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.

Simplified rules-based tool to facilitate the application of up-to-date management recommendations in cardio-oncology.

BACKGROUND: Millions of cancer survivors are at risk of cardiovascular diseases, a leading cause of morbidity and mortality. Tools to potentially facilitate implementation of cardiology guidelines, consensus recommendations, and scientific statements to prevent atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases are limited. Thus, inadequate utilization of cardiovascular medications and imaging is widespread, including significantly lower rates of statin use among cancer survivors for whom statin therapy is indicated. METHODS: In this methodological study, we leveraged published guidelines documents to create a rules-based tool to include guidelines, expert consensus, and medical society scientific statements relevant to point of care cardiovascular disease prevention in the cardiovascular care of cancer survivors. Any overlap, redundancy, or ambiguous recommendations were identified and eliminated across all converted sources of knowledge. The integrity of the tool was assessed with use case examples and review of subsequent care suggestions. RESULTS: An initial selection of 10 guidelines, expert consensus, and medical society scientific statements was made for this study. Then 7 were kept owing to overlap and revisions in society recommendations over recent years. Extensive formulae were employed to translate the recommendations of 7 selected guidelines into rules and proposed action measures. Patient suitability and care suggestions were assessed for several use case examples. CONCLUSION: A simple rules-based application was designed to provide a potential format to deliver critical cardiovascular disease best-practice prevention recommendations at the point of care for cancer survivors. A version of this tool may potentially facilitate implementing these guidelines across clinics, payers, and health systems for preventing cardiovascular diseases in cancer survivors. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05377320.

Patient similarity and other artificial intelligence machine learning algorithms in clinical decision aid for shared decision-making in the Prevention of Cardiovascular Toxicity (PACT): a feasibility trial design.

BACKGROUND: The many improvements in cancer therapies have led to an increased number of survivors, which comes with a greater risk of consequent/subsequent cardiovascular disease. Identifying effective management strategies that can mitigate this risk of cardiovascular complications is vital. Therefore, developing computer-driven and personalized clinical decision aid interventions that can provide early detection of patients at risk, stratify that risk, and recommend specific cardio-oncology management guidelines and expert consensus recommendations is critically important. OBJECTIVES: To assess the feasibility, acceptability, and utility of the use of an artificial intelligence (AI)-powered clinical decision aid tool in shared decision making between the cancer survivor patient and the cardiologist regarding prevention of cardiovascular disease. DESIGN: This is a single-center, double-arm, open-label, randomized interventional feasibility study. Our cardio-oncology cohort of > 4000 individuals from our Clinical Research Data Warehouse will be queried to identify at least 200 adult cancer survivors who meet the eligibility criteria. Study participants will be randomized into either the Clinical Decision Aid Group (where patients will use the clinical decision aid in addition to current practice) or the Control Group (current practice). The primary endpoint of this study is to assess for each patient encounter whether cardiovascular medications and imaging pursued were consistent with current medical society recommendations. Additionally, the perceptions of using the clinical decision tool will be evaluated based on patient and physician feedback through surveys and focus groups. This trial will determine whether a clinical decision aid tool improves cancer survivors' medication use and imaging surveillance recommendations aligned with current medical guidelines. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05377320.

Connected Health Innovation Research Program (C.H.I.R.P.): A bridge for digital health and wellness in cardiology and oncology.

Study objective: Cancer and heart disease are leading causes of mortality, and cardio-oncology is emerging as a new field addressing the cardiovascular toxicities related to cancer and cancer therapy. Interdisciplinary research platforms that incorporate digital health to optimize cardiovascular health and wellness in cancer survivors are therefore needed as we advance in the digital era. Our goal was to develop the Connected Health Innovation Research Program (C.H.I.R.P.) to serve as a foundation for future integration and assessments of adoption and clinical efficacy of digital health tools for cardiovascular health and wellness in the general population and in oncology patients. Design/setting/participants: Partner companies were identified through the American Medical Association innovation platform, as well as LinkedIn and direct contact by our team. Company leaders met with our team to discuss features of their technology or software. Non-disclosure agreements were signed and data were discussed and obtained for descriptive or statistical analysis. Results: A suite of companies with technologies focused on wellness, biometrics tracking, audio companions, oxygen saturation, weight trends, sleep patterns, heart rate variability, electrocardiogram patterns, blood pressure patterns, real-time metabolism tracking, instructional video modules, or integration of these technologies into electronic health records was collated. We formed an interdisciplinary research team and established an academia-industry collaborative foundation for connecting patients with wellness digital health technologies. Conclusions: A suite of software and device technologies accessible to the cardiology and oncology population has been established and will facilitate retrospective, prospective, and case research studies assessing adoption and clinical efficacy of digital health tools in cardiology/oncology.

The beneficial effect of weight reduction on adverse cardiovascular outcomes following bariatric surgery is attenuated in patients with obstructive sleep apnea.

Weight loss after bariatric surgery is associated with reduction in adverse cardiovascular outcomes; however, the impact of obstructive sleep apnea (OSA) on reduction of cardiovascular outcomes after bariatric surgery in morbidly obese patients is not known. We retrospectively assessed differences in cardiovascular events after laparoscopic adjustable gastric banding (LAGB)-induced weight loss in patients with and without OSA before and after propensity score matching for age, sex, body mass index (BMI), and major comorbidities between the two groups and determined predictors of poor outcomes. OSA was present in 222 out of 830 patients (27 per cent) who underwent LAGB between 2001 and 2011. Despite a similar reduction in BMI (20.0 and 20.8 per cent), a significantly higher percentage of cardiovascular events were observed in patients with than without OSA (35.6 vs 6.9 per cent; p < 0.001) at 3 years (mean follow-up 6.0 ± 3.2; range: 0.5 to 13 years). The differences in the cumulative endpoint of new onset stroke, heart failure, myocardial infarction, venous thrombosis, and pulmonary embolism between the OSA and non-OSA groups were maintained after propensity matching. Patients with OSA treated with continuous positive airway pressure (CPAP) during sleep [n = 66] had lower cardiovascular event rates at 30 months compared with those not treated (p < 0.041). OSA (hazard ratio: 6.92, 95% CI: 3.39-14.13, p < 0.001) remained an independent predictor of cardiovascular events after multivariate analysis. Thus, patients with OSA, despite a similar initial weight loss after LAGB, had a higher incidence of cardiovascular events compared with a propensity-matched group without OSA. Treatment with CPAP appears to reduce such events.

Comparative Effectiveness of Hybrid Ablation Versus Endocardial Catheter Ablation Alone in Patients With Persistent Atrial Fibrillation.

OBJECTIVES: The outcomes of hybrid ablation versus endocardial catheter ablation alone were evaluated in patients with persistent and long-standing persistent atrial fibrillation (AF). BACKGROUND: Variable outcomes exist following endocardial catheter ablation in medically refractory patients with persistent AF. A hybrid epicardial-endocardial approach has emerged as an alternative to endocardial ablation. METHODS: In 133 consecutive patients, 69 received endocardial ablation alone (pulmonary vein isolation and radiofrequency catheter ablation [endo group]) and 64 received endocardial catheter ablation and epicardial ablation (hybrid group). Recurrence was defined as any arrhythmia following the 3-month blanking period. RESULTS: Patients were followed for a median of 16 months. The hybrid and endo groups were similar in age (61 ± 10 years vs. 62 ± 8 years), body mass index (35 ± 6 kg/m2 vs. 35 ± 7 kg/m2), CHA2D2-VASc score (2 ± 1 vs. 2 ± 1), and ejection fraction (54 ± 11% vs. 53 ± 8%). The hybrid group had longer AF duration (median [interquartile range (IQR)] (12 months [IQR: 8 to 28 months] vs. 7 months [IQR: 5 to 12 months]; p < 0.001) and more previous ablations (58% vs. 25%; p < 0.001). Both groups had similar antiarrhythmic drug use at follow-up (55% vs. 48%). The hybrid group was less likely to have recurrence (37% vs. 58%; p = 0.013) and repeat ablation (9% vs. 26%; p = 0.012), and had an AF-free survival of 72% versus 51% (p = 0.01). CONCLUSIONS: Among patients with persistent AF, hybrid ablation is associated with less AF recurrence and fewer re-do ablations. Prospective large-scale randomized trials are needed to validate these results.

Identifying the third dimension in 2D fluoroscopy to create 3D cardiac maps.

Three-dimensional cardiac mapping is important for optimal visualization of the heart during cardiac ablation for the treatment of certain arrhythmias. However, many hospitals and clinics worldwide cannot afford the high cost of the current mapping systems. We set out to determine if, using predefined algorithms, comparable 3D cardiac maps could be created by a new device that relies on data generated from single-plane fluoroscopy and patient recording and monitoring systems, without the need for costly equipment, infrastructure changes, or specialized catheters. The study included phantom and animal experiments to compare the prototype test device, Navik 3D, with the existing CARTO 3 System. The primary endpoint directly compared: (a) the 3D distance between the Navik 3D-simulated ablation location and the back-projected ground truth location of the pacing and mapping catheter electrode, and (b) the same distance for CARTO. The study's primary objective was considered met if the 95% confidence lower limit was greater than 0.75% for the Navik 3D-CARTO difference between the 2 distances, or less than or equal to 2 mm. Study results showed that the Navik 3D performance was equivalent to the CARTO system, and that accurate 3D cardiac maps can be created using data from equipment that already exists in all electrophysiology labs.

Implantable cardioverter defibrillators in diabetics: efficacy and safety in patients at risk of sudden cardiac death.

Diabetes mellitus is a major risk factor for arrhythmogenesis and is associated with a two-fold increase in all-cause mortality and a four-fold increase in cardiovascular mortality including sudden cardiac death when compared with nondiabetics. Implantable cardioverter defibrillators (ICD) have been shown to effectively reduce arrhythmic death and all-cause mortality in patients with severe myocardial dysfunction. With a high competing risk of nonarrhythmic cardiac and noncardiac death, survival benefit of ICD in patients with diabetes mellitus could be reduced, but the subanalysis of diabetic patients in randomized clinical trials provides reassurance regarding a similar beneficial survival effect of ICD and cardiac resynchronization therapy in diabetics, as observed in the overall population with advanced heart disease. In this article, the authors highlight some of the clinical issues related to diabetes, summarize the data on the efficacy of ICD in diabetics when compared with nondiabetics and discuss concerns related to ICD implantation in patients with diabetes.

Bachmann's bundle and coronary sinus ostial pacing accentuate left atrial electrical dyssynchrony in an acute canine model.

INTRODUCTION: In patients with intraatrial conduction delay and sinus node (SN) dysfunction, pacing Bachmann's bundle (BBR) and coronary sinus ostium (CSO) has been suggested to achieve atrial resynchronization with potential beneficial impact on atrial fibrillation and diastolic heart failure. Clinical studies have not shown superiority of one approach. METHODS AND RESULTS: We studied electrical activation sequence in an open-chest acute canine model of normal atrial function in 8 mongrel dogs under general anesthesia. Bipolar plunge electrodes were distributed over the surface of the atria during unifocal pacing, and intracardiac activation sequence was observed. SN pacing resulted in near-simultaneous activation at midline sites (BBR and CSO); the left atrium (LA) was activated by anterior and posterior wavefronts simultaneously propagating septally to laterally and meeting at the low-lateral perimitral LA. Right atrial appendage (RAA) pacing created intra-RA conduction delay and delayed onset of LA activation. Pacing from RAA, CSO, and BBR resulted in nonsimultaneous activation at midline sites and produced an anteroposterior gradient of LA activation. This phenomenon was seen to the greatest degree with midline pacing and shifted the site of latest activation away from the low-lateral perimitral LA in all pacing configurations except SN pacing. CONCLUSION: Pacing-induced intra-LA activation dispersion is enhanced with midline atrial pacing, and secondarily shifts the site of latest activation away from the lateral mitral annulus. Measuring atrial activation times to the low-lateral perimitral LA can underestimate the degree of atrial dyssynchrony and be misinterpreted as atrial synchrony. Establishing clinical impact requires evaluation of human data.

Clinical feasibility of exercise-based A-V interval optimization for cardiac resynchronization: a pilot study.

BACKGROUND: One-third of eligible patients fail to respond to cardiac resynchronization therapy (CRT). Current methods to "optimize" the atrio-ventricular (A-V) interval are performed at rest, which may limit its efficacy during daily activities. We hypothesized that low-intensity cardiopulmonary exercise testing (CPX) could identify the most favorable physiologic combination of specific gas exchange parameters reflecting pulmonary blood flow or cardiac output, stroke volume, and left atrial pressure to guide determination of the optimal A-V interval. METHODS: We assessed relative feasibility of determining the optimal A-V interval by three methods in 17 patients who underwent optimization of CRT: (1) resting echocardiographic optimization (the Ritter method), (2) resting electrical optimization (intrinsic A-V interval and QRS duration), and (3) during low-intensity, steady-state CPX. Five sequential, incremental A-V intervals were programmed in each method. Assessment of cardiopulmonary stability and potential influence on the CPX-based method were assessed. RESULTS: CPX and determination of a physiological optimal A-V interval was successfully completed in 94.1% of patients, slightly higher than the resting echo-based approach (88.2%). There was a wide variation in the optimal A-V delay determined by each method. There was no observed cardiopulmonary instability or impact of the implant procedure that affected determination of the CPX-based optimized A-V interval. CONCLUSIONS: Determining optimized A-V intervals by CPX is feasible. Proposed mechanisms explaining this finding and long-term impact require further study.

Three-dimensional electroanatomic mapping of the coronary veins during cardiac resynchronization therapy implant: feasibility and possible applications.

