Therapeutic Advances in Cardiovascular Disease最新文献

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.

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.

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.

Peripheral artery disease (PAD) is a disease of atherosclerosis in the lower extremities. PAD carries a massive burden worldwide, while diagnosis and treatment options are often lacking. One of the key points of research in recent years is the involvement of microRNAs (miRNAs), which are short 20-25 nucleotide single-stranded RNAs that can act as negative regulators of post-transcriptional gene expression. Many of these miRNAs have been discovered to be misregulated in PAD patients, suggesting a potential utility as biomarkers for PAD diagnosis. miRNAs have also been shown to play an important role in many different pathophysiological aspects involved in the initiation and progression of the disease including angiogenesis, hypoxia, inflammation, as well as other cellular functions like cell proliferation and migration. The research on miRNAs in PAD has the potential to lead to a whole new class of diagnostic tools and treatments.

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.

Introduction: Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in COVID-19 disease is associated with widespread inflammation and a prothrombotic state, resulting in frequent venous thromboembolic (VTE) events. It is currently unknown whether anticoagulation is protective for VTE events. Therefore, we conducted a systematic review to identify predictors of VTE in COVID-19.

Methods: We searched PubMed, EMBASE, Google Scholar, and Ovid databases for relevant observational studies of VTE in COVID-19 disease. The effect size for predictors of VTE was calculated using a random-effects model and presented as forest plots. Heterogeneity among studies was expressed as Q statistics and I². Bias was assessed using the Newcastle Ottawa Scale for all identified observational studies. Publication bias was assessed with funnel plot analysis.

Results: We identified 28 studies involving 6053 patients with suspected or confirmed COVID-19. The overall pooled prevalence of VTE events was 20.7%. Male sex was associated with a higher risk of VTE events, whereas prior history of VTE, smoking, and cancer were not. VTE events were significantly higher in severely ill patients, mechanically ventilated patients, those requiring intensive care admission, and those with a low PaO₂/FiO₂ ratio (P/F ratio). Chronic comorbidities, including cardiovascular disease, heart failure, renal disease, and pulmonary disease, did not increase the risk of VTE events. Patients with VTE had higher leukocyte counts and higher levels of D-dimer, C-reactive protein, and procalcitonin. The occurrence of VTE was associated with increased length of stay but did not impact mortality. Therapeutic and prophylactic doses of anticoagulation were not protective against VTE.

Conclusion: VTE in COVID-19 is associated with male gender and severe disease but not with traditional risk factors for VTE. The occurrence of VTE does not appear to be mitigated by either prophylactic or therapeutic anticoagulation. The occurrence of VTE in this population is associated with an increased length of stay but does not appear to impact mortality.

Introduction: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms.

Methods: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed.

Results: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: -70.86 to -40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: -37.19 to -13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure (p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) (n = 5), phrenic nerve stimulation (n = 3) and ventricular ectopy (n = 1).

Conclusion: In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration.