Amyloid transthyretin cardiac amyloidosis: diagnosis and management.

Introduction: Cardiac amyloidosis is a disorder caused by the accumulation of abnormal protein products, amyloid, in the myocardium which subsequently impairs normal heart function. Heart failure with preserved ejection fraction has been increasingly attributed to amyloidosis and the resultant restrictive cardiomyopathy it creates. Areas covered: Amyloid transthyretin (ATTR) is one of several identified amyloid products that have been pathologically implicated in cardiac amyloidosis through advanced diagnostics. Improvements in nuclear imaging techniques, particularly scintigraphy, have enabled non-invasive diagnosis where previously endomyocardial biopsy was the only option. Despite being considered a rare disease, it is likely that ATTR cardiac amyloidosis is an underdiagnosed condition which has been supported by autopsy findings in heart failure populations. This article will review ATTR cardiac amyloidosis to provide physicians with the tools they need to establish a definitive diagnosis when there is a clinical suspicion of amyloidosis and provide the most appropriate care. Expert commentary: Increased awareness and improved diagnostic techniques will lead to earlier diagnosis and a greater understanding of the clinical presentation. The anticipated increases in the prevalence of this disease due to increased clinical awareness will require, and in-part, facilitate the development of new therapies to manage this patient population.

Cardiovascular events in chronic myeloid leukemia clinical trials. Is it time to reassess and report the events according to cardiology guidelines?

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). Although these treatments have changed the natural course of CML and many other cancers, they may cause cardiovascular and/or metabolic complications. In this review, we discuss how overlooking the main drivers of cardiovascular events (CVEs) and lack of standard definitions for cardiovascular adverse events might have affected these event rates in CML trials. Methodological limitations that affect the available data are discussed, with an emphasis on the future direction of cardiovascular safety research in trials of investigational drugs in cancer treatment.

Cardiovascular toxicities of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: preventive strategies and cardiovascular surveillance.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment and outcomes of chronic myeloid leukemia (CML). Despite their significant impact on the management of CML, there is growing evidence that TKIs may cause cardiovascular and/or metabolic complications. In this review, we present the current evidence regarding the cardiovascular safety profiles of BCR-ABL TKIs. Methodological challenges of studies that reported the cardiovascular safety of TKIs are discussed. We also propose management strategies for cardiovascular surveillance and risk factor modification during treatment with these agents.

Cardiovascular Events After Exposure to Nilotinib in Chronic Myeloid Leukemia: Long-term Follow-up.

INTRODUCTION: Nilotinib is a highly effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML). However, reports of cardiovascular toxicities caused by nilotinib have recently raised critical concerns. The aim of the present study was to evaluate the incidence of cardiovascular events (CVEs) and frequency of asymptomatic peripheral arterial disease (PAD) after long-term exposure to nilotinib. PATIENTS AND METHODS: In the present retrospective cohort, we evaluated the incidence of CVEs in 63 CML patients treated with nilotinib. The results of Doppler ultrasound examination of the carotid and vertebral and lower extremity arteries with ankle-brachial index measurements were collected in asymptomatic patients. The clinical outcome was a composite endpoint of PAD, acute coronary events, stroke, heart failure, and cardiovascular death. RESULTS: Sixty-three patients with a median age of 60 years were followed up for a median duration of 63 months. After a median nilotinib exposure of 49.30 months (range, 7.00-117.95 months), for a total exposure of 178.7 patient-years, 6 patients (9%) had experienced the clinical outcome. Four patients (8%) had abnormal arterial leg Doppler ultrasound findings. No significant lesions were reported in carotid/vertebral artery ultrasound examinations. Together, hypertension and low-density lipoprotein cholesterol > 2 mmol/L significantly increased the risk of CVEs or abnormal ultrasound findings (odds ratio, 37.65; 95% confidence interval, 4.06-348.9). CONCLUSION: The incidence of CVEs and the frequency of asymptomatic PAD in this population was low, and CVEs were associated with cardiovascular risk factors. Aggressive risk factor modification and applying standard definitions for measuring cardiovascular outcomes might have contributed to the findings. Further prospective and adequately powered studies are needed to explore the effect of the cardiovascular risk profile on CVEs in CML patients taking nilotinib.

The Added Value of Exercise Variables in Heart Failure Prognosis.