PURPOSE: Left ventricular (LV) electrical activation pattern could determine optimal LV lead placement site during cardiac resynchronization therapy (CRT) device implant. We sought to determine the feasibility of using EnSite NavX™ electroanatomic mapping system (St. Jude Medical Inc., St. Paul, MN) to assess LV electrical activation during CRT implant. METHODS: Patients (n = 32; NYHA III, LVEF <35%, QRSd >120 ms) underwent NavX™ mapping during CRT implant. Left bundle branch block (LBBB) was present during sinus rhythm in group A (n = 17), whereas LBBB was induced by permanent RV apical pacing in group B (n = 15). Following coronary sinus (CS) cannulation, a coil tip 0.014-in. guidewire was introduced into all available CS branches as a mapping electrode. Each patient's unipolar activation map was successfully constructed within 10 min, using the onset of surface QRS as reference. RESULTS: LV activation patterns were complex and varied in both groups. Earliest activation was usually apical, but latest activation was more heterogenous. The lateral or posterolateral branches were the sites of latest activation in 47% of group A and 73% of group B. An LV lead positioned conventionally by a physician blinded to the mapping data was concordant with the latest activated segment in 18% of group A and none of group B patients. CONCLUSIONS: Electroanatomic mapping of the CS tributaries is feasible and clinically practicable. Mapping revealed heterogenous conduction patterns that vary between patients in each group and between groups. An LV lead empirically placed in a lateral branch rarely paces the optimal, latest activated vein segment.

Cardiac resynchronization therapy in patients with challenging anatomy due to venous anomalies or adult congenital heart disease.

BACKGROUND: Cardiac resynchronization therapy (CRT) has proven salutary effects in patients with congestive heart failure, systolic dysfunction, and electromechanical dyssynchrony in the setting of ischemic, nonischemic, and congenital cardiomyopathy. While CRT device implants have become routine in the adult ischemic or nonischemic cardiomyopathy populations, patients with congenital heart disease offer special challenges due to unusual anatomic variations. METHODS: A comprehensive assessment of anatomic abnormalities is essential prior to implant. In addition, implant techniques and equipment must be tailored to the expected anatomy. A flexible approach is necessary-implant may require equipment and techniques adapted from vascular intervention. CONCLUSION: This article describes our approach to CRT implant in patients with congenital heart disease, and is illustrated by reports of several cases.

Polymorphic ventricular tachycardia--part II: the channelopathies.

In this article, we explore the clinical and cellular phenomena of primary electrical diseases of the heart, that is, conditions purely related to ion channel dysfunction and not structural heart disease or reversible acquired causes. This growing classification of conditions, once considered together as "idiopathic ventricular fibrillation," continues to evolve and segregate into diseases that are phenotypically, molecularly, and genetically unique.

Polymorphic ventricular tachycardia-part I: structural heart disease and acquired causes.

Polymorphic ventricular tachycardia (PMVT) is an unusual ventricular tachyarrhythmia. Perhaps its most unique characteristic is a continuously evolving QRS morphology. Although the most common substrate for PMVT is structural heart disease, the prevalence of sudden cardiac death in the population without structural heart disease is even greater, and the absence of a myocardial substrate would suggest that PMVT is the anticipated cause of sudden cardiac death in this population as well. Mechanistically, PMVT is distinct from ventricular fibrillation. It appears to be a condition of abnormal repolarization and resultant cellular heterogeneities, and the principles of triggering and reentry have been demonstrated to govern its initiation and maintenance. The "channelopathies"-a growing category of inherited or acquired conditions that predispose to PMVT and sudden cardiac death-present a fascinating challenge with potentially dire consequences as there are few indicators of their existence except for subtle, if any, electrocardiographic changes. The ever-expanding number of pharmaceuticals that affect ion channel function further magnifies this risk.

Left Atrial Anatomy in Patients Undergoing Ablation for Atrial Fibrillation.

