The cancer patient and cardiology

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long-term follow-up strategies for patients at risk of cancer therapy-related cardiotoxicities. Research to better define strategies for early identification, follow-up and management is highly necessary. Although the academic cardio-oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross-discipline interactions and help in the design and funding of cardio-oncology trials. The overarching goals of cardio-oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology.</p

Noninvasive characterization of patients with monomorphic ventricular tachycardia and ventricular fibrillation using the signal-averaged electrocardiogram. A study on late potentials and spectral turbulence in patients with ischemic heart disease and in healthy subjects.

Many people die suddenly from sustained ventricular tachyarrhythmias caused by ischemic heart disease, and the sudden death may be the first presentation of heart disease. If the patients at risk of ventricular tachyarrhythmia could be identified, some patients may be saved.The signal-averaged ECGs of 62 patients with spontaneous sustained monomorphic ventricular tachycardia (MVT), 64 survivors of cardiac arrest with ventricular fibrillation (VF), and 82 patients without ventricular arrhythmia who all had ischemic heart disease but no bundle branch block were compared. The patients with MVT frequently had a low ventricular ejection fraction and were significantly more late potential-positive and spectral turbulence-positive, which indicates that a more severe underlying substrate is necessary for development of MVT than for VF. The best variables of the signal-averaged ECG for identifying patients that had already suffered MVT vs VF were the width of the QRS complex measured as the filtered QRS duration and as the total QRS duration in the spectral analysis and the filtered QRS duration, respectively.The presence of a bundle branch block in patients with ischemic heart disease will per definition cause a wide QRS 3 120 ms and is known to further increase the risk of cardiac mortality. Patients with right bundle branch block (n=15) and with left bundle branch block (n=28) without spontaneous ventricular arrhythmias were late potential-positive in 27% and 50%, respectively, and spectral turbulence-positive in 80% and 79%, respectively. There were differences in the time domain analogous variables of the individual X, Y, Z orthogonal leads of the signal-averaged ECG between right and left bundle branch blocks. Patients with both spontaneous sustained MVT (n=13) or cardiac arrest with VF (n=6) and a bundle branch block were compared with control patients (n=38), matched 2:1 for each arrhythmia patient according to type of block, age, gender and previous myocardial infarction. There was no significant difference between patients with bundle branch block and VF and matched controls in any variable of the signal-averaged ECG, but the patients with MVT were more positive in variables of spectral analysis from individual X, Y, Z leads.In 121 subjects (55 men and 66 women; mean age 50 years) randomly selected without known heart disease and without bundle branch block, 7% were late potential-positive and 7% were spectral turbulence-positive. Almost all were completely normal at echocardiographic examination and during 24-hour ECG recording. The men had a significantly longer filtered QRS duration than women, which correlated with body surface area and intracardiac dimensions at echocardiography, but women had a longer QT interval in the 12 lead ECG. The numerical short-term reproducibility of the signal-averaged ECG variables was measured in the 121 healthy subjects. It was found to be good for time-domain and time-domain analogous variables but varied in spectral turbulence variables and was not different from short-term reproducibility in the 43 patients with bundle branch block or from long-term reproducibility. The reproducibility was affected by the noise level, but to a lesser extent by gender and age. If the spectral turbulence variable interslice-correlation standard deviation was replaced by the mean peaks per slice, the diagnostic reproducibility of spectral turbulence analysis improved substantially

Drug-induced blood pressure increase – recommendations for assessment in clinical and non-clinical studies

<p><b>Introduction:</b> Changes in blood pressure (BP) are now proactively examined throughout the drug development process as an integral aspect of safety monitoring. This is because hypertension is a very strong risk factor for cardiovascular events and drug-induced increases in BP have attracted increased regulatory attention. However, there is currently no guidance from regulatory agencies on the minimum BP data required for submissions, and there are no specific criteria for what constitutes a safety signal for increased BP in non clinical studies.</p> <p><b>Areas covered:</b> Evaluation of BP increases through the drug discovery and development process.</p> <p><b>Expert opinion:</b> Research into the effects of drugs should begin before clinical development is initiated and continue throughout the clinical trial program. Non clinical studies should inform a benefit–risk analysis that will aid decision-making of whether to enter the drug into Phase I development. The degree of acceptable risk will vary according to the therapy area, treatment indication and intended population for the new drug, and the approach to BP assessment and risk mitigation should be tailored accordingly. However, BP monitoring should always be included in clinical trials, and data collected from multiple studies, to convincingly prove or refute a suspicion of BP effects.</p

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications