New evidence continues to accumulate regarding a significant association between excessive inflammation and dysregulated immunity (local and systemic) and the risk of cardiovascular events in different patient cohorts. Whilst research has sought to identify novel atheroprotective therapies targeting inflammation and immunity, several marketed drugs for rheumatological conditions may serve a similar purpose. One such drug, methotrexate, has been used since 1948 for treating cancer and, more recently, for a wide range of dysimmune conditions. Over the last 30 years, epidemiological and experimental studies have shown that methotrexate is independently associated with a reduced risk of cardiovascular disease, particularly in rheumatological patients, and exerts several beneficial effects on vascular homeostasis and blood pressure control. This review article discusses the current challenges with managing cardiovascular risk and the new frontiers offered by drug discovery and drug repurposing targeting inflammation and immunity with a focus on methotrexate. Specifically, the article critically appraises the results of observational, cross-sectional and intervention studies investigating the effects of methotrexate on overall cardiovascular risk and individual risk factors. It also discusses the putative molecular mechanisms underpinning the atheroprotective effects of methotrexate and the practical advantages of using methotrexate in cardiovascular prevention, and highlights future research directions in this area.
Background: Del Nido cardioplegia (DNC) is a single-dose, high potassium, low-volume cardioplegia solution that has grown in favor recently. However, the use of DNC in the Asian population may be associated with certain challenges.
Methods: Between January 2017 and April 2022, DNC was used for myocardial protection in this single-center retrospective study. In total, 5731 patients underwent open heart surgeries, where 310 patients received DNC for single or multiple procedures. A total of 307 pair of propensity-matched patients from DNC and cold blood St. Thomas cardioplegia (STC) were compared.
Results: In total, 5085 patients with STC and 310 patients with DNC from the cohort were matched, reflecting the initial group sizes before propensity matching. About 307 patient pairs were included in the final analysis after propensity matching with the interest variables. In the STC group, the requirement for an immediate postoperative intra-aortic balloon pump (IABP) was significantly higher [18 (5.9%) in DNC versus 28 (9.1%) in STC, p = 0.021]. A 30-day mortality was comparable between the DNC and STC groups (2.9% versus 3.3%, p = 1.00). Major adverse cardiac events (MACE) (2.6% versus 3.6%, p = 0.648) showed no difference between the groups. In both single and multiple procedure subgroups, there were no statistically significant differences in 30-day mortality and MACE incidences when comparing STC and DNC.
Conclusion: The use of DNC in adults is acceptable and adaptable. Comparable clinical outcomes between STC patients and DNC were revealed by our investigation. There were no appreciable differences in 30-day mortality or MACE despite the STC group having a much higher need for immediate postoperative IABP.
Background: The use of ultrasound-based methods for imaging of subclinical atherosclerosis, including measurement of carotid plaque burden (cPB), is a promising direction for further improvement of major adverse cardiac and cerebrovascular events (MACCE) prediction.
Objectives: The aim of the study was to research the prognostic values' significance of cPB indicators with regard to the short-term progression of polyvascular subclinical atherosclerosis and the long-term onset of MACCE.
Design: Single-center prospective cohort study.
Methods: The study included patients 40-64 years of age. All patients underwent duplex scanning (DS) of the carotid and lower limb arteries. The following cPB indicators were determined: carotid plaque score (cPS), maximum carotid plaque thickness (cPTmax), and carotid total plaque area (cTPA). The combined endpoint included the following components: cardiovascular death; nonfatal myocardial infarction; nonfatal stroke or transient ischemic attack (TIA); revascularization of the coronary and/or peripheral arteries.
Results: The study included 387 patients, among whom 142 (36.7%) patients underwent repeated DS after 12-24 months. The median follow-up time was 20.0 (13.0; 36.5) months. MACCE were recorded in 33 (8.52%) of patients. cTPA and cPTmax, but not cPS, were independently associated with the progression of subclinical polyvascular atherosclerosis over a period of 13.9 months of follow-up. cTPA, but not cPTmax and cPS, was independently associated with the development of MACCE over a period of 20.0 months of follow-up. Only a cTPA > 42.0 mm2 proved to be an independent predictor of both the progression of subclinical polyvascular atherosclerosis and MACCE.
Conclusion: In patients from 40 to 64 years of age with various cardiovascular risks, among the indicators of the cPB, only an increase in cTPA > 42.0 mm2 was shown to be independently associated with an increase in the relative risk (RR) of progression of subclinical polyvascular atherosclerosis by 2.38 (1.08-5.25) times, as well as with the development of MACCE by 3.10 (1.54-6.26) times.
Background: Since their emergence, drug-coated balloons (DCBs) have been used widely to treat in-stent lesions with coronary artery disease (CAD). However, despite their superior efficacy to balloon angioplasty, how DCBs affect neointimal characteristics is poorly understood.
Objectives: We aimed to assess the neointimal characteristic changes following DCB treatment.
Methods: Using optical frequency domain imaging (OFDI), we serially observed the in-stent lesion site just after and 1 year after DCB angioplasty in 12 lesions of 11 patients with repeated revascularization. Neoatherosclerosis was defined as lipid-laden neointima with or without calcification in the stented lesion. Progression or regression of neoatherosclerosis, newly formed neointimal calcification, newly formed uncovered strut and newly formed evagination were assessed. Tiny tissue protrusion was also recorded as mushroom-like protrusion.
Results: Underlying stents were first-generation (n = 5) or newer (n = 7) drug-eluting stents (DESs) with implantation durations ranging from 1 to 15 years (median 8 years). Surprisingly, two-thirds of the lesions (67%, 8 of 12) showed progression of neoatherosclerosis, while a quarter of lesions (25%, 3 of 12) showed regression of neoatherosclerosis. The maximal lipid arc increased from 122° to 174°. Newly formed neointimal calcification was observed in 2 of 12 lesions (16%). Newly formed uncovered struts (33%; 4 of 12) and newly formed evaginations (33%; 4 of 12) were not rare. Mushroom-like protrusion was found in a quarter of lesions (25%; 3 of 12).
Conclusion: Our study demonstrated that a considerable number of lesions showed varied neointimal characteristic changes in a small number of patients. Further studies in a larger population are needed to understand the clinical impact of these findings.
Aims: Oral anticoagulation with direct oral anticoagulants (DOAC) could provide an alternative to vitamin K antagonists (VKA) for patients with atrial fibrillation (AF) undergoing bioprosthetic heart valve replacement or valve repair.
Methods and results: The aim of this meta-analysis was to review the safety and efficacy of DOAC in patients with surgical implanted bioprosthetic heart valves or valve repairs and AF including data from six clinical trials with a total of 1,857 patients. The efficacy and safety data of DOAC and VKA were pooled to perform random-effects meta-analyses using the Mantel-Haenszel method with pooled risk ratios (RR) and 95% confidence interval (CI). A trial sequential analysis (TSA) was performed to assess statistical robustness. Death caused by cardiovascular cause or thromboembolic events were comparable (RR 0.67, 95% CI: 0.42-1.08; p = 0.10) as DOAC significantly reduced the risk for major bleeding (RR 0.55, 95% CI: 0.35-0.88; p = 0.01) and thromboembolic stroke or systemic embolism rates (RR 0.54, 95% CI: 0.32-0.90; p = 0.02). Rates for intracranial bleeding and hemorrhagic stroke (RR 0.27, 95% CI: 0.07-0.99; p = 0.05) show a trend toward fewer events in the DOAC group. Outcomes for major or minor bleeding events and all-cause mortality were comparable for DOAC and VKA.
Conclusion: Cumulative data analysis reveals that DOAC may provide an effective and safe alternative to VKA in patients with AF after surgically implanted bioprosthetic heart valves or repair with AF. Within a relatively heterogeneous study population, this meta-analysis shows a risk reduction of major bleedings and thromboembolic stroke or systemic embolisms for DOAC.
Purpose: Baroreflex activation therapy has favorable effects in heart failure patients. We report the results of a single-center study of baroreflex activation therapy in heart failure with reduced ejection fraction including cardiopulmonary exercise testing for the first time to show the effect on exercise capacity.
Methods: A total of 17 patients were treated with baroreflex activation therapy. Eligibility criteria were the New York Heart Association class ⩾III and ejection fraction ⩽35% on guideline-directed medical and device therapy. The New York Heart Association class, quality of life, and 6-min hall walk distance were assessed in all patients. Twelve patients underwent cardiopulmonary exercise testing before and 8.9 ± 6.4 months after initiation of baroreflex activation therapy.
Results: The New York Heart Association class and 6-min hall walk distance improved after baroreflex activation therapy, while quality of life remained stable. Weight-adapted peak oxygen uptake increased significantly from 10.1 (8.2-12.9) ml/min/kg to 12.1 (10.4-14.6) ml/min/kg (p = 0.041). Maximal heart rate was stable. Maximal oxygen pulse increased from 9.7 (5.5-11.3) to 9.9 (7.1-12.1) ml/heartbeat (p = 0.047) in 10 patients with low maximal oxygen pulse at baseline (<16.5 ml/heartbeat). There was no significant change in maximal oxygen pulse in the whole cohort. Ventilatory efficiency remained stable.
Conclusion: Weight-adapted peak oxygen uptake improved after baroreflex activation therapy, pointing to an enhanced exercise capacity. Ventilatory efficiency and heart rate did not change, while oxygen pulse increased in patients with low oxygen pulse at baseline, indicating an improvement in circulatory efficiency, that is, a beneficial effect on stroke volume and peripheral oxygen extraction.
Background: Peripheral artery disease affects over 236 million people globally and the classic symptom is intermittent claudication (IC) which is associated with reduction in physical activity. The evidence that supervised exercise programmes (SEPs) improve pain-free and maximal walking distance is irrefutable. However, adherence rates are low with exercise-related pain cited as a contributing factor. National and international guidelines recommend exercising at a moderate to maximal level of claudication pain to improve walking ability; however, exercising pain-free or at mild claudication pain has been shown to achieve this outcome. There is limited evidence that compares the relative effects of exercise prescribed at different levels of claudication pain.
Objective: The objective of this study is to directly compare the effects of exercise prescribed at three different levels of claudication pain on walking performance.
Design: This study will be a single-centre randomised controlled trial.
Methods: Based on an a priori power calculation, 51 patients with IC will be allocated to 24 weeks of twice-weekly pain-free (PF), moderate pain (MOD-P) or maximal pain (MAX-P) exercise. The PF group will cease exercise at the onset of claudication (1 on the 0-4 IC rating scale), the MOD-P group will stop once moderate pain is reached (2 on the rating scale) and the MAX-P group will stop once maximal pain is reached (4 on the rating scale).
Analysis: Outcome measures will be assessed at baseline, 12 and 24 weeks adopting an analysis of covariance (ANCOVA) to compare MWD across three time points. The primary outcome for the trial will be change in maximal treadmill walking distance at 12 and 24 weeks.
Registration: Trial registration number: NCT04370327.
Intracardiac thrombus in the left atrium and atrial appendage (LA/LAA) and left ventricle (LV) increases the risk of systemic thromboembolism and causes potentially devastating diseases such as ischemic stroke and acute ischemia in abdominal organs and lower extremities. Detecting the presence and monitoring the resolution of left heart intracardiac thrombus are of vital importance for stratifying patients and guiding treatment decisions. Currently, echocardiography is the most frequently used method for the above clinical needs, followed by computed tomography. An increasing number of studies have been performed to investigate the value of cardiac magnetic resonance (CMR) as an alternative imaging modality given its several unique strengths. This article provides an overview of the clinical relevance of the LA/LAA and LV thrombus as well as the diagnostic performance of the current imaging modalities and emerging CMR techniques.
Background: Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to some routine prescriptions and changed some patient health behaviours.
Aim: This study, therefore, retrospectively investigated prescription reimbursement of cardiovascular (CVD) medicines as a proxy measure for patient adherence and access to medicines during the pandemic.
Methods: A cohort study of all primary care patients in England prescribed CVD medicines. The exposure was to the global pandemic. Prescriptions were compared before and after the pandemic's onset. Statistical variation was the outcome of interest.
Results: Descriptive statistics show changes to monthly prescriptions, with wide confidence intervals indicating varying underlying practice. Analysis of variance reveals statistically significant differences for bendroflumethiazide, potassium-sparing diuretics, nicorandil, ezetimibe, ivabradine, ranolazine, colesevelam and midodrine. After the pandemic began (March-October 2020), negative parameters are observed for ACE inhibitors, beta-blockers, calcium channel blockers, statins, antiplatelet, antithrombotics, ARBs, loop diuretics, doxazosin, bendroflumethiazide, nitrates and indapamide, indicating decelerating monthly prescription items (statistically significant declines of calcium channel blockers, antithrombotic, adrenoreceptor blockers and diuretics) of CVD medicines within the general population. Many data points are not statistically significant, but fluctuations remain clinically important for the large population of patients taking these medications.
Conclusion: A concerning decline in uptake of CVD therapies for chronic heart disease was observed. Accessible screening and treatment alongside financial relief on prescription levies are needed. A video abstract is (4 min 51 s) available: https://bit.ly/39gvEHi.
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