Prevention of Cardiotoxicities With Traditional and Novel Chemotherapeutic Agents.

PURPOSE OF REVIEW: This review will discuss strategies to prevent cardiotoxicity associated with chemotherapeutics. Forty years ago, investigators identified dose-dependent cardiotoxicity related to anthracycline-based regimens. Over recent decades, the development of more selective, mechanism-based chemotherapeutics has been associated with both on-target and off-target adverse cardiovascular sequelae. RECENT FINDINGS: Strategies to prevent or attenuate cardiotoxicities include limitation of anthracycline dose, appropriate patient selection, referral/access to cardio-oncology programs, early recognition of cardiac side effects, active cardio-surveillance, cardio-protective medical therapy, treatment-specific concerns, and follow-up. The importance of accurate diagnosis of cardiotoxicity is important as false-positive testing may result in inappropriate holding or stopping potentially life-saving chemotherapy. Data to support use of cardio-protective medical therapy to prevent chemotherapy-related cardiotoxicity is modest at best, limited by marginal effect size, small patient numbers, and short follow-up. The rapid growth in cardio-oncology clinics may facilitate larger multi-center randomized controlled trials in this area.

Angiographic severity does not correlate with fractional flow reserve in heavily calcified coronary arteries.

OBJECTIVES: To determine the relationship between severity of stenosis and hemodynamic significance in calcified coronary arteries. BACKGROUND: Severity of stenosis is widely used to determine the need for revascularization but the effect of lesion calcification on hemodynamic significance is not well understood. METHODS: Two hundred consecutive patients undergoing fractional flow reserve (FFR) testing of an intermediate coronary lesion with a pressure wire and intravenous infusion of adenosine were studied. Coronary calcium was quantified based upon radiopacities at the site of the stenosis on cineangiography using the method of Mintz et al. (0 = none or mild calcium, 1 = moderate calcium, 2 = severe calcium). RESULTS: Mean age was 61 ± 11 years, 66% were males, 87.5% had hypertension, 44.5% had diabetes, and 20.5% were current smokers. The mean coronary stenosis by quantitative coronary angiography was 60 ± 12% and the mean FFR was 0.83 ± 0.08. There were 109, 45, and 46 patients classified as Calcium Score of 0, 1, or 2, respectively. Compared to those with no/mild or moderate calcification, patients with severe coronary calcium were older and more likely to have chronic kidney disease and pulmonary disease. The correlation between angiographic severity and FFR decreased as lesion calcification increased [calcium score = 0 (R2 = 0.25, P < 0.005); calcium score = 1 (R2 = 0.11, P < 0.005); calcium score = 2 (R2 = 0.02, P = 0.35)]. CONCLUSIONS: In patients with heavily calcified coronary lesions, there was no association between angiographic stenosis and hemodynamic significance and FFR is needed to determine hemodynamic significance of intermediate lesions. © 2016 Wiley Periodicals, Inc.

Renal Biomarkers in Heart Failure: Systematic Review and Meta-Analysis.

Background: Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the risk stratification and prognostication of heart failure (HF) patients. However, very few have been adopted clinically, owing to the lack of consistency. Objectives: The authors aimed to study the association between cystatin C, NGAL, and KIM-1 and outcomes, mortality, hospitalizations, and worsening renal function (WRF) in patients with acute and chronic HF. Methods: We included peer-reviewed English-language articles from PubMed and EMBASE published up to December 2021. We analyzed the above associations using random-effects meta-analysis. Publication bias was assessed using funnel plots. Results: Among 2,631 articles, 100 articles, including 45,428 patients, met the inclusion criteria. Top-tertile of serum cystatin C, when compared to the bottom-tertile, carried a higher pooled hazard ratio (pHR) for mortality (pHR: 1.59, 95% CI: 1.42-1.77) and for the composite outcome of mortality and HF hospitalizations (pHR: 1.49, 95% CI: 1.23-1.75). Top-tertile of serum NGAL had a higher hazard for mortality (pHR: 2.91, 95% CI: 1.49-5.67) and composite outcome (HR: 4.11, 95% CI: 2.69-6.30). Serum and urine NGAL were significantly associated with WRF, with pHRs of 2.40 (95% CI: 1.48-3.90) and 2.01 (95% CI: 1.21-3.35). Urine KIM-1 was significantly associated with WRF (pHR: 1.60, 95% CI: 1.24-2.07) but not with other outcomes. High heterogeneity was noted between studies without an obvious explanation based on meta-regression. Conclusions: Serum cystatin C and serum NGAL are independent predictors of adverse outcomes in HF. Serum and urine NGAL are important predictors of WRF in HF.

