest LARS tertile (<7.16%) had a significantly increased risk of cardiovascular death (HR 1.76, 95% CI 1.05-2.96; P=0.033) and all-cause death (HR 1.90, 95% CI 1.17-3.08; P=0.009) in comparison with patients in the highest LARS tertile (>10.52%). CONCLUSIONS: We found a significant association between LARS and death in patients with AF and HF. Patients with reduced LARS had poor prognosis, suggesting the need for aggressive therapy to improve their LA dysfunction.

Relation between laxative use and risk of major bleeding in patients with atrial fibrillation and heart failure.

Constipation has been reported to increase the risk of cardiovascular mortality. Patients with atrial fibrillation (AF) and heart failure (HF) have more comorbidities and an increased bleeding risk. However, it remains unclear whether constipation is associated with an increased risk of incident bleeding complications in AF with HF. Here, we investigated the association between constipation requiring laxatives and major bleeding in AF and HF. We retrospectively analyzed the medical records of 370 consecutive patients hospitalized for AF and congestive HF. Constipation was defined as regularly taking laxatives or having at least two prescriptions for a ≥ 30-day supply of laxatives. Sixty patients experienced major bleeding events during a median follow-up of 318 days. The most common sites of bleeding were lower gastrointestinal (28%, 17/60), upper gastrointestinal (27%, 16/60), and intracranial (20%, 12/60). There were 33 (55%) patients with constipation in the bleeding group and 107 (35%) in the non-bleeding group (P = 0.004). Multivariate Cox regression analysis adjusted for HAS-BLED score, hemoglobin, and direct oral anticoagulant use showed that constipation (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.11-3.08; p = 0.019) was a significant risk factor for major bleeding. We found a significant association between constipation requiring laxatives and major bleeding in patients with AF and HF. These findings indicate the need for constipation prevention in these patients to avoid reliance on invasive defecation management, including laxatives.

Venous thromboembolism is caused by prothrombin p.Arg541Trp mutation in Japanese individuals.

Venous thromboembolism (VTE) is a multifactorial disease. Because low-frequency variants and rare mutations have been found to predispose carriers toward VTE, there is a need for variant discovery in clinical settings. Therefore, we used a whole-exome approach for a young VTE patient with a positive family history. We identified in the proband and his affected mother a rare, functional missense variant of prothrombin, p.Arg541Trp, which contributes to the clinical picture of VTE.

Thoracic endovascular repair for disseminated intravascular coagulation associated with chronic type B aortic dissection.

OBJECTIVES: Chronic disseminated intravascular coagulation is a rare complication of aortic dissection, and its optimal treatment remains controversial. METHODS: We present a 78-year-old man with repeated hemorrhagic events by disseminated intravascular coagulation due to chronic aortic dissection treated by thoracic endovascular aortic repair. RESULTS: Computed tomography angiography at three months revealed a completely thrombosed false lumen from the distal aortic arch to the descending aorta at the celiac artery level. Platelets and D-dimer levels remained stable, and the patient was doing well without hemorrhagic complications. CONCLUSIONS: Endovascular repair was effective for disseminated intravascular coagulation due to chronic type B aortic dissection.

1α,25-Dihydroxyvitamin D3 enhances TRPV6 transcription through p38 MAPK activation and GADD45 expression.

The active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], acts as a ligand for the vitamin D receptor (VDR), and regulates various physiological processes, including calcium and bone metabolism, cellular growth and differentiation, immunity and cardiovascular function. A number of vitamin D derivatives have been synthesized for the treatment of cancer and inflammatory disease, but the adverse effect of hypercalcemic activity due to intestinal calcium absorption has limited wide clinical application. The VDR target gene product TRPV6 is essential for intestinal calcium absorption. Our prior study has demonstrated that 1,25(OH)2D3 induces TRPV6 mRNA expression at lower concentrations than for induction of CYP24A1, a VDR target gene involved in vitamin D inactivation, in intestinal SW480 cells, suggesting an additional mechanism for vitamin D signaling on TRPV6 induction. By searching for a signal transduction pathway involved in 1,25(OH)2D3-induced expression of TRPV6, we found that a p38 mitogen-activated protein kinase (MAPK) inhibitor reduces the expression of TRPV6 but not CYP24A1 in 1,25(OH)2D3-treated SW480 cells. Knockdown experiments showed that p38α is involved in 1,25(OH)2D3-induced expression of TRPV6 but not CYP24A1. Treatment with a de novo protein synthesis inhibitor suppressed 1,25(OH)2D3-induced TRPV6 expression. Finally, we found that 1,25(OH)2D3 treatment induced expression of GADD45A, which encodes the GADD45α MAPK kinase kinase activator, earlier than TRPV6 expression and that GADD45A knockdown reduced TRPV6 induction by 1,25(OH)2D3. These findings indicate that p38α and GADD45α are involved in an enhanced vitamin D signaling on TRPV6 expression.

Outcomes of limited proximal aortic replacement for type A aortic dissection in octogenarians.

OBJECTIVE: The number of older patients with acute aortic dissection type A (AAD [A]) is increasing as the population ages. We evaluated clinical outcomes for octogenarians with AAD (A) treated surgically at our hospital. Whenever possible, we limited the replacement site of the ascending aorta to the supracoronary and hemiarch. METHODS: Of 436 patients with AAD (A) seen in our hospital emergency room between April 2001 and August 2015, 90 were octogenarians. Surgery was performed using a simple cardiopulmonary bypass established through the right femoral artery and venous cannulation, and distal anastomosis was performed under deep hypothermic circulatory arrest at 20°C. RESULTS: Of the 90 octogenarians with AAD (A), 11 required cardiopulmonary resuscitation, 9 of whom died. Four patients with stable hemodynamics refused surgery. Thus, 77 were treated surgically. Of these 77 patients, isolated replacement of the ascending aorta or hemiarch was performed in 73 (94.8%), and total arch replacement in 4 (5.2%). Five patients (6.5%) died within 30 days, and 5 (6.5%) died in the hospital more than 30 days after surgery. Seven (9.1%) had a new stroke, 5 (6.5%) had pneumonia, and 4 (5.2%) had mediastinitis. Forty-four (57.1%) patients were discharged to their homes and 23 (30%) to rehabilitation hospitals. Three patients later required endovascular stent graft repair, which was successful in each case. The overall postoperative survival was 82%, 70%, and 62% at 1, 3, and 5 years, respectively. CONCLUSIONS: Our results suggest that our limited replacement protocol for emergency AAD (A) surgery has early and midterm survival benefits for octogenarians.