Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.

Incidence of cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors.

BACKGROUND: The introduction of imatinib and tyrosine kinase inhibitors as therapeutic strategy for Philadelphia chromosome-positive chronic myeloid leukaemia (CML) has represented an important step forward for treatment of this disease. The aim of this study was therefore to evaluate the incidence of cardiovascular adverse events (CVEs) in patients affected by CML treated with TKI in an observational prospective study. METHODS: All consecutive patients affected by CML and treated with TKI in our Institution were enrolled in the study from February 2005 to September 2018 with a clinical, laboratory and instrumental follow-up. RESULTS: Sixty-one consecutive patients were enrolled, 29 with imatinib, 15 with nilotinib, 11 with dasatinib, 3 with bosutinib and 3 with ponatinib. Neither patients in therapy with bosutinib nor with nilotinib had CVE during follow-up. Incidence rates per person/year were 0 for bosutinib and nilotinib, 0.15 for dasatinib, 0.19 for imatinib and 1.69 for ponatinib (Log Rank p < 0.05); differences in terms of incidence of adverse outcomes remained significant also after multivariate correction. CONCLUSIONS: In patients with CML treated with TKIs, therapy with ponatinib was associated with a higher risk of CVE than other TKIs. The lowest incidence of CVE was associated with bosutinib and nilotinib.

Parachute mitral valve assessed by cardiac magnetic resonance.

Parachute mitral valve (PMV) is a congenital cardiac malformation where typically all tendons chordae converge and insert into one major papillary muscle. We report the case of 27-year-old man affected by Hodgkin's lymphoma-mixed cellularity subtype with polychemotherapy treatment and Barrett's esophagus who came to our attention for routine echocardiographic exam and evaluation of left ventricular function. In the presence of normal left ventricular systolic function and mild-moderate mitral regurgitation, a careful examination of mitral apparatus showed a single papillary muscle suspected for PMV. In the presence of Barrett's esophagus, the patient was further assessed cardiac magnetic resonance (CMR) that confirmed the diagnosis of PMV and excluded other associated congenital anomalies. Despite the rare incidence of PMV and a diagnosis generally based on transesophageal echocardiography, CMR could represent a useful tool, in selected cases, to confirm the diagnosis of PMV, identify other possible congenital anomalies, and assess ventricular and valvular function.

Anomalous Right Coronary Artery Origin from Left Main Stem: Role of Cardio-Computed Tomography in the Diagnosis and Therapeutic Approach.

Anomalous coronary arteries (ACAs) are rare but potentially life-threatening abnormalities of coronary circulation. Most of the variants are benign; however, some may lead to myocardial ischemia and/or sudden cardiac arrest. We report the case of a 75-year-old male complaining of exertion chest discomfort. Admission electrocardiogram on presentation showed sinus bradycardia with a slight elevation of ST-T in inferior leads. Troponin levels, however, were normal. Coronary angiography showed an anomalous right coronary artery (RCA) originating from the left main stem without significant stenosis. Cardio-CT confirmed the anomalous origin of the RCA from the left main stem and showed its anomalous course between the aorta and the pulmonary artery. The patient was deemed a candidate for surgery and transferred to a cardiac surgery center. Only the exact definition of the anatomic and clinical features of ACAs may allow the identification of the most appropriate and effective treatment. Multislice computed tomography may play a fundamental role in the diagnosis and treatment of ACAs.

Dual Coronary-Pulmonary Fistula Firstly Found at Routine Doppler Echocardiogram.

Congenital coronary-pulmonary fistulas (CPFs) are defined as an abnormal direct communication between one or more coronary arteries, with a cardiac or thoracic structure bypassing the capillary network. We report the case of a 73-year-old male, with a history of hypertension, asymptomatic for angina and dyspnea, who was referred for routine clinical control. Echocardiogram unexpectedly showed the presence of diastolic flow from the pulmonary trunk in parasternal short-axis view. Pulsed-wave Doppler confirmed the presence of diastolic flow and displayed the typical coronary flow pattern. Coronary angiography hence showed the presence of dual CPFs originating from the second segment of the left anterior descending coronary and the right coronary arteries. Careful routine Doppler echocardiograph examination may raise the suspicion of CPF in case of otherwise unexplained symptoms and may represent a simple, easy, repeatable tool for the first suspected diagnosis and follow-up of CPFs.

Tricuspid Papillary Fibroelastoma at Multimodal Imaging.

Papillary fibroelastoma is a rare benign cardiac tumor, second after cardiac myxoma as more frequent cardiac valvular tumor. The therapy is usually based on surgery according to size, mobility, symptoms, and risks of surgery. We report the case of a 67-year old female with transient ischemic attack. Echocardiography showed the presence of a round mobile formation localized on the atrial side of septal leaflets of tricuspid valve, first identified as an endocarditis vegetation. Cardiac magnetic resonance (cMRI) confirmed the presence of the mass and showed an isointense signal in T1-turbo spin echo sequences, hypointense in cine steady-state free precession and in first-pass sequences, and hyperintense in T2 and phase-sensitive inversion recovery with central hypointense core, with a suspected diagnosis of fibroelastoma. The patient underwent cardiac surgery and histology confirmed the presence of fibroelastic tissue with papillary extroflexions compatible with diagnosis of fibroelastoma. The use of cMRI may be useful in the evaluation of the exact position, dimensions, and nature of cardiac masses and fibroelastomas, diagnostic workup, and preliminary assessment before surgery.

Fast 'wandering' Takotsubo syndrome: atypical mixed evolution from apical to mid-ventricular ballooning.

We report the case of a 53-year-old woman admitted for typical chest pain and a diagnosis of Takotsubo syndrome (TTS). Initial echocardiographic presentation was characterized by apical and mid-ventricular akinesis and basal hyper-kinesis. Unexpectedly, later after admission, echocardiography showed recovered apical akinesis with an apparent 'migration' of systolic dysfunction to mid-ventricular segment and hyper-kinesis of apical and basal segments. One week after admission, left ventricular contractility completely recovered and cardiac magnetic resonance imaging did not show signs of subendocardial late-enhancement and myocardial edema. Cases of TTS may therefore occasionally rapidly 'wander' within left ventricular segments, raising doubts over the so far used classification of left ventricular patterns of ballooning in subjects with TTS (typical/atypical). Apparently, different patterns can rapidly evolve into each other. The absence of late-enhancement at cardiac magnetic resonance imaging could hypothetically identify rapidly 'wandering' cases.