Update on Immunotherapy Cardiotoxicity: Checkpoint Inhibitors, CAR T, and Beyond.

OPINION STATEMENT: Immunotherapy is an innovative approach to cancer treatment that involves using the body's immune system to fight cancer. The landscape of immunotherapy is constantly evolving, as new therapies are developed and refined. Some of the most promising approaches in immunotherapy include immune checkpoint inhibitors (ICIs): these drugs target proteins on the surface of T-cells that inhibit their ability to attack cancer cells. By blocking these proteins, checkpoint inhibitors allow T-cells to recognize and destroy cancer cells more effectively. CAR T-cell therapy: this therapy involves genetically modifying a patient's own T-cells to recognize and attack cancer cells. CAR T-cell therapy exhibits favorable response in many patients with refractory hematological cancers with growing clinical trials in solid tumors. Immune system modulators: these drugs enhance the immune system's ability to fight cancer by stimulating the production of immune cells or inhibiting the activity of immune-suppressing cells. While immunotherapy has shown great promise in the treatment of cancer, it can also pose significant cardiac side effects. Some immunotherapy drugs like ICIs can cause myocarditis, which can lead to chest pain, shortness of breath, and heart failure. Other cardiac side effects of ICIs include arrhythmias, pericarditis, vasculitis, and accelerated atherosclerosis. It is important for patients receiving immunotherapy to be monitored closely for these side effects, as prompt treatment can help prevent serious complications. Patients should also report any symptoms to their healthcare providers right away, so that appropriate action can be taken. CAR T-cell therapy can also illicit an exaggerated immune response creating cytokine release syndrome (CRS) that may precipitate cardiovascular events: arrhythmias, myocardial infarction, and heart failure. Overall, while immune modulating therapy is a promising and expanding approach to cancer treatment, it is important to weigh the potential benefits against the risks and side effects, especially in patients with high risk for cardiovascular complications.

Complications Associated With Transesophageal Echocardiography in Transcatheter Structural Cardiac Interventions.

BACKGROUND: Transesophageal echocardiograms (TEEs) performed during transcatheter structural cardiac interventions may result in greater complications than those performed in the nonoperative setting or even those performed during cardiac surgery. However, there are limited data on complications associated with TEE during these procedures. We evaluated the prevalence of major complications among these patients in the United States. METHODS: A retrospective cohort study was conducted using an electronic health record database (TriNetX Research Network) from large academic medical centers across the United States for patients undergoing TEE during transcatheter structural interventions from January 2012 to January 2022. Using the American Society of Echocardiography-endorsed International Statistical Classification of Diseases and Related Health Problems Clinical Modifications (10th edition) codes, patients undergoing TEE during a transcatheter structural cardiac intervention, including transaortic, mitral or tricuspid valve repair, left atrial appendage occlusion, atrial septal defect closure, patent foramen ovale closure, and paravalvular leak repair, were identified. The primary outcome was major complications within 72 hours of the procedure (composite of bleeding and esophageal and upper respiratory tract injury). The secondary aim was the frequency of major complications, death, or cardiac arrest within 72 hours in patients who completed intraoperative TEE during surgical valve replacement. RESULTS: Among 12,043 adult patients (mean age, 74 years old; 42% female) undergoing TEE for transcatheter structural cardiac interventions, 429 (3.6%) patients had a major complication. Complication frequency was higher in patients on anticoagulation or antiplatelet therapy compared with those not on therapy (3.9% vs 0.5%; risk ratio [RR] = 8.09, P < .001). Compared with those patients <65 years of age, patients ≥65 years of age had a higher frequency of major complications (3.9% vs 2.2%; RR = 1.75, P < .001). Complication frequency was similar among male and female patients (3.5% vs 3.7%; RR = 0.96, P = .67). Among 28,848 patients who completed surgical valve replacement with TEE guidance, 728 (2.5%) experienced a major complication. CONCLUSIONS: This study found that more than 3% of patients undergoing TEE during transcatheter structural cardiac interventions have a major complication, which is more common among those on anticoagulant or antiplatelet therapy or who are elderly. With a shift of poor surgical candidates to less invasive percutaneous procedures, the future of TEE-guided procedures relies on comprehensive risk discussion and updating practices beyond conventional methods to minimize risk for TEE-related complications.

Innovations in Cardio-oncology Resulting from the COVID-19 Pandemic.

OPINION STATEMENT: The COVID pandemic has transformed our approach to patient care, research, and training in cardio-oncology. While the early phases of the COVID pandemic were exceptionally frightening, we now can reflect on the innovative changes that brought more effective and patient-centered care to our doorsteps: expansion of telemedicine, integration of digital health, wider adoption of cardiac biomarkers, consolidation, and coordination of cardio-oncology testing. Normally, it takes years for health care systems to adopt new technology or modify patient care pathways; however, COVID pushed healthcare providers and the health systems to change at warp speed. All of these innovations have improved our efficacy and provided a more "patient-centered" approach for our cardio-oncology patients. The changes we have made in cardio-oncology will likely remain well beyond the pandemic and continue to grow improving the cardiovascular care of oncology patients.

Stress testing and myocardial perfusion imaging for patients after recovery from severe COVID-19 infection requiring hospitalization: A single-center experience.

BACKGROUND: As the coronavirus pandemic progresses, patients that have recovered from COVID-19-related hospitalization require resumption of care for other medical issues. Thus far, the literature has not detailed the experience of stress testing in this patient population. METHODS: We retrospectively reviewed patients that recovered from COVID-19-related hospitalizations and underwent SPECT MPI studies at the University of Alabama at Birmingham Medical Center. RESULTS: 15 patients (median age 60 years, 67% male) were identified with COVID-19-related hospitalization and then underwent SPECT MPI imaging after recovery. During COVID-19-related hospitalization (median length of stay 8 days), patients received various COVID-19 therapies; 3 required mechanical ventilation. Stress tests (4 Exercise, 11 Pharmacologic) were performed 65 days (interquartile range 31-94 days) after the diagnosis of COVID-19. None of the patients experienced serious adverse events during or after stress testing. One patient required regadenoson reversal using aminophylline due to chest pain. CONCLUSION: Over time, more patients that recover from COVID-19 infection will require MPI testing for myocardial ischemia evaluation. Our study provides some information regarding performing stress testing in patients who have recently recovered from COVID-19 infections requiring hospitalization. Further studies are recommended to establish formal protocols for testing in this cohort.

Strategies to Prevent Cardiotoxicity.

OPINION STATEMENT: Cardiovascular disease is a leading cause of death among cancer survivors. While the field of cardiology as a whole is driven by evidence generated through robust clinical trials, data in cardio-oncology is limited to a relatively small number of prospective clinical trials with heterogeneous groups of cancer patients. In addition, many pharmaceutical trials in oncology are flawed from a cardiovascular perspective because they exclude patients with significant cardiovascular (CV) history and have wide variation in the definitions of CV events and cardiotoxicity. Ultimately, oncology trials often underrepresent the possibility of cardiovascular events in a "real world" population. Thus, the signal for CV toxicity from a cancer treatment is often not manifested until phase IV studies; where we are often caught trying to mitigate the CV effects rather than preventing them. Most of the data about cardiotoxicity from cancer therapy and cardioprotective strategies has been developed from our experience in using anthracyclines for over 50 years with dramatic improvement in cancer survivorship. However, as we are in an era where cancer drug discovery is moving at lightning pace with increasing survival rates, it is imperative to move beyond anthracyclines and commit to research on the cardiovascular side effects of all aspects of cancer therapy with a focus on prevention. We emphasize the role of pre-cancer treatment CV assessment to anticipate cardiac issues and ultimately optimizing CV risk prior to cancer therapy as an opportunity to mitigate cardiovascular risk from cancer therapy.

Collaborative cardiovascular management of patients with chronic myeloid leukemia on tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) of the BCR-ABL fusion protein have dramatically changed the mortality of chronic myeloid leukemia (CML) but they carry a risk of serious vascular morbidity. While TKIs do not cure CML, daily oral administration of a TKI can control CML and TKIs are chronic medications. Interestingly, vascular complications can occur at any time a patient is on a TKI. Therefore, it is imperative that all care team members and patients are aware of and watching for possible vascular complications. In the following review, a case of arterial thrombosis secondary to the TKI ponatinib is presented as well as a discussion of thrombotic and vascular adverse events reported with TKIs. TKIs are metabolized through the cytochrome P450 system and important drug interactions to consider are reviewed. Finally, we present a multidisciplinary approach to the management of patients with CML on TKIs.

Role of left ventricle deformation analysis in stress echocardiography for significant coronary artery disease detection: A diagnostic study meta-analysis.

BACKGROUND: We compared the diagnostic accuracy of longitudinal strain (LS) imaging during stress echocardiography with visual assessment of wall motion (WM) for detecting significant coronary artery disease (CAD). METHODS: Our systematic search included studies reporting diagnostic measures for LS imaging and visual assessment of WM for detecting significant CAD during stress echocardiography. Summary diagnostic accuracy measures including area under the curve (AUC), sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios (LRs) were estimated. RESULTS: In thirteen studies with 978 patients, ten studies used invasive coronary angiography as the reference standard. Pooled AUC for diagnosing significant CAD was 0.92 (95% confidence interval [CI] 0.89-0.94) for LS imaging as compared to 0.83 (95% CI 0.80-0.86), P < 0.001 for visual assessment of WM. LS imaging had higher sensitivity (88% [95% CI 84-92] vs 74% [95% CI 68-80], P < 0.001) and comparable specificity to visual assessment of WM (80% [95% CI 72-87] vs 83% [95% CI 74-90], P = 0.592). The DOR for LS imaging and visual assessment of WM was 31 and 15, P = 0.254, respectively. The positive LR was 4.5 for both; negative LR was 0.14 and 0.31, P = 0.002 for LS imaging and visual assessment of WM, respectively. CONCLUSIONS: Longitudinal strain imaging during stress echocardiography has better diagnostic accuracy for detecting significant CAD as compared to visual assessment of WM. Studies using larger sample size and standardized techniques of strain measurement are required to further ascertain the added advantage of strain measurement over visual assessment alone.

Predicting Outcomes in Patients With AsymptomaticModerate to Severe Aortic Stenosis.

Outcomes in asymptomatic patients with aortic stenosis (AS) have been reported primarily from tertiary centers. Whether observations from a community hospital cohort would be similar or if clinical variables would assume a more important role remains uncertain. This retrospective cohort study from one community hospital followed asymptomatic patients with moderate to severe AS for 3 years following an index echocardiogram. Patients underwent standard echocardiographic imaging and assessment of AS severity. Outcomes included aortic valve replacement, onset of Class 4 heart failure and cardiovascular death. Inclusion or exclusion criteria were met by 190 patients (body mass index of 30.8 ± 7.5 kg/m2 and age 70.9 ± 13.0 years). In this obese and racially diverse cohort, adverse outcomes occurred in 72 of 190 (38%), aortic valve replacement in 33 of 72 (46%), heart failure in 30 of 72 (42%), and cardiovascular death in 9 of 72 (13%). Univariate analyses found that the echocardiographic variables assessing AS severity (Vmax, mean aortic valve gradient, and the dimensionless index) were strongly associated with outcomes. A model predicting time to adverse outcomes included age, gender, Charlson index, Vmax, aortic valve area, the electrocardiographic variables of atrial fibrillation and left ventricular strain, and echocardiographic variables unrelated to the direct measurements of stenosis severity. In conclusion, direct echocardiographic measures of AS severity, echocardiographic parameters unrelated to AS severity plus the electrocardiographic variables of atrial fibrillation and left ventricular strain were the dominant predictors of adverse outcomes in a community hospital cohort of asymptomatic patients with moderate to severe AS.

Inflammatory bowel disease-related thoracic aortic thrombosis.

Arterial and venous thromboembolisms have long been associated with inflammatory bowel disease (IBD) and can cause significant morbidity and mortality. We present a patient with aortic arch thrombosis embolizing to the left lower extremity during hospitalization for active ulcerative colitis (UC). The limb was preserved following emergent embolectomy. Thrombophilia was attributed to UC, as hypercoagulable testing was negative. IBD is certainly a hypercoagulable state, and aggressive thromboembolism prevention should be considered for hospitalized patients with active disease.

Drug-eluting versus bare-metal stents for treating saphenous vein grafts.

BACKGROUND: Current data show conflicting results regarding safety and efficacy of drug-eluting stents (DES) versus bare-metal stents (BMS) for treating saphenous vein grafts (SVG). Our objective was to compare DES with BMS for SVG intervention. METHODS: Patients undergoing stenting with DES or BMS to SVG from January 2000 to June 2007 were included. To eliminate any unobserved bias regarding stent selection, the BMS cohort was divided into pre- and post-2003 when DES became available. Adjusted Cox analysis compared DES with pre- and post-2003 BMS patients. The primary end point was a composite of all-cause mortality, myocardial infarction, or target lesion revascularization. RESULTS: Of the total 566 patients, 217 (38%) received DES, 110 (20%) received BMS post-2003, and 239 (42%) received BMS pre-2003. Median follow-up was 2.9 years (interquartile range 1.4-4.9 years). There was a trend toward lower primary end point with DES compared to post-2003 BMS (91 events, adjusted hazard ratio 0.61, 95% CI 0.35-1.07, P = .08). However, despite 179 events, DES use was not associated with lower primary end point compared with pre-2003 BMS (adjusted hazard ratio 0.61, 95% CI 0.28-1.35, P = .23). CONCLUSIONS: Although DES showed a trend toward a lower primary end point when compared with BMS post-2003, this association was no longer present when DES was compared to pre-2003 BMS. These results are consistent with the preponderance of available data and indicate that unobserved bias in observational registries may explain the reported benefit of DES over BMS for treating SVG.