Cardiovascular Risk in Cancer Patients Treated with Immune Checkpoint Inhibitors: Challenges and Future Directions.

Cardiovascular disease is the leading cause of non-cancer related mortality and morbidity among people living with or cured from cancer. Immune checkpoint inhibitors (ICIs) are systemic anti-cancer therapies that have revolutionised the treatment of numerous cancers, even achieving durable long-term responses among patients with metastatic disease. However, the pro-inflammatory effects of ICIs have been postulated to increase the risk of atherosclerotic cardiovascular disease (ASCVD) in cancer survivorship. Standard modifiable cardiovascular risk factors can further contribute to ASCVD risk during cancer survivorship but are not routinely screened and are often untreated in patients with cancer. With the expanding use of ICIs leading to improved cancer survivorship, cardiovascular risk identification and prevention will be paramount in the care of patients with cancer. This review highlights the practical challenges associated with ASCVD prevention among the growing number of patients treated with ICIs for cancer, including balancing competing mortality risks from cancer and ASCVD, the lack of ICI-specific cardiovascular risk stratification tools, potential interactions between cardiovascular and oncological therapies, and barriers to implementation of cardiovascular screening and prevention within existing healthcare systems.

Atrial fibrillation in cancer survivors - a systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac complication during cancer treatment. It is unclear if cancer survivors have increased AF risk when compared to the population. AF screening is now recommended in patients ≥65 years, however there are no specific recommendations in the oncology population. We sought to compare the AF detection rate of cancer survivors compared to the general population. METHODS: We searched the Pubmed, Embase and Web of Science databases using search terms related to AF and cancer mapped to subject headings. We included English language studies, limited to adults > 18 years who were > 12 months post completion of cancer treatment. Using a random-effects model we calculated the overall AF detection rate. Meta-regression analysis was performed to assess for potential causes for study heterogeneity. RESULTS: Sixteen studies were included in the study. The combined AF detection rate amongst all the studies was 4.7% (95% C.I 4.0-5.4%), which equated to a combined annualised AF rate of 0.7% (95% C.I 0.1-0.98%). There was significant heterogeneity between studies (I2 = 99.8%, p < 0.001). In the breast cancer cohort (n = 6 studies), the combined annualised AF rate was 0.9% (95% C.I 0.1-2.3%), with significant heterogeneity (I2 = 99.9%, p < 0.001). CONCLUSION: Whilst the results should be interpreted with caution due to study heterogeneity, AF rates in patients with cancer survival >12 months were not significantly increased compared to the general population. STUDY REGISTRATION: Open Science Framework - DOI: https://doi.org/10.17605/OSF.IO/APSYG .

Pyopneumopericarditis from a gastropericardial fistula: a case report.

BACKGROUND: Pyopneumopericarditis is a very rare diagnosis that requires prompt recognition and urgent treatment. It denotes the presence of pus and air in the pericardium with associated inflammation of the fibrous pericardial sac. CASE SUMMARY: A 49-year-old gentleman was admitted with pyopneumoperciarditis on a background of a previous uncomplicated Roux-en-Y gastric bypass surgery performed 7 years prior. He underwent emergency surgery for an omental patch repair of an ulcer perforation involving the diaphragm and pericardium. His inpatient stay was complicated by persistent seropurulent output from the pericardial drain, loculated pleural effusion, and deconditioning. DISCUSSION: Management is extrapolated from the literature regarding purulent pericarditis. This condition albeit rare, requires swift recognition as without treatment mortality approaches 100%. Colchicine is an important adjunctive therapy postoperatively to prevent constrictive physiology.

Coronary artery ectasia presenting with ST-elevation myocardial infarction in a young indigenous man: a case report.

BACKGROUND: Coronary artery ectasia (CAE) is often an incidental finding on angiography, however, patients can present with acute coronary syndrome due to a large thrombus burden requiring treatment with percutaneous coronary intervention or with emergency surgery. CASE SUMMARY: A 26-year-old Indigenous Australian male was admitted with anterior ST-elevation myocardial infarction associated with an out of hospital ventricular fibrillation arrest. Coronary angiography demonstrated thrombotic occlusion of the proximal left anterior descending (LAD) artery with heavy thrombus burden and prominent vascular ectasia of all three coronary arteries. He was managed with surgical thrombectomy and coronary artery bypass graft of his LAD. DISCUSSION: This is the first case of triple CAE in an Indigenous Australian. The case highlights the lack of consensus approach in the management of CAE due to paucity of prospective studies.

Association of Asymptomatic Diastolic Dysfunction Assessed by Left Atrial Strain With Incident Heart Failure.

OBJECTIVES: This study is to establish the association of left atrial reservoir strain (LARS) with incident heart failure (HF), and the impact of substituting LARS for left atrial (LA) volume index (LAVI) in diastolic assessment. BACKGROUND: LARS measures passive LA stretch and is a sensitive marker of left ventricular diastolic dysfunction (DD). The potential contribution of LARS to diastolic assessment is unclear. METHODS: Baseline clinical and echocardiographic assessments were obtained in 758 asymptomatic, community-dwelling elderly subjects (age 70 [interquartile range: 67 to 74] years, 53% women) with nonischemic HF risk factors. LARS-defined DD (LARS-DD) was assessed by speckle-tracking echocardiography, and grades were assigned as normal (>35%), grade 1 (25% to 35%) and grade 2 (≤24%). DD grade using current recommendations was compared with grading using LARS <24% in place of LAVI >34 ml/m2. Patients were followed for up to 2 years for incident HF. RESULTS: LA strain analysis was feasible in 738 (97%) patients; average LARS was 39% (range 34% to 43%). Incident HF was associated with LARS-DD grade; 8 (36%) of those had grade 2+, 14 (10%) had grade 1, and 39 (9%) had normal function (p < 0.001). LARS-DD grade 2+ predicted incident HF after adjustment for clinical and echocardiographic markers (adjusted hazard ratio: 2.5; 95% confidence interval: 1.02 to 6.3; p = 0.049); there was no significant HF risk associated with LARS-DD grade 1. Dichotomized abnormal LARS <24% had an adjusted hazard ratio of 2.9 (95% confidence interval: 1.25 to 6.79; p = 0.013). Substituting LARS for LAVI provided a 75% reduction in indeterminate diastolic function; all were recategorized as normal. There was no increased risk associated normal diastolic function by this grading compared to conventional grading (C-statistic = 0.76 for both models). CONCLUSIONS: LARS-DD grade 2+ is associated with incident HF in the elderly, independent of LAVI. The substitution of LARS for LAVI reduces the number of indeterminate cases without impacting prognosis in normal diastolic function and grade 1 DD.

Echocardiographic Risk Assessment to Guide Screening for Atrial Fibrillation.

BACKGROUND: Although atrial fibrillation (AF) is a significant population health burden, and an avoidable cause of stroke, AF screening remains controversial. The aim of this study was to investigate whether coincidental echocardiography could provide information about patients at risk for AF. METHODS: Asymptomatic participants ≥65 years of age with more than one AF risk factor (N = 445) undergoing echocardiography for risk evaluation were followed over a median of 15 months for incident AF. Left atrial volume index (LAVi), left ventricular (LV) global longitudinal strain (GLS; absolute value), left atrial (LA) strain, and LV mass were measured. During the follow-up period, AF was diagnosed clinically by primary care physicians or by using a single-lead portable electrocardiographic monitoring device (five 60-sec recordings performed by participants over 1 week). RESULTS: AF was diagnosed in 45 patients (10%; mean age, 70.5 ± 4.2 years; 55% women). AF detection was higher in those with LV hypertrophy, GLS < 16%, LAVi > 34 mL/m2, and LA reservoir strain < 34%. GLS, LAVi, and LA reservoir strain were independently associated with AF (P < .05). Those with AF had reduced GLS, higher LAVi, and higher LV mass (P < .05), but LA strain was similar in both groups (P > .05). GLS and LAVi were the strongest predictors, and cut points of 14.3% for GLS and 39 mL/m2 were associated with increased risk for developing AF. Those with all four risk parameters (LV hypertrophy, GLS < 16%, LA reservoir strain < 34%, and LAVi > 34 mL/m2) had a 60% AF detection rate, compared with 7% without these features (P = .004). CONCLUSION: Echocardiography is widely used in patients at risk for AF, and simple LV and LA measurements may be used to enrich the process of AF screening.

Left Atrial Mechanical Dispersion Assessed by Strain Echocardiography as an Independent Predictor of New-Onset Atrial Fibrillation: A Case-Control Study.

BACKGROUND: Left atrial (LA) enlargement is associated with atrial fibrillation (AF), but new-onset AF often occurs in the absence of LA enlargement. AF may be related to myocardial fibrosis, and even though left ventricular fibrosis is associated with mechanical dispersion, this phenomenon is not well studied in AF. We hypothesized that detection of LA dysfunction and mechanical dispersion using strain echocardiography is useful for predicting new-onset AF. METHODS: Baseline echocardiography was performed at entry in 576 community-based participants at risk of heart failure or AF. In this case-control study, we compared 35 individuals with new-onset AF (age 70 ± 4 years; 57% men) over 2 years of follow-up with 35 age- and sex-matched individuals who did not develop AF from the same cohort. Using speckle-tracking echocardiography, we measured the LA strain in each of 12 segments in the two- and four-chamber views. LA mechanical dispersion was defined as the SD of time to peak positive strain corrected by the R-R interval (SD-TPS, %). RESULTS: There was no significant difference in LA volume index (32.5 ± 9.2 mL/m2 vs 29.5 ± 8.3 mL/m2; P = .16); patients with new-onset AF had significantly worse LA pump strain (16.6% ± 4.3% vs 20.6% ± 4.3%; P < .01) and reservoir strain (31.4% ± 7.7% vs 38.0% ± 7.3%; P < .01) than those without AF. SD-TPS was significantly higher in patients with AF than in those without it (6.3% ± 2.3% vs 3.9% ± 1.6%; P < .01). SD-TPS was independently associated with new-onset AF after adjustment for patient characteristics, LA volume, and strain (hazard ratio = 1.26; 95% CI, 1.10-1.45; P < .01). In the nested Cox models, the model based on the LA volume and strain for predicting new onset AF was significantly improved by adding SD-TPS (P < .01). CONCLUSIONS: LA dispersion obtained from strain echocardiography seems to provide incremental information about LA volume and function in the prediction of new-onset AF and warrants testing in a larger study.

Relation of Functional Status to Risk of Development of Atrial Fibrillation.

Identifying patients at risk is now important as there are demonstrable ways to alter disease progression which could potentially prevent atrial fibrillation (AF) and its complications. We sought whether impaired functional capacity was associated with risk of AF, independent of myocardial dysfunction. In this community-based study, asymptomatic participants aged ≥65 years were recruited if they had ≥1 risk factor (e.g., hypertension, diabetes mellitus, and obesity). Participants underwent baseline echocardiography (including measurement of myocardial mechanics) and six-minute walk test. The CHARGE-AF score was used to calculate 5-year risk of developing AF. Receiver operating characteristic curves were used to assess for independent risk factors for AF. A total of 607 patients (age 71 ± 5 years, men 47%) were studied at baseline and followed for at least 6 months. Patients in the higher AF risk groups were older and had increased rates of hypertension, diabetes mellitus, and ischemic heart disease (p <0.05). Greater AF risk was associated with lower exercise capacity, independent of lower mean global longitudinal strain, global circumferential strain, greater mean E/e' ratio, indexed left atrial volume and LV mass. Multivariate linear regression confirmed association of LV and functional capacity parameters with AF risk. Although functional capacity is impaired in AF, this association precedes the onset of AF. In conclusion, poor functional status is associated with AF risk, independent of LV function.

Statin Therapy: Review of Safety and Potential Side Effects.

BACKGROUND: Hydroxymethyl glutaryl coenzyme A reductase inhibitors, commonly called statins, are some of the most commonly prescribed medications worldwide. Evidence suggests that statin therapy has significant mortality and morbidity benefit for both primary and secondary prevention from cardiovascular disease. Nonetheless, concern has been expressed regarding the adverse effects of long term statin use. The purpose of this article was to review the current medical literature regarding the safety of statins. METHODS: Major trials and review articles on the safety of statins were identified in a search of the MEDLINE database from 1980 to 2016, which was limited to English articles. RESULTS: Myalgia is the most common side effect of statin use, with documented rates from 1-10%. Rhabdomyolysis is the most serious adverse effect from statin use, though it occurs quite rarely (less than 0.1%). The most common risk factors for statin-related myopathy include hypothyroidism, polypharmacy and alcohol abuse. Derangement in liver function tests is common, affecting up to 1% of patients; however, the clinical significance of this is unknown. Some statin drugs are potentially diabetogenic and the risk appears to increase in those patients on higher doses. Pitavastatin has not been associated with increased risk of diabetes. Statins have not been proven to increase the risk of malignancy, dementia, mood disorders or acute interstitial nephritis. However, statins do have multiple drug interactions, primarily those which interact with the cytochrome p450 enzyme group. CONCLUSIONS: Overall, statin drugs appear to be safe for use in the vast majority of patients. However, patients with multiple medical co-morbidities are at increased risk of adverse effects from long-term statin use.

Cytogenetic analysis of the pathology of frozen shoulder.

BACKGROUND: Frozen shoulder (FS) is a debilitating musculoskeletal condition with an uncertain etiology and pathogenic mechanism. The aim of this study was to investigate the hypothesis that an alteration in the level of cytokines may disrupt the normal inflammatory and tissue healing process in the shoulder, leading to the development of FS. MATERIALS AND METHODS: A prospective case-control study was undertaken, analyzing patients undergoing arthroscopic treatment of FS and control patients being treated for subacromial bursitis. Synovial biopsies were taken from all subjects. Synovial RNA levels were analyzed using quantitative polymerase chain reaction (qPCR) RESULTS: Thirteen patients with FS were recruited, four of whom were diagnosed with diabetes mellitus, along with 10 control patients. Cytogenetic analysis using qPCR revealed both fibrogenic cytokine matrix metalloproteinase 3 (MMP 3) (1.98×10 (5) vs. 755.0, P=0.068) and inflammatory cytokine interleukin 6 (IL 6) (1679.2 vs. 372.8, P=0.062) to be elevated in FS cases as compared to controls. Comparison between diabetic and non-diabetic patients revealed a decrease in the level of expression of inflammatory cytokine, monocyte colony stimulating factor (M-CSF) (12,496 vs. 305.1, P=0.04) in diabetic FS patients. CONCLUSIONS: The results demonstrate that levels of inflammatory and fibrogenic cytokines are elevated in the synovium of patients with FS compared with controls. This indicates that altered levels of inflammatory cytokines may be associated with the pathogenesis of inflammation evolving into fibrosis, which is the characteristic feature of FS. We have also shown the opposite to be the case in patients with diabetic FS.