Negative Predictive Value and Prognostic Associations of Rb-82 PET/CT with Myocardial Blood Flow in CAV.

BACKGROUND: Invasive coronary angiography (ICA) is the traditional screening modality for cardiac allograft vasculopathy (CAV). Positron emission tomography/computed tomography (PET/CT) scan with myocardial blood flow (MBF) quantification has emerged as a potential noninvasive alternative. OBJECTIVES: The aim of the study was to validate the diagnostic and prognostic value of a previously published algorithm for diagnosing CAV via PET/CT scans with MBF in a larger population. The study also sought to assess the downstream use of ICA when using PET/CT scanning as a screening modality. METHODS: Patients with heart transplantation without prior revascularization who underwent PET/CT scans with MBF were identified retrospectively. The accuracy of the algorithm was assessed in patients who underwent PET/CT scanning within 1 year of ICA. The prognostic value was assessed via a composite outcome of heart failure hospitalization, myocardial infarction, retransplantation, and all-cause mortality. RESULTS: A total of 88 patients for the diagnostic portion and 401 patients for the prognostic portion were included. PET CAV 0 had high negative predictive value for moderate to severe CAV (97%) and PET CAV 2/3 had a high positive predictive value for moderate to severe CAV (68%) by ICA. The cohort was followed for a median of 1.2 (IQR: 1.0-1.8) years with 46 patients having an adverse event. The annualized event rates were 6.9%, 9.3%, and 30.8% for PET CAV 0, 1, and 2/3, respectively (P < 0.001). CONCLUSIONS: An algorithm using PET/CT scanning with MBF demonstrates high a negative predictive value for CAV. PET CAV 2/3 is associated with a higher risk of adverse events and need for revascularization. PET/CT scanning with MBF is a reasonable alternative to ICA for screening for CAV.

Cardiac Risk of Extreme Exercise.

Habitual moderate intensity exercise is a vital component of a healthy lifestyle. For most of the population, increasing exercise duration and intensity beyond current recommendations appears to impart additional cardiovascular benefits; however, recent data has raised the possibility of an inflection point after which additional exercise no longer imparts benefit and may even result in negative cardiovascular outcomes. Exercise at the extremes of human endurance places a large hemodynamic stress on the heart and results in occasionally profound cardiac remodeling in order to accommodate the huge increases in cardiac output demanded by such endeavors. These changes have the potential to become maladaptive and heighten the risk of various arrhythmias, influence the rate of coronary atherosclerosis, and alter the risk of sudden cardiac death. Herein, we will discuss the potential negative impact of extreme exercise on cardiovascular risk.

Patients discharged from the emergency department after referral for hospitalist admission.

OBJECTIVES: To describe the characteristics and outcomes of patients discharged from the emergency department (ED) by hospitalist physicians. STUDY DESIGN: Retrospective cohort study at a tertiary academic medical center. METHODS: We used consultation Current Procedural Technology codes to identify patients discharged from the ED after referral for hospitalist admission from April 2011 to April 2014. We report patient demographics and primary diagnoses. Main outcome measures included return to the ED, hospitalization, or mortality, all within 30 days. RESULTS: There were 710 discharges from the ED for 670 patients referred for hospitalist admission; 21.7% returned to the ED, 12.3% were hospitalized, and 0.4% died within 30 days. Chest pain was the most common diagnosis (38.2%); 18.1% of these patients returned to the ED within 30 days. Patients with the following 3 diagnoses returned to the ED most frequently: sickle cell disease (82.4%), alcohol-related diagnoses (43.5%), and abdominal pain (35.7%). In multivariate analysis, abdominal pain (odds ratio [OR], 3.2; P <.001) and alcohol dependence (OR, 3.1; P = .003) increased the odds of ED revisits, whereas syncope (OR, 0.23; P = .049) reduced the odds. Chest pain reduced the odds of hospitalization (OR, 0.37; P = .005). CONCLUSIONS: A majority of patients discharged from the ED after referral for hospitalist admission did not return to the ED within 30 days, and the 30-day hospitalization rate was low. Our data suggest that hospitalists can safely aid patients by reducing the costs and adverse outcomes associated with unnecessary hospitalization.