Advancing the care of individuals with cancer through innovation & technology: Proceedings from the cardiology oncology innovation summit 2020 and 2021.

As cancer therapies increase in effectiveness and patients' life expectancies improve, balancing oncologic efficacy while reducing acute and long-term cardiovascular toxicities has become of paramount importance. To address this pressing need, the Cardiology Oncology Innovation Network (COIN) was formed to bring together domain experts with the overarching goal of collaboratively investigating, applying, and educating widely on various forms of innovation to improve the quality of life and cardiovascular healthcare of patients undergoing and surviving cancer therapies. The COIN mission pillars of innovation, collaboration, and education have been implemented with cross-collaboration among academic institutions, private and public establishments, and industry and technology companies. In this report, we summarize proceedings from the first two annual COIN summits (inaugural in 2020 and subsequent in 2021) including educational sessions on technological innovations for establishing best practices and aligning resources. Herein, we highlight emerging areas for innovation and defining unmet needs to further improve the outcome for cancer patients and survivors of all ages. Additionally, we provide actionable suggestions for advancing innovation, collaboration, and education in cardio-oncology in the digital era.

Transcatheter aortic valve intervention in patients with cancer.

The prevalence of concurrent cancer and severe aortic stenosis (AS) is increasing due to an ageing population. In addition to shared traditional risk factors for AS and cancer, patients with cancer may be at increased risk for AS due to off-target effects of cancer-related therapy, such as mediastinal radiation therapy (XRT), as well as shared non-traditional pathophysiological mechanisms. Compared with surgical aortic valve replacement, major adverse events are generally lower in patients with cancer undergoing transcatheter aortic valve intervention (TAVI), especially in those with history of mediastinal XRT. Similar procedural and short-to-intermediate TAVI outcomes have been observed in patients with cancer as compared with no cancer, whereas long-term outcomes are dependent on cancer survival. Considerable heterogeneity exists between cancer subtypes and stage, with worse outcomes observed in those with active and advanced-stage disease as well as specific cancer subtypes. Procedural management in patients with cancer poses unique challenges and thus requires periprocedural expertise and close collaboration with the referring oncology team. The decision to ultimately pursue TAVI involves a multidisciplinary and holistic approach in assessing the appropriateness of intervention. Further clinical trial and registry studies are needed to better appreciate outcomes in this population.

Coronary revascularisation outcomes in patients with cancer.

Cancer and coronary artery disease (CAD) overlap in traditional risk factors as well as molecular mechanisms underpinning the development of these two disease states. Patients with cancer are at increased risk of developing CAD, representing a high-risk population that are increasingly undergoing coronary revascularisation. Over 1 in 10 patients with CAD that require revascularisation with either percutaneous coronary intervention or coronary artery bypass grafting have either a history of cancer or active cancer. These patients are typically older, have more comorbidities and have more extensive CAD compared with patients without cancer. Haematological abnormalities with competing risks of thrombosis and bleeding pose further unique challenges during and after revascularisation. Management of patients with concurrent cancer and CAD requiring revascularisation is challenging as these patients carry a higher risk of morbidity and mortality compared with those without cancer, often driven by the underlying cancer and associated comorbidities. However, due to variability by different types and stages of cancer, revascularisation outcomes are specific to cancer characteristics such as the timing of onset, cancer subtype and site, stage, presence of metastases, and cancer-related therapies received. Recent studies have provided insights into defining revascularisation outcomes, procedural considerations and best practices in managing patients with cancer. Nevertheless, many gaps remain that require further studies to inform clinical best practices in this population.

Lack of Association Between Neurohormonal Blockade and Survival in Transthyretin Cardiac Amyloidosis.

Background Despite the belief that heart failure therapies are not effective in transthyretin cardiac amyloidosis, data are limited. We tested the association of neurohormonal blockade use with survival. Methods and Results A total of 309 consecutive patients with transthyretin cardiac amyloidosis were identified. Medication inventory was obtained at baseline and subsequent visits. Exposure included a neurohormonal blockade class (ß-blocker [ßB], angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and mineralocorticoid antagonist) at baseline and subsequent visits. ßB was modeled as baseline use, time-varying use, and in an inverse probability treatment weighted model. Primary outcome was all-cause mortality analyzed with adjusted Cox proportional hazards models. Continuing compared with stopping ßB during follow-up was tested. Mean age was 73.2 years, 84.1% were men, and 17.2% had atrial fibrillation/flutter at baseline. At the time of study entry, 49.8% were on ßBs, 35.0% were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 23.9% were on mineralocorticoid antagonists. For the total cohort, there was a trend toward harm in the unadjusted model for baseline ßB use, but this was neutral after adjustment. When ßB use was analyzed as a time-varying exposure, there was no association with mortality. ßB discontinuation was associated with decreased mortality for the total cohort. Findings were consistent in inverse probability treatment weighted models. For angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or mineralocorticoid antagonist use, there was no association with mortality after adjustment for the total cohort. Conclusions There was no association of neurohormonal blockade use with survival in transthyretin cardiac amyloidosis. For the total cohort, deprescribing ßB may be associated with improved survival. Additional studies are needed to confirm these findings.

A new classification of cardio-oncology syndromes.

Increasing evidence suggests a multifaceted relationship exists between cancer and cardiovascular disease (CVD). Here, we introduce a 5-tier classification system to categorize cardio-oncology syndromes (COS) that represent the aspects of the relationship between cancer and CVD. COS Type I is characterized by mechanisms whereby the abrupt onset or progression of cancer can lead to cardiovascular dysfunction. COS Type II includes the mechanisms by which cancer therapies can result in acute or chronic CVD. COS Type III is characterized by the pro-oncogenic environment created by the release of cardiokines and high oxidative stress in patients with cardiovascular dysfunction. COS Type IV is comprised of CVD therapies and diagnostic procedures which have been associated with promoting or unmasking cancer. COS Type V is characterized by factors causing systemic and genetic predisposition to both CVD and cancer. The development of this framework may allow for an increased facilitation of cancer care while optimizing cardiovascular health through focused treatment targeting the COS type.

The association between heart failure and incident cancer in women: an analysis of the Women's Health Initiative.

AIMS: There is conflicting evidence whether heart failure (HF) is a risk factor for incident cancer. Despite population-based cohorts demonstrating this association, an analysis of the Physician's Health Study found no association in a cohort of mostly healthy males. We investigated the association of HF with incident cancer among a large cohort of post-menopausal women. METHODS AND RESULTS: A prospective cohort study of 146 817 post-menopausal women age 50 to 79 years enrolled in the Women's Health Initiative from 1993-1998, and followed through 2015. The primary exposure was adjudicated incident HF diagnosis, including preserved and reduced ejection fraction in a sub-cohort. The primary outcome was adjudicated incident total and site-specific cancers. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazard regression models. Over a median follow-up of 8.4 years, 3272 and 17 474 women developed HF and cancer, respectively. HF developed in 235 women prior to cancer. HF was associated with subsequent incident cancer [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.11-1.48]. Associations were observed for obesity-related cancers (HR 1.24, 95% CI 1.02-1.51), as well as lung and colorectal cancers (HR 1.58, 95% CI 1.09-2.30 and HR 1.52, 95% CI 1.02-2.27, respectively). HF with preserved ejection fraction (HR 1.34, 95% CI 1.06-1.67), but not HF reduced ejection fraction (HR 0.99, 95% CI 0.74-1.34), was associated with total cancer. CONCLUSION: Heart failure was associated with an increase in cancer diagnoses in post-menopausal women. This association was strongest for lung cancer. Further research is needed to appreciate the underlying mechanisms responsible for this association.

Diuretic Dose and NYHA Functional Class Are Independent Predictors of Mortality in Patients With Transthyretin Cardiac Amyloidosis.

BACKGROUND: With increasing diagnoses and available treatment options for transthyretin amyloidosis cardiomyopathy (ATTR-CM), risk stratification of ATTR-CM patients is imperative. OBJECTIVES: We hypothesized that diuretic dose and New York Heart Association (NYHA) functional class are independent predictors of mortality in ATTR-CM and would be incrementally additive to existent risk scores. METHODS: Consecutive ATTR-CM patients referred to a single center were identified. Adjusted Cox proportional hazards models determined the association between diuretic dose (furosemide equivalent in mg/kg) at time of diagnosis and the primary outcome of all-cause mortality. The incremental value of adding diuretic dose and NYHA functional class to existing ATTR-CM risk scores was assessed for discrimination and calibration. RESULTS: 309 patients were identified, with mean age 73.2 ± 9.8 years, 84.1% male, and 66% wild type. Daily mean diuretic dose was 0.6 ± 1.0 mg/kg and significantly associated with all-cause mortality (unadjusted hazard ratio: 2.12 per 1-mg/kg increase, [95% confidence interval: 1.71 to 2.61] and fully adjusted hazard ratio: 1.43 [95% confidence interval: 1.06 to 1.93]). Testing previously published ATTR risk scores, adding diuretic dose as categories (0 mg/kg, >0 to 0.5 mg/kg, >0.5 to 1 mg/kg, and >1 to 2 mg/kg) improved the area under the curve of the Mayo risk score from 0.693 to 0.767 and the UK risk score from 0.711 to 0.787 while preserving calibration. Adding NYHA functional class further improved the area under the curve to 0.798 and 0.816, respectively. CONCLUSIONS: Diuretic dose and NYHA functional class are independent predictors of mortality in ATTR-CM patients and provide incremental value to existing ATTR-CM risk scores.

Moderate or severe valvular heart disease and outcomes in allogeneic stem cell transplantation.

BACKGROUND: A Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) was previously developed showing that multiple comorbidities including moderate or greater valvular heart disease to be predictors of non-relapse mortality after allogeneic HCT. However, detailed description of the impact of valve disease on outcomes is lacking. METHODS: Among a large cohort of patients given allogeneic HCT between 2000 and 2017, we identified 21 patients with moderate or severe valvular disease. We also identified a cohort of 42 controls matched on age and HCT-CI score. The primary outcome was all-cause mortality, with censoring at two years of follow-up. Secondary outcomes included mortality without relapse, duration of index admission, number of readmissions, increase in creatinine and peak troponin. RESULTS: Non-myeloablative regimens were more common in the valve disease cohort compared to controls (86% vs 54% p = 0.012). Valvular disease was associated with increased all-cause mortality with adjusted hazard ratio of 2.17 (CI 1.08-4.34, p = 0.029) and for non-relapse mortality with adjusted hazard ratio of 2.53 (CI 1.16-5.52, p = 0.020). In the valve disease cohort, creatinine increased by 1.6 vs 0.9 mg/dL (p = 0.003) and peak troponin by 1.6 vs 0.3 ng/mL (p = 0.05) compared to controls. There was no difference in readmissions or length of stay when accounting for outpatient treatment. CONCLUSIONS: Despite having similar pre-procedure risk factors and undergoing less aggressive chemotherapy regimens, patients with moderate valvular disease or greater, most of whom did not meet current guideline recommendations for repair, had worse non-relapse related outcomes with higher mortality, renal and myocardial injury.

Cardiovascular Disease and Cancer: Is There Increasing Overlap?

PURPOSE OF REVIEW: Cancer and cardiovascular disease are the leading causes of mortality in the USA. In this review, we highlight these shared disease pathways and provide a framework for a systems-based approach to reduce overall risk burden. RECENT FINDINGS: From traditional risk factors such as age and tobacco use to more recently recognized entities including clonal hematopoiesis, we are gaining insights into shared mechanisms. Because of these overlapping risks, providers on each level of patient care (primary care providers, cardiologists, oncologists) need to recognize and reduce these underlying risk factors. There is significant overlap in the epidemiology and risk factors for the development of cardiovascular disease and cancer, providing opportunities for joint risk factor modification.