Human microRNAs (miRs) have been implicated in human diseases presumably through the downregulation and silencing of targeted genes via post-translational modifications. However, their role in the ...early stage of coronary atherosclerosis is not known. The aim of this study was to test the hypothesis that patients with early atherosclerosis and coronary endothelial dysfunction (CED) have alterations in transcoronary miR gradients. Patients underwent coronary angiography and endothelial function testing in the cardiac catheterization laboratory. Patients were divided into abnormal (n = 26) and normal (n = 22) microvascular coronary endothelial function based on intracoronary response to infused acetylcholine measured as a percent change in coronary blood flow (CBF) and arterial diameter. Blood samples were obtained simultaneously from the aorta and coronary sinus at the time of catheterization for RNA isolation, and miR subsequently assessed. Baseline characteristics were similar in both groups. Patients with microvascular CED displayed transcoronary gradients significantly elevated in miR-92a and miR-133 normalized to C-elegans-39 miR. Percent change in CBF and the transcoronary gradient of miR-133 displayed a significant inverse correlation (r2 = 0.11, p = 0.03). Thus, we present novel data whereupon selected miRs demonstrate elevated transcoronary gradients in patients with microvascular CED. The current findings support further studies on the mechanistic role of miRs in coronary atherosclerosis and in humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During the past three decades, percutaneous coronary intervention has become one of the cardinal treatment strategies for stenotic coronary artery disease. Technical advances, including the ...introduction of new devices such as stents, have expanded the interventional capabilities of balloon angioplasty. At the same time, there has been a decline in the rate of major adverse cardiac events, including Q-wave acute myocardial infarction, emergency coronary artery bypass grafting, and cardiac death. Despite these advances, the incidence of post-procedural cardiac marker elevation has not substantially decreased since the first serial assessment 20 years ago. As of now, these post-procedural cardiac marker elevations are considered to represent peri-procedural myocardial injury (PMI) with worse long-term outcome potential. Recent progress has been made for the identification of two main PMI patterns, one near the intervention site (proximal type, PMI type I) and one in the distal perfusion territory of the treated coronary artery (distal type, PMI type II) as well as for preventive strategies. Integrating these new developments into the wealth of clinical information on this topic, this review aims at giving a current perspective on the entity of PMI.
Heart failure is a dreaded complication of trastuzumab therapy in women with breast cancer overexpressing the human epidermal growth factor receptor (HER)-2. Experimental studies have pointed out ...that the HER-2 signaling pathway is important in the adaptation to high afterload conditions and its inactivation leads to cardiac decompensation. Herein, we report on 2 patients with breast cancer who were receiving trastuzumab monotherapy and required hospital admission for new-onset heart failure. This occurred at a time of unprecedented blood pressure elevations, in one case due to cessation of antihypertensive medications and in the other case due to a scleroderma crisis. Although trastuzumab may not have been the precipitating factor for blood pressure dyscontrol in these patients, severe, uncontrolled hypertension may have been the precipitating factor for trastuzumab-related acute heart failure. These 2 cases add to previous reports recognizing systemic hypertension as a risk factor for the development of trastuzumab cardiotoxicity and translate experimental observations of the significance of the HER-2 signaling pathway to the bedside. Pending further confirmation, the present observations may raise awareness of the need for appropriate monitoring and control of systemic hypertension in patients receiving trastuzumab, or potentially any other HER-2-targeted therapy.
Background Treatment for breast cancer (BC) frequently involves radiotherapy. Guidelines recommend screening for cardiac adverse events starting 10 years after radiotherapy. The rationale for this ...interval is unclear. Methods and Results We aimed to study cardiovascular event rates in the first decade following curative radiotherapy for BC. We compared mortality and cardiovascular event rates with an age- and risk factor-matched control population. We included 1095 patients with BC (mean age 56±12 years). Two hundred and eighteen (19.9%) women died. Cancer and cardiovascular mortality caused 107 (49.1%) and 22 (10.1%) deaths, respectively. A total of 904 cases were matched to female FLEMENGHO (Flemish Study on Environment, Genes and Health Outcomes) participants. Coronary artery disease incidence was similar (risk ratio RR, 0.75 95% CI, 0.48-1.18), yet heart failure (RR, 1.97 95% CI, 1.19-3.25) and atrial fibrillation/flutter (RR, 1.82 95% CI, 1.07-3.08) occurred more often in patients with BC. Age (hazard ratio HR, 1.033 95% CI, 1.006-1.061,
=0.016), tumor grade (HR, 1.739 95% CI, 1.166-2.591,
=0.007), and neoadjuvant treatment setting (HR, 2.782 95% CI, 1.304-5.936,
=0.008) were risk factors for mortality. Risk factors for major adverse cardiac events were age (HR, 1.053 95% CI, 1.013-1.093;
=0.008), mean heart dose (HR, 1.093 95% CI, 1.025-1.167;
=0.007), history of cardiovascular disease (HR, 2.386 95% CI, 1.096-6.197;
=0.029) and Mayo Clinic Cardiotoxicity Risk Score (HR, 2.664 95% CI, 1.625-4.367;
<0.001). Conclusions Ten-year mortality following curative treatment for unilateral BC was mainly cancer related, but heart failure and atrial fibrillation/flutter were already common in the first decade following irradiation. Mean heart dose, pre-existing cardiovascular diseases, and Mayo Clinic Cardiotoxicity Risk Score were risk factors for cardiac adverse events. These results suggest a need for early dedicated cardio-oncological follow-up after radiotherapy.
Background Temporal declines in cardiac stress tests results, coronary revascularization, and cardiovascular mortality have suggested a decline in the population burden of coronary disease until the ...2000s. However, recent data indicate these favorable trends could be ending. We aimed to assess the evolution of the population burden of coronary disease in the community by examining trends in angiography and revascularization. Methods and Results We analyzed age- and sex-adjusted trends from all coronary angiographic diagnostic procedures and revascularizations performed in Olmsted County, MN from 2000 to 2018. A total of 12 981 invasive angiograms were performed among 9049 individuals (64% men; 55% aged ≥65 years). Adjusted angiography rates decreased by 30% (95% CI, 25%-34%) between 2000 and 2009 and leveled off thereafter. Including computed tomography, angiography uncovered an increase in angiography use in recent years (risk ratio=1.15 95% CI, 1.07-1.23 for 2018 versus 2014) and a decline in the prevalence of anatomic CAD from 2000 to 2018. CAD severity declined substantially from 2000 to 2009, followed by a plateau. Among 6570 revascularizations (72% men; 57% aged ≥65 years), 77% were percutaneous coronary interventions and 23% coronary artery bypass graft surgeries. The adjusted revascularization rates declined by 34% (95% CI, 27%-39%) from 2000 to 2009, followed by a plateau (risk ratio=1.10 95% CI, 1.00-1.22). Conclusions Between 2000 and 2018 in the community, coronary angiography use declined initially, leveled off, and then increased. Trends in CAD severity and revascularization use decreased then plateaued. The most recent trends are concerning as they suggest the burden of coronary disease is no longer declining. This warrants reinvigorated primary prevention and population surveillance.
Background: Myocardial bridging (MB) results in compression of the coronary artery lumen in systole, extending into diastole with resultant hemodynamic alternation as reflected by fractional flow ...reserve (FFR). MB has also been associated with coronary endothelial dysfunction. The objective of this study was to investigate relationship between FFR with dobutamine challenge and coronary microvascular endothelial dysfunction in symptomatic MB. Methods and Results: Seventeen consecutive patients who had cardiac catheterization assessment of MB were enrolled. The patients were divided into 2 groups according to normal (% increase in coronary blood flow %CBF ≥50%, n=7) or impaired (%CBF <50%, n=10) coronary microvascular endothelial function assessed on vasoreactivity in the coronary artery with intracoronary infusion of acetylcholine (Ach). Myocardial ischemia was then assessed using FFR at rest and during i.v. dobutamine infusion challenge across the MB with intracoronary pressure wires. FFR was significantly decreased at peak dobutamine infusion compared to at rest in the impaired group (0.85±0.06 vs. 0.91±0.05, P=0.001), but not in the normal group (0.93±0.05 vs. 0.91±0.07, P=0.618). Both FFR at rest and at peak dobutamine infusion had a positive correlation with %CBF by Ach in the impaired group (r2=0.46, P=0.030; r2=0.52, P=0.018, respectively). Conclusions: Microvascular endothelial dysfunction was associated with decreased FFR at peak dobutamine stress in patients with symptomatic MB. (Circ J 2014; 78: 685–692)
Carfilzomib is a selective proteasome inhibitor approved for the treatment of relapsed and/or refractory multiple myeloma (RRMM). It has significantly improved outcomes, including overall survival ...(OS), and shown superiority vs standard treatment with lenalidomide plus dexamethasone and bortezomib plus dexamethasone. The incidence rate of cardiovascular (CV) events with carfilzomib treatment has varied across trials. This analysis evaluated phase 1-3 trials with >2000 RRMM patients exposed to carfilzomib to describe the incidence of CV adverse events (AEs). In addition, the individual CV safety data of >1000 patients enrolled in the carfilzomib arm of phase 3 studies were compared with the control arms to assess the benefit-risk profile of carfilzomib. Pooling data across carfilzomib trials, the CV AEs (grade ≥3) noted included hypertension (5.9%), dyspnea (4.5%), and cardiac failure (4.4%). Although patients receiving carfilzomib had a numeric increase in the rates of any-grade and grade ≥3 cardiac failure, dyspnea, and hypertension, the frequency of discontinuation or death due to these cardiac events was low and comparable between the carfilzomib and control arms. Serial echocardiography in a blinded cardiac substudy showed no objective evidence of cardiac dysfunction in the carfilzomib and control arms. Moreover, carfilzomib had no significant effect on cardiac repolarization. Our results, including the OS benefit, showed that the benefit of carfilzomib treatment in terms of reducing progression or death outweighed the risk for developing cardiac failure or hypertension in most patients. Appropriate carfilzomib administration and risk factor management are recommended for elderly patients and patients with underlying risk factors.
•Despite increased incidence of CV events, relative risk of CV AEs with carfilzomib is low and manageable; risk of fatal AEs is not elevated.•Carfilzomib-based regimens have a favorable benefit-risk profile in RRMM; monitoring/management of CV risk is recommended.
Display omitted
Despite advances in therapy, coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide. Over the past years, the utilization of revascularization procedures has ...been refined, and in the best interest of the patient and to reduce the healthcare burden of CAD, it is paramount that patients are appropriately selected for therapies aiming at improving their symptoms and prognosis. Fractional flow reserve (FFR) is the current invasive standard test to identify hemodynamically significant coronary artery stenoses with resultant implications for revascularization and clinical outcomes. In this review, we discuss the current evidence behind the use of FFR as well as new trends in the application of this technique to help guide clinicians in making the best management decisions for patients with CAD.
Objectives:
This study sought to systematically analyze the available clinical evidence on TAVR therapy in cancer patients with symptomatic severe AS.
Background:
Aortic stenosis is the most common ...valvular heart disease in the world. TAVR has expanded the treatment options for this lethal disease process. The safety and efficacy of TAVR in cancer patients has not yet been reliably established. We thus conducted the largest known multi-center meta-analysis on TAVR and cancer status.
Methods:
We performed a literature search using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials from January 2015 to 2020. Studies that compared the use of TAVR in patients with severe symptomatic aortic stenosis and cancer against patients without cancer were included. Meta-regression was also conducted to determine if common clinical factors modified the possible association between cancer status and TAVR mortality.
Results:
Five studies with 11,129 patients in the cancer group and 41,706 patients in the control group met inclusion criteria. The short-term mortality in the cancer group was 2.4% compared with 3.3% in the control group (odds ratio: 0.72, 95% confidence interval: 0.63–0.82;
p
< 0.0001). The frequency of stroke was 2.4% compared with 2.7% (odds ratio of 0.87, 95% confidence interval: 0.76–0.99;
p
< 0.04). The frequency of AKI was 14.2% in cancer patients vs. 16.4% (odds ratio of 0.81, 95% confidence interval: 0.76–0.85;
p
< 0.04). The rates of bleeding and need for new pacemaker implantation were not significantly different. Meta-regression demonstrated there was no significant association modifying.
Conclusions:
On the basis of the results of this meta-analysis TAVR may be a safe and effective therapeutic option for patients with cancer and symptomatic severe aortic stenosis. Larger, longer, and randomized trials are required to adequately test this above hypothesis.
PDF
