Development and validation of a bleeding risk prediction score for patients with mitral valve stenosis and atrial fibrillation or mechanical heart valves receiving long-term warfarin therapy.

AIMS: This study aimed to develop and validate a new bleeding risk score to predict warfarin-associated major bleeding for patients with mitral valve stenosis with atrial fibrillation (MSAF) or mechanical heart valves (MHV). METHODS: A multicentre, retrospective cohort study was conducted at 3 hospitals in Thailand. Adult patients with MSAF or MHV receiving warfarin for ≥3 months during 2011-2015 were identified. Data collection and case validation were performed electronically and manually. Potential variables were screened using the least absolute shrinkage and selection operator. Multivariate logistic regression analysis using stepwise backward selection was used to construct a risk score. Predictive discrimination of the score was evaluated using the C-statistic. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: There were 1287 patients (3903.41 patient-year of follow-up), with 192 experiencing bleeding (4.92 event/100 patient-year) in the derivation cohort. A new bleeding risk score termed, the HEARTS-60 + 3 score (hypertension/history of bleeding; external factors, e.g., alcohol/drugs [aspirin or nonsteroidal anti-inflammatory drugs]; anaemia/hypoalbuminaemia; renal/hepatic insufficiency; time in therapeutic range of <60%; stroke; age ≥60 y; target international normalized ratio of 3.0 [2.5-3.5]), was developed and showed good predictive performance (C-statistic [95% confidence interval] of 0.88 [0.85-0.91]). In the external validation cohort of 832 patients (2018.45 patient-year with a bleeding rate of 4.31 event/100 patient-year), the HEARTS-60 + 3 score showed a good predictive performance with a C-statistic (95% confidence interval) of 0.84 (0.81-0.89). CONCLUSION: The HEARTS-60 + 3 score shows a potential as a bleeding risk prediction score in MSAF or MHV patients.

RIvaroxaban in mitral stenosis (RISE MS): A pilot randomized clinical trial.

BACKGROUND: Patients with moderate-to-severe mitral stenosis (MS) have bee excluded from all major randomized controlled trials (RCTs) comparing non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin in patients with atrial fibrillation (AF). METHODS AND RESULTS: In this pilot RCT, 40 patients were randomized to rivaroxaban 20 mg daily or warfarin. No patients experienced symptomatic ischemic strokes and systemic embolic events (the primary composite study outcome) during a 12-month follow-up. No major bleeding was reported. During the follow-up, 18.2% of patients in both groups showed echocardiographic signs of increased thrombogenicity in the left atrial appendage. The rate of silent cerebral ischemia was 13.3% in the rivaroxaban group and 17.6% in the warfarin group at brain magnetic resonance imaging. CONCLUSION: Our results suggest acceptable efficacy and safety for rivaroxaban in patients with AF and moderate-to-severe MS and are encouraging for larger RCTs in this so far neglected setting (NCT03926156).

Anticoagulation in Atrial Fibrillation Associated with Mitral Stenosis.

Rheumatic valve disease is present in 0.4 % of the word population, mainly in lowincome countries. Rheumatic mitral stenosis affects more women and between 40 to 75 % of patients may have atrial fibrillation (AF), more frequently in upper-middle income countries. This rhythm disturbance is due to increased atrial pressure, chronic inflammation, fibrosis, and left atrial enlargement. There is also an increase in the prevalence of AF with age in patients with mitral stenosis. The risk of stroke is 4 % per year. Success rates for cardioversion, Cox-Maze procedure, and catheter ablation are low. Therefore, anticoagulation with vitamin K antagonist is mandatory for Evaluated Heart valves, Rheumatic or Artificial (EHRA) classification type 1. However, this anticoagulation is used by less than 80 % of those eligible and less than 30 % have the international normalized ratio in the therapeutic range. The safety and efficacy of using rivaroxaban, a direct factor Xa inhibitor anticoagulant, were demonstrated in the RIVER trial with a sample of 1005 patients with AF and bioprosthetic mitral valve. The indication for valve replacement, that is, if severe mitral stenosis or severe mitral regurgitation, was not specified. A randomized, open-label study (DAVID-MS) is underway to compare the effectiveness and safety of dabigatran and warfarin therapy for stroke prevention in patients with AF and moderate or severe mitral stenosis. Thus, the applicability of the use of direct anticoagulants in patients with AF and mitral stenosis and also in those undergoing mitral bioprostheses surgery will be the subject of further studies. The findings may explain if specific atrial changes of mitral stenosis even after the valve replacement will influence thromboembolic events with direct anticoagulants.

Bioprosthetic Valve Thrombosis and Obstruction Secondary to COVID-19.

Patients with COVID-19 may present a hypercoagulable state, with an important impact on morbidity and mortality. Because of this situation pulmonary embolism is a frequent complication during the course of infection. We present the case of a patient recently discharged, after admission with confirmed COVID-19, who developed a pulmonary embolism and thrombosis of a biological mitral valve prosthesis, producing valve obstruction and stenosis. After 15 days of anticoagulant treatment, resolution of the thrombus and normalisation of prosthetic valve function was observed. This case supports current recommendations of administering full-dose anticoagulation therapy to COVID-19 patients with biological heart valve prosthesis, even after the acute phase of infection.

A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant.

WHAT IS KNOWN AND OBJECTIVE: Direct oral anticoagulants (DOACs) are increasingly prescribed instead of warfarin for chronic anticoagulation for ease of dosing, fewer interactions, and less stringent monitoring. However, it is important to consider indications and comorbidities for which warfarin is still the preferred anticoagulant. This review aims to capture these clinical scenarios in which warfarin may still be preferred over DOACs. METHODS: We undertook a comprehensive literature search using the PubMed database. Key search terms were based on DOAC clinical trial exclusion criteria, as well as indications and conditions in which the use of DOACs for anticoagulation has suggested harm. Society guidelines and tertiary literature were used to inform expert opinion where necessary. Studies were included if they investigated the use of DOACs or warfarin in the identified indications or conditions. RESULTS AND DISCUSSION: Currently, evidence for the use of warfarin over DOACs for anticoagulation is strongest for patients with prosthetic valves, antiphospholipid syndrome, or a high risk of gastrointestinal bleeding. For several clinical situations, including mitral stenosis, obesity, altered gastrointestinal anatomy, pulmonary arterial hypertension, renal or hepatic impairment, and left ventricular thrombus, evidence is lacking but may eventually support the use of DOACs. Depending on indication and condition, appropriateness of DOAC use may vary by agent. WHAT IS NEW AND CONCLUSION: New evidence continues to support new indications and conditions in which DOACs may be appropriate to use for anticoagulation. There are key clinical scenarios, however, in which emerging literature continues to support warfarin as the preferred anticoagulant.

Cardiac Point-of-Care Ultrasound for the Diagnosis of Infective Endocarditis in a Patient with Non-Specific Rheumatologic Symptoms and Glomerulonephritis.

BACKGROUND Point-of-care ultrasound (POCUS) is performed at the bedside by a healthcare professional who is directly caring for the patient. Subacute infective endocarditis can be challenging to diagnose, as patients often present with non-specific symptoms. The modified Duke criteria include echocardiographic findings as a major criterion, but the role of POCUS has not been established. This report is of a case of infective endocarditis diagnosed using POCUS. CASE REPORT A 57-year-old man was admitted to hospital with a presumptive diagnosis of rapidly progressive glomerulonephritis secondary to vasculitis associated with a non-specific rheumatologic condition that had developed during the previous three months. Several specialist physicians had previously examined him. On hospital admission, POCUS was performed by the internal medicine physician, which showed mitral valve endocarditis resulting in a change in clinical management from steroid therapy to antibiotic therapy. Blood cultures were performed, which grew Streptococcus mutans. CONCLUSIONS To our knowledge, this is the first reported case of infective endocarditis diagnosed by an internist using POCUS in a patient admitted to hospital with an alternative diagnosis and management plan in place. This case highlights the potential role of POCUS in the acute hospital setting and supports the need for studies to compare the diagnostic performance of POCUS with transthoracic echocardiography for the detection of valvular vegetations. POCUS may be considered for patients with a possible diagnosis of infective endocarditis that cannot be excluded using the modified Duke criteria, potentially resulting in earlier diagnosis and management, with an improved clinical outcome.

Outcomes of Direct Oral Anticoagulants in Patients With Mitral Stenosis.

BACKGROUND: Patients with mitral stenosis and atrial fibrillation (AF) require anticoagulation for stroke prevention. Thus far, all studies on direct oral anticoagulants (DOACs) have excluded patients with moderate to severe mitral stenosis. OBJECTIVES: The aim of this study was to validate the efficacy of DOACs in patients with mitral stenosis. METHODS: The study population was enrolled from the Health Insurance Review and Assessment Service (HIRA) database in the Republic of Korea, and it included patients who were diagnosed with mitral stenosis and AF and either were prescribed DOACs for off-label use or received conventional treatment with warfarin. The primary efficacy endpoint was ischemic strokes or systemic embolisms, and the safety outcome was intracranial hemorrhage. RESULTS: A total of 2,230 patients (mean age 69.7 ± 10.5 years; 682 [30.6%] males) were included in the present study. Thromboembolic events occurred at a rate of 2.22%/year in the DOAC group, and 4.19%/year in the warfarin group (adjusted hazard ratio for DOAC: 0.28; 95% confidence interval: 0.18 to 0.45). Intracranial hemorrhage occurred in 0.49% of the DOAC group and 0.93% of the warfarin group (adjusted hazard ratio for DOAC: 0.53; 95% confidence interval: 0.22 to 1.26). CONCLUSIONS: In patients with AF accompanied with mitral stenosis, DOAC use is promising and hypothesis generating in preventing thromboembolism. Our results need to be replicated in a randomized trial.

