Variability of cardiac troponin levels in normal subjects and in patients with cardiovascular diseases: analytical considerations and clinical relevance.

In accordance with all the most recent international guidelines, the variation of circulating levels of cardiac troponins I and T, measured with high-sensitivity methods (hs-cTnI and hs-cTnT), should be used for the detection of acute myocardial injury. Recent experimental and clinical evidences have demonstrated that the evaluation of hs-cTnI and hs-cTnT variations is particularly relevant: a) for the differential diagnosis of Acute Coronary Syndromes (ACS) in patients admitted to the Emergency Department (ED); b) for the evaluation of cardiovascular risk in patients undergoing major cardiac or non-cardiac surgery, and in asymptomatic subjects of the general population aged >55 years and with co-morbidities; c) for the evaluation of cardiotoxicity caused by administration of some chemotherapy drugs in patients with malignant tumors. The aim of this document is to discuss the fundamental statistical and biological considerations on the intraindividual variability of hs-cTnI and hs-cTnT over time in the same individual. Firstly, it will be discussed in detail as the variations of circulating levels strictly depend not only on the analytical error of the method used but also on the intra-individual variability of the biomarker. Afterwards, the pathophysiological interpretation and the clinical relevance of the determination of the variability of the hs-cTnI and hs-cTnT values ​​ in patients with specific clinical conditions are discussed. Finally, the evaluation over time of the variation in circulating levels of hs-cTnI and hs-cTnT is proposed for a more accurate estimation of cardiovascular risk in asymptomatic subjects from the general population.

Report from the Cardio-Oncology Symposium at the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Annual Congress.

Overview of the meeting The Cardio-Oncology Symposium at the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Annual Meeting mainly focused on the diagnosis, management and prevention of cardiovascular toxicity of cancer drugs, in particular, cardiac dysfunction induced by anthracyclines. Although a variety of cardiac biomarkers and imaging modalities are available, there remains no consensus regarding their appropriate use to identify early and late cardiotoxicity and to guide preventive strategies. At the same time, the multitude of pharmacological trials, aimed at preventing cardiac damage through a neurohormonal blockade, provided conflicting results. Nevertheless, the advent of novel heart failure medications can change the decision-making of the cardio-oncologist. This symposium attempted to harmonize these issues.

Cardio-oncological management of patients.

Session III of the Second International Colloquium on Cardio-Oncology focused on the diagnosis, management, and prevention of cardiovascular toxicity of cancer drugs. With a large menu of biomarkers and imaging modalities available to the cardio oncologist, there continues to be no consensus regarding the best use of each modality alone and in combination and whether we can actually prevent early and late cardiotoxicity using these tests to guide a preventive strategy. It has become increasingly clear that early diagnosis and intervention leads to less late cardiotoxicity and fewer cardiac-related events. This can be accomplished by taking a thorough history and performing a goal directed physical examination coupled with use of biomarkers and imaging studies. This session attempted to provide rationale for a current and integrated approach to these issues.

Breast cancer therapy-associated cardiovascular disease.

Breast cancer treatments have evolved over the past decades, although several widely used treatments have adverse cardiac effects. Radiotherapy generally improves the survival of women with breast cancer, although its deleterious cardiovascular effects pose competing risks of morbidity and/or mortality. In the past, radiation-associated cardiovascular disease was a phenomenon considered to take more than a decade to manifest, but newer research suggests that this latency is much shorter. Knowledge of coronary anatomy relative to the distribution of the delivered radiation dose has improved over time, and as a result, techniques have enabled this risk to be decreased. Studies continue to be performed to better understand, prevent and mitigate against radiation-associated cardiovascular disease. Treatments such as anthracyclines, which are a mainstay of chemotherapy for breast cancer, and newer targeted agents such as trastuzumab both have established risks of cardiotoxicity, which can limit their effectiveness and result in increased morbidity and/or mortality. Interest in whether ß-blockers, statins and/or angiotensin-converting enzyme (ACE)-inhibitors might have therapeutic and/or preventative effects in these patients is currently increasing. This Review summarizes the incidence, risks and effects of treatment-induced cardiovascular disease in patients with breast cancer and describes strategies that might be used to minimize this risk.

N-terminal pro-B-type Natriuretic Peptides' Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds.

BACKGROUND: N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. METHODS: The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. RESULTS: The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. CONCLUSIONS: Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

Late cardiac effects of cancer treatment.

Cardiac toxicities from cancer therapy can become evident many years after treatment, and these late cardiac effects can have a profound impact on cancer survivors. There are a myriad of potential cardiovascular complications from cancer therapy, but these can be grouped into three main categories. First, vascular conditions including atherosclerosis, thrombosis, and hypertension predominate. Second, cardiac structural problems, especially valvular degeneration, can have a dramatic impact long term. Lastly, and most importantly, cardiac dysfunction and heart failure are potentially common late cardiac effects and can certainly be prevented or detected early during active cancer therapy to result in optimal outcomes. Future research on late cardiac effects in cancer survivors needs to include advanced cardiac imaging techniques, novel cardiac biomarkers, and genetic determinants of response to cancer treatment.