HEART and TIMI Scores Predict Severe Coronary Atherosclerosis in Patients With End-Stage Renal Disease.

Objectives History, EKG, age, risk factors, and troponin (HEART) and thrombolysis in myocardial infarction (TIMI) risk calculators have been validated to predict the risk of subsequent acute coronary syndromes and in some studies, severe coronary atherosclerosis in patients with a concerning clinical history. Their performance in patients with end-stage renal disease (ESRD), a population with a high pretest probability for the condition, is unknown. We aimed to determine whether HEART and TIMI scores can predict severe coronary atherosclerosis in patients with end-stage renal disease (ESRD). Methods A single-center retrospective cohort of admitted patients aged 18 years or older with ESRD on dialysis who underwent coronary angiography during admission (November 2010 to December 2017) was retrospectively reviewed. The outcome of coronary angiography was compared with the calculated HEART and TIMI scores at the time of presentation. Receiver operating characteristics and logistic regression models were used to determine optimal score cutoffs, score usefulness, and associations between outcomes, scores, and patient characteristics. Results Among 231 patient encounters, the mean HEART and TIMI scores were 6±2 and 3±1 points, respectively. Patients with diabetes mellitus, those 65 years old and older, and those reported to have angina pectoris were more likely to show severe coronary artery disease (CAD) lesions. Optimal score cutoffs for determining severe coronary lesions were between six and seven (area under the curve (AUC)=0.754, confidence interval (CI): 0.682-0.826) and between three and four (AUC=0.716, CI: 0.640-0.792) for the HEART and TIMI scores, respectively. Conclusion Similar to the general population, HEART and TIMI scores can predict severe coronary atherosclerosis in the complex ESRD population.

The Year in Cardio-oncology 2022.

Cardiovascular disease and cancer are the leading causes of death worldwide. With advent of novel and improved cancer therapies, a growing population of cancer patients with cardiac complications is seen. Taking this into consideration, the clinical studies have also shifted their focus from the study of a single disease to the interdisciplinary study of oncology and cardiology. This current review article provides a comprehensive review of all major articles and guidelines from the year 2021-2022 in the field of cardio-oncology.

Coronary Stent Healing in Cancer Patients-An Optical Coherence Tomography Perspective.

Objective: This study assessed stent healing patterns and cardiovascular outcomes by optical coherence tomography (OCT) in cancer patients after drug-eluting stent (DES) placement. Background: Cancer treatment, owing to its cytotoxic and antiproliferative effects, could delay stent healing and increase stent thrombosis risk, especially when dual antiplatelet therapy (DAPT) is discontinued early for oncological treatment. OCT can assess stent endothelialization and other healing parameters, which may provide clinical guidance in these challenging scenarios. Methods: This single-center retrospective study enrolled all cancer patients who underwent OCT for assessment of vascular healing patterns after prior DES placement from November 2009 to November 2018. Primary study endpoints were stent healing parameters, including stent coverage, apposition, degree of expansion, neointimal hyperplasia heterogeneity, in-stent restenosis, stent thrombosis, and overall survival (OS). Results: A total of 67 patients were included in this study. Mean time between DES placement and OCT evaluation was 154 ± 82 days. Stent healing matched published values for DES in non-cancer patients (P ≥ 0.063). At 1 year, the OS was 86% (95% confidence interval [CI]: 78-96%) with 0% incidence of acute coronary syndrome. Advanced cancers and active chemotherapies were associated with inferior OS (P = 0.024, hazard ratio [HR]: 3.50, 95% CI: 1.18-10.42 and P = 0.026, HR: 2.65, 95% CI: 1.13-6.22, respectively), while stent healing parameters were unassociated with OS. Forty-one patients (61%) had DAPT duration ≤6 months. Conclusions: Stent healing of contemporary DES appears similar in cancer and non-cancer patients. Cardiovascular risk of cancer patients after DES placement can be managed to facilitate timely cancer therapies, as the underlying malignancy and active chemotherapy ultimately determine survival.

Wells Score to Predict Pulmonary Embolism in Patients with Coronavirus Disease 2019.

BACKGROUND: The association between coronavirus disease 2019 (COVID-19) and hypercoagulability has been extensively described, and pulmonary embolism is a recognized complication of COVID-19. Currently, the need for computed tomography pulmonary angiogram (CTPA) relies on the Wells score and serum D-dimer levels. However, because COVID-19 patients have a different thrombotic and inflammatory milieu, the usefulness of the Wells score deserves further exploration for this patient population. We aimed to explore the ability of the Wells score to predict pulmonary embolism in patients with COVID-19. METHODS: In this retrospective study, patients found to have a CTPA and a COVID-19 diagnosis during the same admission were selected for analysis. Age and sex, CTPA results, and associated D-dimer levels were entered in a database. The Wells score sensitivity and specificity were calculated at different values, and the area under the curve of the receiver operating characteristic curve measured. RESULTS: Of 459 patients with COVID-19, 64 had a CTPA and 12 (19%) had evidence of pulmonary embolism. Previous or current evidence of deep vein thrombosis, a Wells score above 4 points, and serum D-dimer levels 5 times above age-adjusted upper normal values were associated with pulmonary embolism. However, only 33% of patients with pulmonary embolism had a Wells score of 4 points or higher. The area under the curve of the receiver operating characteristic showed non-discriminating values (0.54) CONCLUSIONS: Although a Wells score of 4 or more points predicted pulmonary embolism in our cohort, the outcome can be present even with lower scores.