Background: Left atrial anatomy is highly variable, asymmetric, irregular and three-dimensionally unique. This variability can affect the outcome of atrial ablation. A catalog of anatomic varieties may aid patient selection and ablation approach and provide better tools for left atrial ablation. Methods: We analyzed computed tomography scans from 514 patients undergoing left atrial ablation. Images were processed on Advantage Windows with CardEP™ software (GE Healthcare, Waukesha, WI). Measurements of pulmonary vein (PV) ostial size along the long and short axes were made using double oblique cuts, and area of the ostia was calculated. Results: Patients with 2 left (LPV) and 2 right PVs (RPV) (62.6%), 2 LPVs and 3 RPVs (17.3%) and 1 LPV and 2 RPVs (14.2%) made up the three most common variants. In the 2-LPV/2-RPV anatomy, the ostial size and area of the RPVs were larger than their corresponding LPVs (p<0.001), and the ostial size and area of the superior PVs were larger than their corresponding inferior PVs (p<0.001). In the 2-LPV/3-RPV anatomy, the total area of the RPVs was larger than the total area of the LPVs (p<0.001). In the 1-LPV/2-RPV anatomy, the ostial size of the left common PV was larger than either right PV (p<0.007). However, the total area of the RPVs was larger than the area of the left common PV (p<0.002). The left common PV was also larger than any of the left veins in any of the other anatomies. The total PV area between the three most common anatomies was not significantly different. Conclusions: More than 37% of patients have a left atrial anatomy other than 2 left and 2 right PVs. This data may help in designing approaches for left atrial ablation, tailoring the procedure to individual patients and improving ablation tools.

Feasibility of early discharge after implantable cardioverter-defibrillator procedures.

INTRODUCTION: Registry data demonstrate considerably low complication rates after implantable cardioverter-defibrillator (ICD) procedures for primary prevention of sudden death. Yet standard of care includes postimplant overnight in-hospital observation that may levy substantial unnecessary financial burden on health care systems. In appropriate patients, discharge soon after implant could translate into significant cost savings, if such practice does not result in complications. We applied a simple clinical algorithm to assess feasibility of discharge on the same day of ICD implantation in patients at low risk for procedural complications. METHODS: We prospectively randomized primary prevention ICD candidates at low risk for complications (not pacing-dependent or requiring bridging heparin anticoagulation) to next-day discharge with overnight in-hospital observation, or same-day discharge with remote monitoring for 24 hours after ICD implant. Implants were performed via cephalic vein access, and randomization occurred after 4-hours clinical observation and device interrogation. All patients were followed for a minimum of 6 weeks to assess acute procedural complications. RESULTS: 71 patients comprised the study cohort (mean age 62, 79% male) after 3 were excluded. The most common indication for ICD implant was ischemic cardiomyopathy with ejection fraction ≤35%. Device data obtained through 24-hour remote monitoring was comparable to 4-hour postimplant parameters in same-day discharge patients. No acute complications occurred in same-day discharge patients; 1 next-day discharge patient developed pneumothorax. CONCLUSION: ICD implantation with same-day discharge is reasonable in patients at low risk for complications. Remote monitoring can be useful in indicating lead-parameter stability during the immediate postoperative period.

New echocardiographic techniques for evaluation of left atrial mechanics.

Until recently the left atrium had been subordinate to the left ventricle, but cardiologists now recognize that left atrial (LA) function is indispensable to normal circulatory performance. Transthoracic two-dimensional (2D) and Doppler echocardiography can elucidate parameters of LA function non-invasively. Yet, with the advent of 2D speckle-tracking echocardiography, we are able to detect early LA dysfunction even before structural changes occur. This is pivotal in some common disease states, such as atrial fibrillation, hypertension, and heart failure, in which LA deformation parameters can influence clinical management. However, a unique standardized technique to investigate LA deformation needs to be validated.

Cardiac Image Registration: Rotational Error Correction and Gated Stabilization for Cardiac Motion.

Background: Dynamic motion of the heart due to cardiac and respiratory cycles, and rotation from varying patient positions between imaging modalities, can cause errors during cardiac image registration. This study used phantom, patient and animal models to assess and correct these errors. Methods and Results: Rotational errors were identified and corrected using different phantom orientations. ECG-gated fluoro images were aligned with similarly gated CT images in 9 patients, and accuracy assessed during atrial fibrillation (AF) and sinus rhythm. A tracking algorithm corrected errors due to respiration; 4 independent observers compared 25 respiration sequences to an automated method. Following correction of these errors, target registration error was assessed. At 20 mm and 30 mm from the phantom model's center point with an in-plane rotation of 8 degrees, measured error was 2.94 mm and 5.60 mm, respectively, and the main error identified. A priori method accurately predicted ECG location in only 38% (p=0.0003) of 313 R-R intervals in AF. A posteriori method accurately gated the ECG during AF and sinus rhythm in 97% and 98% of 375 beats evaluated, respectively (p=NS). Tracking algorithm for ECG-gated motion compensation was identified as good or fair 96% of the time, with no difference between observers and automated method (chi-square=25; p=NS). Target registration error in phantom and animal models was 1.75±1.03 mm and 0 to 0.5 mm, respectively. Conclusions: Errors during cardiac image registration can be identified and corrected. Cardiac image stabilization can be achieved using ECG gating and respiration.