Comparative efficacy of ivabradine versus beta-blockers in patients with mitral stenosis in sinus rhythm: systematic review and meta-analysis.

Background Patients with mitral valve stenosis have increased heart rate. HR reduction is known as an important treatment and therapy strategy for patients with mitral valve stenosis. Aim of the review The aim of this systematic review and meta-analysis was to compare the efficacy of ivabradine versus beta-blockers in patients with mitral stenosis in sinus rhythm. Methods Randomized controlled trials were searched in Cochrane Library, PubMed, Web of Science, CRD, Scopus, and Google Scholar with no start time limitation and ending June 2018. Risk of bias across was assessed by the Cochrane Risk of Bias Assessment tool. Fixed effects models were used to combine the results and the mean difference with a 95% confidence interval. This meta-analysis was performed using Meta Package in R software. Results Five studies entered meta-analysis. The total number of patients treated with ivabradine and beta-blockers was 178 and 178 respectively. The results showed that the mean of maximum HR and HR at rest was lower at about 5.03 units and upper 4.32 units respectively with use of ivabradine compared with the use of beta-blockers. These values were statistically significant. Conclusion It seems that the efficacy of ivabradine is good in comparison with betablockers, but it still requires more clinical trials.

Severe mitral stenosis secondary to eosinophilic granulomatosis resolving after pharmacological treatment.

We present a case of 44-year-old woman who underwent effective pharmacological treatment of severe mitral stenosis. The patient was hospitalized due to rapidly progressive dyspnea. Her medical history included asthma, perennial rhinitis, and nasal polyps. Echocardiography showed a mass of the left ventricle involving the mitral valve; cardiac MRI suggested acute endocarditis. Severe peripheral blood eosinophilia was found. Eosinophilic granulomatosis with polyangiitis was diagnosed; treatment with prednisone and cyclophosphamide was started. Despite the clinical improvement, severe mitral stenosis persisted, surgical treatment was planned. However, evaluation after 6 cycles of cyclophosphamide pulse therapy revealed a significant regression of the valvular disease.

Reversible thrombotic mitral valve stenosis after transcatheter mitral valve replacement (TMVR): Is life-long anticoagulation therapy necessary?

We describe a case of reversible thrombotic mitral valve stenosis following a valve-in-ring transcatheter mitral valve replacement. Life-long oral anticoagulation in patients who underwent transcatheter mitral valve replacement might be beneficial.

Stroke prevention strategies in patients with atrial fibrillation and heart valve abnormalities: perceptions of 'valvular' atrial fibrillation: results of the European Heart Rhythm Association Survey.

The purpose of this European Heart Rhythm Association (EHRA) Survey was to assess the perceptions of 'valvular' atrial fibrillation (AF) and management of AF patients with various heart valve abnormalities in daily clinical practice in European electrophysiology (EP) centres. Questionnaire survey was sent via the Internet to the EHRA-EP Research Network Centres. Of the 52 responding centres, 42 (80.8%) were university hospitals. Choosing the most comprehensive definition of valvular AF, a total of 49 centres (94.2%) encountered a mechanical prosthetic heart valve and significant rheumatic mitral stenosis, 35 centres (67.3%) also considered bioprosthetic valves, and 25 centres (48.1%) included any significant valvular heart disease, requiring surgical repair in the definition of valvular AF. Only three centres (5.8%) would define valvular AF as the presence of any (even mild) valvular abnormality. None of the centres would use non-vitamin K antagonist oral anticoagulants (NOACs) in AF patients with mechanical prosthetic valves, only 5 centres (9.8%) would use NOACs in patients with significant mitral stenosis, 17 centres (32.7%) would consider the use of NOACs in patients with bioprosthetic valves, and 21 centres (41.2%) would use NOACs in patients with a non-recent transcatheter valve replacement/implantation, while 13 centres (25.5%) would never consider the use of NOACs in AF patients with even mild native heart valve abnormality. Our survey showed marked heterogeneity in the definition of valvular AF and thromboprophylactic treatments, with the use of variable NOACs in patients with valvular heart disease other than prosthetic heart valves or significant mitral stenosis, indicating that this term may be misleading and should not be used.