Cancer treatment resumption in patients with new-generation drug-eluting stents.

OBJECTIVE: Percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DESs) may provide survival benefits to the cancer population undergoing PCI by expediting cancer treatment due to improved safety profile. We aimed to assess the safety of starting or resuming cancer treatment within 6 months of DES placement. We also compared the impact of different DES types on the overall survival (OS) in cancer patients and to identify a safe threshold for dual antiplatelet therapy (DAPT) discontinuation. METHODS: Cancer patients at our institution undergoing PCI with DES from December 2014 to June 2017 were included. Baseline demographics, DAPT duration, malignancy type, stage, and treatment were retrospectively analyzed. Univariate Cox regression was used to pinpoint baseline characteristics that correlated with OS. Survivorship was determined by Kaplan-Meier analysis, and the log-rank test was used to compare OS among DES types. RESULTS: Seventy-five patients were included. Of these, 45 had biodegradable polymer DES (Synergy) and 30 patients had durable polymer DES (Resolute Integrity, Xience, Ion, or Promus). Mean duration of follow-up was 1367 ± 334 days. There were two minor bleeding complications. No statistically significant differences in OS were found among different stent brands. Discontinuation of aspirin, early P2Y12 inhibitor discontinuation, and advanced cancer were significantly associated with OS. DAPT discontinuation <6 months after PCI was not associated with stent thrombosis or in-stent restenosis. There were two major adverse cardiac events: one in-stent restenosis while on DAPT for >12 months (attributed to radiation-induced heart disease) and one myocardial infarction and death. Of patients who resumed or started cancer treatment (chemotherapy, radiation therapy, or surgery) after PCI, all but one did so within 6 months of PCI, and most of them as early as 2 weeks. CONCLUSION: Patients may resume cancer treatment <6 months after PCI. We suggest that DAPT may be safely interrupted as early as 6 months, but additional longitudinal studies are needed.

Multi-parametric cell profiling with a CMOS quad-modality cellular interfacing array for label-free fully automated drug screening.

Cells are complex systems with concurrent multi-physical responses, and cell physiological signals are often encoded with spatiotemporal dynamics and further coupled with multiple cellular activities. However, most existing electronic sensors are only single-modality and cannot capture multi-parametric cellular responses. In this paper, a 1024-pixel CMOS quad-modality cellular interfacing array that enables multi-parametric cell profiling for drug development is presented. The quad-modality CMOS array features cellular impedance characterization, optical detection, extracellular potential recording, and biphasic current stimulation. The fibroblast transparency and surface adhesion are jointly monitored by cellular impedance and optical sensing modalities for comprehensive cell growth evaluation. Simultaneous current stimulation and opto-mechanical monitoring based on cardiomyocytes are demonstrated without any stimulation/sensing dead-zone. Furthermore, drug dose-dependent multi-parametric feature extractions in cardiomyocytes from their extracellular potentials and opto-mechanical signals are presented. The CMOS array demonstrates great potential for fully automated drug screening and drug safety assessments, which may substantially reduce the drug screening time and cost in future new drug development.

1024-Pixel CMOS Multimodality Joint Cellular Sensor/Stimulator Array for Real-Time Holistic Cellular Characterization and Cell-Based Drug Screening.

This paper presents a fully integrated CMOS multimodality joint sensor/stimulator array with 1024 pixels for real-time holistic cellular characterization and drug screening. The proposed system consists of four pixel groups and four parallel signal-conditioning blocks. Every pixel group contains 16 × 16 pixels, and each pixel includes one gold-plated electrode, four photodiodes, and in-pixel circuits, within a pixel footprint. Each pixel supports real-time extracellular potential recording, optical detection, charge-balanced biphasic current stimulation, and cellular impedance measurement for the same cellular sample. The proposed system is fabricated in a standard 130-nm CMOS process. Rat cardiomyocytes are successfully cultured on-chip. Measured high-resolution optical opacity images, extracellular potential recordings, biphasic current stimulations, and cellular impedance images demonstrate the unique advantages of the system for holistic cell characterization and drug screening. Furthermore, this paper demonstrates the use of optical detection on the on-chip cultured cardiomyocytes to real-time track their cyclic beating pattern and beating rate.

Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure.

BACKGROUND: The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of heart failure there is a switch from a predominance of fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but the inclusion of diabetic and nondiabetic patients obscures the distinction of adaptations to metabolic derangements from adaptations to heart failure per se. METHODS AND RESULTS: We performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in nondiabetic, lean, predominantly nonischemic, advanced heart failure patients at the time of heart transplantation or left ventricular assist device implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long-chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-coenzyme A (CoA) species incorporated into the Krebs cycle, whereas the myocardial concentration of acetyl-CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic ß-hydroxybutyryl-CoA, in association with increased myocardial utilization of ß-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl-CoA:3-oxoacid-CoA transferase, the rate-limiting enzyme for myocardial oxidation of ß-hydroxybutyrate and acetoacetate. CONCLUSIONS: These findings indicate increased ketone utilization in the severely failing human heart independent of diabetes mellitus, and they support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart.