Coronary Artery Vasospasm Induced by 5-fluorouracil: Proposed Mechanisms, Existing Management Options and Future Directions

Cardiovascular disease and cancer are leading contributors to the global disease burden. As a result of cancer therapy-related cardiotoxicities, cardiovascular disease results in significant morbidity and mortality in cancer survivors and patients with active cancer. There is an unmet need for management of cardio-oncology conditions, which is predicted to reach epidemic proportions, and better understanding of their pathophysiology and treatment is urgently required. The proposed mechanisms underlying cardiotoxicity induced by 5-fluorouracil (5-FU) are vascular endothelial damage followed by thrombus formation, ischaemia secondary to coronary artery vasospasm, direct toxicity on myocardium and thrombogenicity. In patients with angina and electrocardiographic evidence of myocardial ischaemia due to chemotherapy-related coronary artery vasospasm, termination of chemotherapy and administration of calcium channel blockers or nitrates can improve ischaemic symptoms. However, coronary artery vasospasm can reoccur with 5-FU re-administration with limited effectiveness of vasodilator prophylaxis observed. While pre-existing coronary artery disease may increase the ischaemic potential of 5-FU, cardiovascular risk factors do not appear to completely predict the development of cardiac complications. Pharmacogenomic studies and genetic profiling may help predict the occurrence and streamline the treatment of 5-FU-induced coronary artery vasospasm. Echocardiographic measures such as the Tei index may help detect subclinical 5-FU cardiotoxicity. Further research is required to explore the cardioprotective effect of agents such as coenzyme complex, GLP-1 analogues and degradation inhibitors on 5-FU-induced coronary artery vasospasm

DOACs for stroke prevention in patients with AF and cancer

Stroke prophylaxis in atrial fibrillation is an important consideration in patients with cancer. However, there is little consensus on the choice of anticoagulation, due to the numerous difficulties associated with active cancer. Direct oral anticoagulants (DOACs) have been shown to be a promising option. Here, we conduct a simple cross-sectional analysis of 29 cancer patients receiving DOACs for stroke prophylaxis in atrial fibrillation at a tertiary-care institution in London. Our study demonstrates an encouraging efficacy and safety profile of DOACs used in this setting. We conclude by suggesting that, while DOACs may be useful, anticoagulation in cancer patients should continue to be individualised

Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study

Background: People of South Asian and African Caribbean ethnicities living in UK have a high risk of cardiometabolic disease. Limited data exist regarding detailed cardiometabolic phenotyping in this population. Methods enabling this are widely available, but the practical aspects of undertaking such studies in large and diverse samples are seldom reported.Methods: The Southall and Brent Revisited (SABRE) study is the UK's largest tri-ethnic longitudinal cohort. Over 1,400 surviving participants (58–85 years) attended the 2nd study visit (2008–2011); during which, comprehensive cardiovascular phenotyping, including 3D-echocardiography [3D-speckle-tracking (3D-STE)], computed tomography, coronary artery calcium scoring, pulse wave velocity, central blood pressure, carotid artery ultrasound, and retinal imaging, were performed. We describe the methods used with the aim of providing a guide to their feasibility and reproducibility in a large tri-ethnic population-based study of older people.Results: Conventional echocardiography and all vascular measurements showed high feasibility (>90% analyzable of clinic attendees), but 3D-echocardiography (3DE) and 3D-STE were less feasible (71% 3DE acquisition feasibility and 38% 3D-STE feasibility of clinic attendees). 3D-STE feasibility differed by ethnicity, being lowest in South Asian participants and highest in African Caribbean participants (p < 0.0001). Similar trends were observed in men (P < 0.0001) and women (P = 0.005); however, in South Asians, there were more women with unreadable 3D-images compared to men (67 vs. 58%). Intra- and inter-observer variabilities were excellent for most of conventional and advanced echocardiographic measures. The test-retest reproducibility was good-excellent and fair-good for conventional and advanced echocardiographic measures, respectively, but lower than when re-reading the same images. All vascular measures demonstrated excellent or fair-good reproducibility.Conclusions: We describe the feasibility and reproducibility of detailed cardiovascular phenotyping in an ethnically diverse population. The data collected will lead to a better understanding of why people of South Asian and African Caribbean ancestry are at elevated risk of cardiometabolic diseases

Chest Pain in the Cancer Patient

Chest pain is one of the most common presenting symptoms in patients seeking care from a physician. Risk assessment tools and scores have facilitated prompt diagnosis and optimal management in these patients; however, it is unclear as to whether a standardised approach can adequately triage chest pain in cancer patients and survivors. This is of concern because cancer patients are often at an increased risk of cardiovascular mortality and morbidity given the shared risk factors between cancer and cardiovascular disease, compounded by the fact that certain anti-cancer therapies are associated with an increased risk of cardiovascular events that can persist for weeks and even years after treatment. This article describes the underlying mechanisms of the most common causes of chest pain in cancer patients with an emphasis on how their management may differ to that of non-cancer patients with chest pain. It will also highlight the role of the cardio-oncology team, who can aid in identifying cancer therapy-related cardiovascular side-effects and provide optimal multidisciplinary care for these patients

Life Course Socioeconomic Position: associations with cardiac structure and function at age 60-64 years in the 1946 British Birth Cohort

Although it is recognized that risks of cardiovascular diseases associated with heart failure develop over the life course, no studies have reported whether life course socioeconomic inequalities exist for heart failure risk. The Medical Research Council’s National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and measures of cardiac structure [left ventricular (LV) mass index and relative wall thickness (RWT)] and function [systolic: ejection fraction (EF) and midwall fractional shortening (mFS); diastolic: left atrial (LA) volume, E/A ratio and E/e’ ratio)]. Different life course models were compared with a saturated model to ascertain the nature of the relationship between socioeconomic position across the life course and each cardiac marker. Findings showed that models where socioeconomic position accumulated over multiple time points in life provided the best fit for 3 of the 7 cardiac markers: childhood and early adulthood periods for the E/A ratio and E/e’ ratio, and all three life periods for LV mass index. These associations were attenuated by adjustment for adiposity, but were little affected by adjustment for other established or novel cardio-metabolic risk factors. There was no evidence of a relationship between socioeconomic position at any time point and RWT, EF, mFS or LA volume index. In conclusion, socioeconomic position across multiple points of the lifecourse, particularly earlier in life, is an important determinant of some measures of LV structure and function. BMI may be an important mediator of these associations

THE SPLICEOSOMAL PROTEIN SnRNP F BINDS TO BOTH U3 AND U14 CLASS OF snoRNA IN Giardia lamblia

Small nuclear Ribonucleo Protein F (snRNP F) is a spliceosomal protein that binds with U1, U2, U4/U6 and U5 small nuclear RNA (snRNA) to form spliceosomal complexes responsible for pre mRNA processing. This study reports the unusual interaction of giardial snRNP F with small nucleolar RNAs (snoRNA) that are responsible for pre rRNA processing. Electrophoretic Mobility Shift Assay was used to demonstrate the interaction of this protein with U3 and U14 class snoRNA of the early branching eukaryote Giardia lamblia. It was also evident from our study that snRNP F in Giardia is evolutionary distinct from its other eukaryotic orthologues

Rate of telomere shortening and cardiovascular damage: a longitudinal study in the 1946 British Birth Cohort.

AIM: Cross-sectional studies reported associations between short leucocyte telomere length (LTL) and measures of vascular and cardiac damage. However, the contribution of LTL dynamics to the age-related process of cardiovascular (CV) remodelling remains unknown. In this study, we explored whether the rate of LTL shortening can predict CV phenotypes over 10-year follow-up and the influence of established CV risk factors on this relationship. METHODS AND RESULTS: All the participants from the MRC National Survey of Health and Development (NSHD) with measures of LTL and traditional CV risk factors at 53 and 60-64 years and common carotid intima-media thickness (cIMT), cardiac mass and left ventricular function at 60-64 years were included. LTL was measured by real-time polymerase chain reaction and available at both time points in 1033 individuals. While LTL at 53 years was not linked with any CV phenotype at 60-64 years, a negative association was found between LTL and cIMT at 60-64 years (β = -0.017, P = 0.015). However, the strongest association was found between rate of telomere shortening between 53 and 60-64 years and values of cIMT at 60-64 years (β = -0.020, P = 0.006). This association was not affected by adjustment for traditional CV risk factors. Cardiac measurements were not associated with cross-sectional or longitudinal measures of LTL. CONCLUSION: These findings suggest that the rate of progression of cellular ageing in late midlife (reflected by the rate of LTL attrition) relates to vascular damage, independently from contribution of CV risk factor exposure

Heart Failure Readmission in Patients With ST-Segment Elevation Myocardial Infarction and Active Cancer

BackgroundAlthough numerous studies have examined readmission with heart failure (HF) after acute myocardial infarction (AMI), limited data are available on HF readmission in cancer patients post-AMI. ObjectivesThis study aimed to assess the rates and factors associated with HF readmission in cancer patients presenting with ST-segment elevation myocardial infarction (STEMI). MethodsA nationally linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project registry and the UK national Hospital Episode Statistics Admitted Patient Care registry. Multivariable Fine-Gray competing risk models were used to evaluate HF readmission at 30 days and 1 year. ResultsA total of 326,551 STEMI indexed admissions were included, with 7,090 (2.2%) patients having active cancer. The cancer group was less likely to be admitted under the care of a cardiologist (74.5% vs 81.9%) and had lower rates of invasive coronary angiography (62.2% vs 72.7%; P < 0.001) and percutaneous coronary intervention (58.4% vs. 69.5%). There was a significant prescription gap in the administration of post-AMI medications upon discharge such as an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (49.5% vs 71.1%) and beta-blockers (58.4% vs 68.0%) in cancer patients. The cancer group had a higher rate of HF readmission at 30 days (3.2% vs 2.3%) and 1 year (9.4% vs 7.3%). However, after adjustment, cancer was not independently associated with HF readmission at 30 days (subdistribution HR: 1.05; 95% CI: 0.86-1.28) or 1 year (subdistribution HR: 1.03; 95% CI: 0.92-1.16). The opportunity-based quality indicator was associated with higher rates of HF readmission independent of cancer diagnosis. ConclusionsCancer patients receive care that differs in important ways from patients without cancer. Greater implementation of evidence-based care may reduce HF readmissions, including in cancer patients