Serum Biomarkers to Dynamically Predict the Risk of Cardiovascular Events in Patients under Oncologic Therapy. A Multicenter Observational Study.

Background: Serum biomarkers have been investigated as predictive risk factors for cancer-related cardiovascular (CV) risk, but their analysis is limited to their baseline level rather than their overtime change. Besides historically validated causal factors, inflammatory and oxidative stress (OS) related markers seem to be correlated to CV events but this association needs to be further explored. We conducted an observational study to determine the predictive role of the longitudinal changes of commonly used and OS-related biomarkers during the cancer treatment period. Methods: Patients undergoing anticancer therapies, either aged 75+ years old or younger with an increased CV risk according to European Society of Cardiology guidelines, were enrolled. We assessed the predictive value of biomarkers for the onset of CV events at baseline and during therapy using Cox model, Subpopulation Treatment-Effect Pattern Plot (STEPP) method and repeated measures analysis of longitudinal data. Results: From April 2018 to August 2021, 182 subjects were enrolled, of whom 168 were evaluable. Twenty-eight CV events were recorded after a median follow up of 9.2 months (Interquartile range, IQR: 5.1-14.7). Fibrinogen and troponin levels were independent risk factors for CV events. Specifically, patients with higher than the median levels of fibrinogen and troponin at baseline had higher risk compared with patients with values below the medians, hazard ratio (HR) = 3.95, 95% CI, 1.25-12.45 and HR = 2.48, 0.67-9.25, respectively. STEPP analysis applied to Cox model showed that cumulative event-free survival at 18 and 24 months worsened almost linearly as median values of fibrinogen increased. Repeated measure analysis showed an increase over time of D-Dimer (p-interaction event*time = 0.08), systolic (p = 0.07) and diastolic (p = 0.05) blood pressure and a decrease of left ventricular ejection fraction (p = 0.15) for subjects who experienced a CV event. Conclusions: Higher levels of fibrinogen and troponin at baseline and an increase over time of D-Dimer and blood pressure are associated to a higher risk of CV events in patients undergoing anticancer therapies. The role of OS in fibrinogen increase and the longitudinal monitoring of D-dimer and blood pressure levels should be further assessed.

Acute coronary syndromes do not promote prolonged in vivo FXII-dependent prothrombotic activity.

BACKGROUND: Coagulation FXII is activated on contact with lipoprotein particles. It has been suggested that contact with subendothelial tissue provides an alternative biological surface for FXII activation. Our aim was to investigate whether activated FXII (FXIIa) is elevated in patients with coronary atherosclerosis, and whether disease status (acute phase or stable state) affects circulating levels of FXIIa. METHODS: Circulating FXIIa levels were measured in the peripheral blood of 122 patients with coronary atherosclerosis (32, stable angina; 54, unstable angina; 36, nQ myocardial infarction) and in 45 age-matched subjects (Contr). RESULTS: FXIIa levels (median, first and third quartiles; ng/ml) were higher in patients than in Contr: 1.61 (1.26-2.02) vs. 1.34 (1.13-1.81) (p<0.01). FXIIa levels were similar among patients with stable angina [1.66 (1.23-1.91)], unstable angina [1.53 (1.21-2.04)], and nQ myocardial infarction [1.75 (1.34-2.03)]. The three groups of patients had similar prevalence for most atherothrombotic risk factors; patients with stable angina had an increased severity of coronary disease, which did not explain the different levels of FXIIa. Fasting levels of triglycerides were the best predictor of FXIIa levels in our patients. CONCLUSIONS: The finding of similar FXIIa levels among patients in either acute or chronic phases of coronary atherosclerosis suggests that the initial arterial denudation and the acute-phase response associated to acute coronary syndromes are not major determinants for prolonged FXII activation.

Usefulness of chronotropic incompetence to dipyridamole in predicting myocardial perfusion defects in heart transplant recipients.

The aim of this report was to assess the relation between heart rate response to dipyridamole infusion and perfusion defects at quantitative sestamibi single-photon emission computed tomographic imaging. We demonstrated in 166 heart transplant recipients that chronotropic incompetence to dipyridamole is the only significant and independent predictor of perfusion defects.

Risk of sudden death and outcome in patients with hypertrophic cardiomyopathy with benign presentation and without risk factors.

Patients with hypertrophic cardiomyopathy (HC) are reported to have a mortality rate of about 1.0% per year, and those patients without sudden death risk factors and with no or mild symptoms are generally considered to have a benign clinical presentation. However, the risk of sudden death and the outcome in this latter subgroup have not been investigated systematically and remain unresolved. We assessed the risk of sudden death and outcome in 653 consecutive patients with HC without risk factors and with no or mild symptoms. Over a median follow-up of 5.3 years, 35 patients (5.4%) died of HC-related causes. Mean age at death was 46 ± 20 years in patients who died suddenly and 66 ± 15 and 72 ± 9 years, respectively, in patients who died of heart failure or stroke. Event rate was 0.6% per year for sudden death, 0.2% per year for heart failure death, and 0.1% per year for stroke-related death. Sudden death risk was independently and inversely related to age, and risk of heart failure or stroke death was directly related to age (p = 0.020). At 10 years after the initial evaluation, sudden death risk was 5.9%, with sudden death rate being the lowest (0.3% per year) in patients with normal left atrial dimension (≤40 mm). In conclusion, in patients with HC without conventional risk factors and with no or mild symptoms, the risk of sudden death was not negligible, with an event rate of 0.6% per year. Heart failure and stroke-related death were less common and largely confined to older patients. These results underscore the need for a more accurate assessment of the sudden death risk in patients with HC.

Prevention of sudden cardiac death with implantable cardioverter-defibrillators in children and adolescents with hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to determine the efficacy of implantable cardioverter-defibrillators (ICDs) in children and adolescents with hypertrophic cardiomyopathy (HCM). BACKGROUND: HCM is the most common cause of sudden death in the young. The availability of ICDs over the past decade for HCM has demonstrated the potential for sudden death prevention, predominantly in adult patients. METHODS: A multicenter international registry of ICDs implanted (1987 to 2011) in 224 unrelated children and adolescents with HCM judged at high risk for sudden death was assembled. Patients received ICDs for primary (n = 188) or secondary (n = 36) prevention after undergoing evaluation at 22 referral and nonreferral institutions in the United States, Canada, Europe, and Australia. RESULTS: Defibrillators were activated appropriately to terminate ventricular tachycardia or ventricular fibrillation in 43 of 224 patients (19%) over a mean of 4.3 ± 3.3 years. ICD intervention rates were 4.5% per year overall, 14.0% per year for secondary prevention after cardiac arrest, and 3.1% per year for primary prevention on the basis of risk factors (5-year cumulative probability 17%). The mean time from implantation to first appropriate discharge was 2.9 ± 2.7 years (range to 8.6 years). The primary prevention discharge rate terminating ventricular tachycardia or ventricular fibrillation was the same in patients who underwent implantation for 1, 2, or ≥3 risk factors (12 of 88 [14%], 10 of 71 [14%], and 4 of 29 [14%], respectively, p = 1.00). Extreme left ventricular hypertrophy was the most common risk factor present (alone or in combination with other markers) in patients experiencing primary prevention interventions (17 of 26 [65%]). ICD-related complications, particularly inappropriate shocks and lead malfunction, occurred in 91 patients (41%) at 17 ± 5 years of age. CONCLUSIONS: In a high-risk pediatric HCM cohort, ICD interventions terminating life-threatening ventricular tachyarrhythmias were frequent. Extreme left ventricular hypertrophy was most frequently associated with appropriate interventions. The rate of device complications adds a measure of complexity to ICD decisions in this age group.

Myocardial lactate metabolism in relation to preoperative regional wall motion and to early functional recovery after coronary revascularization.

OBJECTIVE: To evaluate myocardial lactate metabolism as a marker of functional status after surgical coronary revascularization. DESIGN: Single-center, prospective, cohort study. SETTING: Tertiary care teaching hospital. PARTICIPANTS: Fifty patients with stable angina, ejection fraction >0.40, undergoing coronary artery bypass surgery for multiple-vessel disease. MEASUREMENTS AND MAIN RESULTS: Before (T1) and 30 minutes (T2) after coronary artery bypass grafting, the authors simultaneously sampled blood from artery and coronary sinus to determine myocardial lactate dynamics and performed transesophageal echocardiography (TEE) to assess segmental wall motion. Wall motion score index (WMSI) was calculated with an online/offline comparison. At T2, WMSI improved from 1.40 +/- 0.31 to 1.17 +/- 0.23 (p = 0.0001). Preoperatively, 2 patterns of lactate balance were found: 39 patients were lactate extractors (17% +/- 10%) and 11 were lactate producers (-11% +/- 11%). At T2, lactate metabolism was shifted towards a pattern opposite to the baseline: delta lactate extraction was -8% +/- 16% in extractors at T1 versus 7% +/- 9% in producers at T1 (p = 0.003). Changes in WMSI were not correlated with changes in lactate utilization. No single preoperative variable predicted postoperative WMSI or its changes from baseline. Cardiopulmonary bypass (CPB) time was the only significant predictor of postoperative lactate extraction by multivariate regression (r = -0.46, p = 0.001): at T2, patients in the highest CPB time quartile showed frank lactate production (-6% +/- 13%) when compared with those in the lowest quartile (15% +/- 11%, p = 0.005). However, postoperative WMSI was similar in different CPB time groups. CONCLUSIONS: Myocardial lactate metabolism pattern is not associated with functional status before and early after successful coronary revascularization. CPB time was the only significant predictor of postoperative lactate extraction. Measurement of lactate does not appear to be a valuable tool to assess the coupling of myocardial regional function and metabolism in the setting of coronary artery surgery and mild-to-moderate functional impairment.