Burden and prognostic impact of cardiovascular disease in patients with cancer.

The number of patients at the intersection of cancer and cardiovascular disease (CVD) is increasing, reflecting ageing global populations, rising burden of shared cardiometabolic risk factors, and improved cancer survival. Many cancer treatments carry a risk of cardiotoxicity. Baseline cardiovascular risk assessment is recommended in all patients with cancer and requires consideration of individual patient risk and the cardiotoxicity profile of proposed anticancer therapies. Patients with pre-existing CVD are potentially at high or very high risk of cancer-therapy related cardiovascular toxicity. The detection of pre-existing CVD should prompt cardiac optimisation and planning of surveillance during cancer treatment. In patients with severe CVD, the risk of certain cancer therapies may be prohibitively high. Such decisions require multidisciplinary discussion with consideration of alternative anti-cancer therapies, risk-benefit assessment, and patient preference. Current practice is primarily guided by expert opinion and data from select clinical cohorts. There is need for development of a stronger evidence base to guide clinical practice in cardio-oncology. The establishment of multicentre international registries and national-level healthcare data linkage projects are important steps towards facilitating enrichment of cardio-oncology research programmes. In this narrative review, we consider epidemiological trends of cancer and CVD comorbidities and the impact of their co-occurrence on clinical outcomes, current approach to supporting cancer patients with pre-existing CVD and gaps in existing knowledge.

Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.

OBJECTIVES: To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer. METHODS: Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics. RESULTS: We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk. CONCLUSIONS: Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.

Multimodality Imaging for Cardiotoxicity: State of the Art and Future Perspectives.

ABSTRACT: Modern cancer therapies have significantly improved survival leading to a growing population of cancer survivors. Similarly, both conventional and newer treatments are associated with a spectrum of cardiovascular disorders with potential long-term sequelae. Prompt detection and treatment of these complications is, therefore, pivotal to enable healthy survivorship and reduce cardiovascular morbidity. Advanced multimodality imaging is a valuable tool for stratifying patient risk, identifying cardiovascular toxicity during and after therapy, and predicting recovery. This review summarizes the potential cardiotoxic complications of anticancer therapies and the multimodality approaches available in each case with special focus on newer techniques and the added value of biomarkers ultimately leading to earlier diagnosis and better prognostication.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Role of cardiovascular magnetic resonance imaging in cardio-oncology.

Advances in cancer therapy have led to significantly longer cancer-free survival times over the last 40 years. Improved survivorship coupled with increasing recognition of an expanding range of adverse cardiovascular effects of many established and novel cancer therapies has highlighted the impact of cardiovascular disease in this population. This has led to the emergence of dedicated cardio-oncology services that can provide pre-treatment risk stratification, surveillance, diagnosis, and monitoring of cardiotoxicity during cancer therapies, and late effects screening following completion of treatment. Cardiovascular imaging and the development of imaging biomarkers that can accurately and reliably detect pre-clinical disease and enhance our understanding of the underlying pathophysiology of cancer treatment-related cardiotoxicity are becoming increasingly important. Multi-parametric cardiovascular magnetic resonance (CMR) is able to assess cardiac structure, function, and provide myocardial tissue characterization, and hence can be used to address a variety of important clinical questions in the emerging field of cardio-oncology. In this review, we discuss the current and potential future applications of CMR in the investigation and management of cancer patients.

Advanced Imaging Modalities to Monitor for Cardiotoxicity.

OPINION STATEMENT: Early detection and treatment of cardiotoxicity from cancer therapies is key to preventing a rise in adverse cardiovascular outcomes in cancer patients. Over-diagnosis of cardiotoxicity in this context is however equally hazardous, leading to patients receiving suboptimal cancer treatment, thereby impacting cancer outcomes. Accurate screening therefore depends on the widespread availability of sensitive and reproducible biomarkers of cardiotoxicity, which can clearly discriminate early disease. Blood biomarkers are limited in cardiovascular disease and clinicians generally still use generic screening with ejection fraction, based on historical local expertise and resources. Recently, however, there has been growing recognition that simple measurement of left ventricular ejection fraction using 2D echocardiography may not be optimal for screening: diagnostic accuracy, reproducibility and feasibility are limited. Modern cancer therapies affect many myocardial pathways: inflammatory, fibrotic, metabolic, vascular and myocyte function, meaning that multiple biomarkers may be needed to track myocardial cardiotoxicity. Advanced imaging modalities including cardiovascular magnetic resonance (CMR), computed tomography (CT) and positron emission tomography (PET) add improved sensitivity and insights into the underlying pathophysiology, as well as the ability to screen for other cardiotoxicities including coronary artery, valve and pericardial diseases resulting from cancer treatment. Delivering screening for cardiotoxicity using advanced imaging modalities will however require a significant change in current clinical pathways, with incorporation of machine learning algorithms into imaging analysis fundamental to improving efficiency and precision. In the future, we should aspire to personalized rather than generic screening, based on a patient's individual risk factors and the pathophysiological mechanisms of the cancer treatment they are receiving. We should aspire that progress in cardiooncology is able to track progress in oncology, and to ensure that the current 'one size fits all' approach to screening be obsolete in the very near future.

MRI for patients with cardiac implantable electronic devices: simplifying complexity with a 'one-stop' service model.

BACKGROUND: Patients with cardiac pacemakers and defibrillators are disadvantaged because of poor access to MRI scans, leading to late and misdiagnosis particularly for cancer and neurological disease. New technology allied to tested protocols now allows safe MRI scanning of such patients; however, logistical barriers persist. AIM: To deliver a streamlined sustainable service that provides timely MRI scans to patients with cardiac implantable electronic devices (CIEDs). METHODS: Patients requested a 'one-stop' service for MRI, whereby devices could be reprogrammed and scans acquired at a single location and visit. To provide this 'one-stop' service, we trained a team including administrators, physicians, cardiac physiologists and radiographers. A standard protocol was used to prevent unnecessary request refusals and delays to scheduling. Service volume, waiting time and safety were analysed 6 months before and 2 years after service redesign. Waiting times for internal and external inpatient referrals plus time to treatment for patients on a cancer pathway were analysed. RESULTS: 215 MRI scans were performed over 2 years. After service redesign, MRI provision increased six-fold to 20 times the national average with reduced waiting time from 60 to 15 days and no adverse events. Departmental throughput was maintained. 85 (40%) referrals were external. 41 (19%) inpatients were scanned, reducing bed-stay by 3 days for internal referrals. 24 (11%) scans were for suspected cancer, 83% allowed treatment within the national standard of 62 days. There was no preintervention service for either inpatients or suspected cancer investigation. CONCLUSION: Implementation of a 'one-stop' service model to provide MRI for patients with CIEDs is safe, streamlined, scalable and has reduced delays making economic and clinical sense. Protocols and checklists are available at mrimypacemaker.com.

Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis.

BACKGROUND: The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. METHODS AND RESULTS: Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). CONCLUSIONS: There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors.

T1 mapping: non-invasive evaluation of myocardial tissue composition by cardiovascular magnetic resonance.

Cardiovascular magnetic resonance is an important tool for patient care and is the best test for myocardial structure and function. Ischemia and scar imaging also provide key insights and focus attention on heart muscle - the site of most cardiac diseases. New ways of measuring abnormal muscle have been developed, including T1 mapping. Abnormal signal can be distinguished either without contrast (native T1), or post-contrast (extracellular volume measurement). Large changes occur in rare diseases (cardiac amyloidosis, Anderson-Fabry disease and iron overload) even at an early stage, while more subtle changes are seen in diffuse fibrosis where a robust test would be of major impact. This review presents the potential future clinical utility of T1 mapping - a technology to watch.

Patient-accessible tool for shared decision making in cardiovascular primary prevention: balancing longevity benefits against medication disutility.

BACKGROUND: Primary prevention guidelines focus on risk, often assuming negligible aversion to medication, yet most patients discontinue primary prevention statins within 3 years. We quantify real-world distribution of medication disutility and separately calculate the average utilities for a range of risk strata. METHOD AND RESULTS: We randomly sampled 360 members of the general public in London. Medication aversion was quantified as the gain in lifespan required by each individual to offset the inconvenience (disutility) of taking an idealized daily preventative tablet. In parallel, we constructed tables of expected gain in lifespan (utility) from initiating statin therapy for each age group, sex, and cardiovascular risk profile in the population. This allowed comparison of the widths of the distributions of medication disutility and of group-average expectation of longevity gain. Observed medication disutility ranged from 1 day to >10 years of life being required by subjects (median, 6 months; interquartile range, 1-36 months) to make daily preventative therapy worthwhile. Average expected longevity benefit from statins at ages ≥50 years ranges from 3.6 months (low-risk women) to 24.3 months (high-risk men). CONCLUSION: We can no longer assume that medication disutility is almost zero. Over one-quarter of subjects had disutility exceeding the group-average longevity gain from statins expected even for the highest-risk (ie, highest-gain) group. Future primary prevention studies might explore medication disutility in larger populations. Patients may differ more in disutility than in prospectively definable utility (which provides only group-average estimates). Consultations could be enriched by assessing disutility and exploring its reasons.