INTRODUCTION: Diminished exercise capacity is a key symptom in heart failure (HF). Exercise predictors (peak VO2, VE/VCO2 slope, and oxygen uptake efficiency slope [OUES]) are prognostic markers but studied in isolation. We evaluated if these exercise variables offer additional prognostic value to clinical predictors in HF. METHODS AND RESULTS: This was a single-institution retrospective cohort study of 517 consecutive HF patients. We used Cox proportional hazards modeling to determine the additional prognostic value of exercise variables on mortality, HF hospital admissions, and a composite outcome of ventricular assistance device (VAD) implantation, heart transplantation (HT), and death. During a mean follow-up of 2.7 years, 52 deaths, 47 HTs, and 19 VAD implantations occurred. After adjusting for age, New York Heart Association functional class, ejection fraction, body mass index, creatinine, and B-type natriuretic peptide, peak VO2 (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.85-0.96), OUES (HR 0.92, 95% CI 0.87-0.97), and VE/VCO2 (HR 1.03, 95% CI 1.01-1.05) were independent predictors of the composite outcome. Similar discriminatory capacity existed between the exercise variables (c-statistics 0.77, 0.78, and 0.78, respectively). Only VE/VCO2 was an independent predictor of admissions (HR 1.04, 95% CI 1.01-1.07), and only peak VO2 was an independent predictor of mortality (HR 0.90, 95% CI 0.84-0.98). CONCLUSIONS: Peak VO2, OUES, and VE/VCO2 are independent predictors of HF prognosis over recognized clinical variables. However, no single exercise variable was superior.

Are endothelial progenitor cells a prognostic factor in patients with heart failure?

For the last two decades, endothelial progenitor cells (EPCs) have been proposed as a novel prognostic marker and potential therapeutic target in patients with cardiovascular diseases. EPCs are involved in the process of adult vasculogenesis and repair of dysfunctional endothelium. Endothelial dysfunction has been documented in the peripheral and coronary arteries of chronic heart failure (HF) patients, and has proved to be an independent predictor of morbidity and mortality in HF patients. This has led researchers to analyze the association of EPCs and disease severity in HF patients. In this paper, we review studies analyzing the prognostic role of EPCs in patients with HF. Through a systematic search, we identified 14 relevant studies. Only one study analyzed mortality as an outcome; the others evaluated the association between EPC levels and patients' characteristics. Overall, results were inconsistent and suggested that levels of EPCs may vary according to factors such as disease severity, underlying cause of cardiomyopathy and medical therapy.

[Progress in mechanical circulatory support]. / Avances en asistencias circulatorias mecánicas.

Mechanical circulatory support is an important aspect of the management of patients with severe heart failure. Such support improves survival when treatment with intravenous inotropes or vasodilators, intra-aortic balloon counterpulsation and mechanical ventilation has failed. Technological advances in ventricular assist devices have reduced the risk of postoperative complications. However, risk stratification prior to device implantation is essential for reducing complications over both the short and long term. As knowledge about cardiovascular disease and the range of mechanical devices available continue to develop, the challenge for clinicians will be to use clinical findings to select the device that is most likely to benefit the individual patient. This article describes the circulatory support devices currently available for use in patients, the indications for their use, their beneficial effects on ventricular function, and the advantages and disadvantages of each particular device.

Avances en asistencias circulatorias mecánicas / Progress in Mechanical Circulatory Support

Los dispositivos de asistencia circulatoria son una importante terapia en el manejo de los pacientes con insuficiencia cardiaca avanzada. Las asistencias mecánicas mejoran la sobrevida en los pacientes en quienes fracasa el tratamiento médico con inotrópicos o vasodilatadores intravenosos, el balón de contrapulsación aórtico y la asistencia respiratoria mecánica. El avance tecnológico en el área de las asistencias ventriculares mecánicas ha reducido los riesgos de complicaciones postoperatorias. La estratificación del riesgo previo al implante del dispositivo es esencial para reducir las complicaciones a corto y a largo plazo. Debido a la constante evolución tanto de las enfermedades cardiovasculares como de los distintos dispositivos mecánicos, el desafío para los clínicos consiste en traducir la evidencia clínica en una correcta selección del dispositivo, a fin de lograr beneficio para cada paciente en particular. Este trabajo describe los dispositivos de asistencia circulatoria actualmente disponibles para uso clínico, las indicaciones para su uso, los efectos favorables en la función ventricular y las ventajas y desventajas específicas de cada dispositivo en particular (AU)

Mechanical circulatory support is an important aspect of the management of patients with severe heart failure. Such support improves survival when treatment with intravenous inotropes or vasodilators, intra-aortic balloon counterpulsation and mechanical ventilation has failed. Technological advances in ventricular assist devices have reduced the risk of postoperative complications. However, risk stratification prior to device implantation is essential for reducing complications over both the short and long term. As knowledge about cardiovascular disease and the range of mechanical devices available continue to develop, the challenge for clinicians will be to use clinical findings to select the device that is most likely to benefit the individual patient. This article describes the circulatory support devices currently available for use in patients, the indications for their use, their beneficial effects on ventricular function, and the advantages and disadvantages of each particular device (AU)