Fausto Pizzino

Multimodality Imaging in Cardiooncology

Cardiotoxicity represents a rising problem influencing prognosis and quality of life of chemotherapy-treated patients. Anthracyclines and trastuzumab are the drugs most commonly associated with development of a cardiotoxic effect. Heart failure, myocardial ischemia, hypertension, myocarditis, and thrombosis are typical manifestation of cardiotoxicity by chemotherapeutic agents. Diagnosis and monitoring of cardiac side-effects of cancer treatment is of paramount importance. Echocardiography and nuclear medicine methods are widely used in clinical practice and left ventricular ejection fraction is the most important parameter to asses myocardial damage secondary to chemotherapy. However, left ventricular ejection decrease is a delayed phenomenon, occurring after a long stage of silent myocardial damage that classic imaging methods are not able to detect. New imaging techniques including three-dimensional echocardiography, speckle tracking echocardiography, and cardiac magnetic resonance have demonstrated high sensitivity in detecting the earliest alteration of left ventricular function associated with future development of chemotherapy-induced cardiomyopathy. Early diagnosis of cardiac involvement in cancer patients can allow for timely and adequate treatment management and the introduction of cardioprotective strategies.

Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: cardiovascular magnetic resonance and nuclear cardiology.

Chemotherapy-induced cardiotoxicity (CTX) is a determining factor for the quality of life and mortality of patients administered potentially cardiotoxic drugs and in long-term cancer survivors. Therefore, prevention and early detection of CTX are highly desirable, as is the exploration of alternative therapeutic strategies and/or the proposal of potentially cardioprotective treatments. In recent years, cardiovascular imaging has acquired a pivotal role in this setting. Although echocardiography remains the diagnostic method most used to monitor cancer patients, the need for more reliable, reproducible and accurate detection of early chemotherapy-induced CTX has encouraged the introduction of second-line advanced imaging modalities, such as cardiac magnetic resonance (CMR) and nuclear techniques, into the clinical setting. This review of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to afford an overview of the most important findings from the literature about the role of CMR and nuclear techniques in the management of chemotherapy-treated patients, describe conventional and new parameters for detecting CTX from both diagnostic and prognostic perspectives and provide integrated insight into the role of CMR and nuclear techniques compared with other imaging tools and versus the positions of the most important international societies.

PFO: Button me up, but wait … Comprehensive evaluation of the patient

Patent foramen ovale (PFO) is a slit or tunnel-like communication in the atrial septum occurring in approximately 25% of the population. A wide number of pathological conditions have been linked to its presence, most notably, cryptogenic stroke (CS) and migraine. However, in the setting of a neurological event, it is not often clear whether the PFO is pathogenically related to the index event or an incidental finding. Therefore, a detailed analysis of several clues is needed for understanding PFOs clinical significance, with a frequent case-by-case decision about destination therapy. Indeed, the controversy about PFOs pathogenicity prompted a paradigm shift of research interest from medical therapy with antiplatelets or anticoagulants to percutaneous transcatheter closure, in secondary prevention. Observational data and meta-analysis of observational studies had previously suggested that PFO closure with a device was a safe procedure with a low recurrence rate of stroke. To date, however, recent randomized controlled trials have not shown the superiority of PFO closure over medical therapy. Thus, the optimal strategy for secondary prevention of paradoxical embolism in patients with a PFO remains unclear. Moreover, the latest guidelines for the prevention on stroke restricted indications for PFO closure to patients with deep vein thrombosis and high-risk of its recurrence. Given these recent data, in the present review, we critically discuss current treatment options, pointing out the role of a comprehensive patient evaluation in overcoming PFO closure restrictions and planning the best management for each patient.

Usefulness of late gadolinium enhancement MRI combined with stress imaging in predictive significant coronary stenosis in new-diagnosed left ventricular dysfunction.

BACKGROUND To evaluate the accuracy of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) and imaging stress test in predicting significant coronary artery disease (CAD) in left ventricular (LV) dysfunction. METHODS We enrolled 187 consecutive out-patients (61±17years) with new evidence of depressed (<45%) ejection fraction and no history of previous heart diseases and absence of Q-waves. All patients underwent coronary angiography (CA) and to LGE-CMR examination to identify ischemic and non-ischemic LGE. All patients underwent stress imaging to determine the presence of myocardial ischemia. RESULTS Ischemic-LGE was found in 83 patients and non-ischemic-LGE in 104. Significant CAD on CA was found in 86/187 patients. Ischemic-LGE showed a specificity of 94%, a sensitivity of 89% and an accuracy of 92% in identifying significant CAD. Imaging stress test was negative in 98/105 patients without CAD, and positive in 42/82 with significant CAD, showing a specificity of 93%, a sensitivity of 51% and an accuracy of 75% in identifying CAD. Combining CMR and stress test imaging, 94 patients had ischemic-LGE pattern and/or positive stress test for ischemia; of these 81/94 had significant CAD on CA and 13 had no CAD. Among the 93 patients with both tests negative, significant CAD was found in 5/93 patients. The combination of LGE and stress respect to only LGE did not improve the diagnostic accuracy (90 vs 92% respectively). CONCLUSION LGE-CMR had high accuracy in predicting significant CAD in ischemic LV dysfunction or as a bystander in non ischemic dysfunction.

Diagnosis of Chemotherapy-Induced Cardiotoxicity

Cardiotoxicity is a rising issue connected to use of chemotherapy and radiotherapy in the treatment of neoplastic diseases. Early diagnosis during follow-up is of paramount importance, and careful surveillance is recommended. Evaluation of left ventricular ejection fraction by echocardiography and nuclear medicine techniques is widely used in clinical practice; however, their sensitivity in detecting early cardiac damage is low. New instruments like speckle-tracking imaging, cardiac magnetic resonance and cardiac circulating biomarkers are available to clinicians to best evaluate the onset and progression of cardiotoxic effects, improving the therapeutic management and final outcome for the patient. (J Patient-Centered Res Rev. 2014;1:121-127.)

How arterial stiffness may affect coronary blood flow: a challenging pathophysiological link.

Aims A relationship between arterial stiffening and coronary flow abnormalities, although not fully elucidated, has been observed. The purpose of this study was to investigate the relationship among carotid stiffness, measured using echo-tracking, and Doppler parameters of coronary blood flow, sampled at the left anterior descending (LAD) artery. Methods We studied 88 consecutive patients (49 men, mean age 51.2 ± 16.2 years) with cardiovascular risk factors but without history of cardiovascular diseases. Each patient underwent echocardiographic evaluation for measurement of the diastolic velocity time integral (DVTI) and calculation of the diastolic velocity time integral coronary index (DVTICI), the ratio between DVTI and total velocity time integral of LAD artery flow × 100, and carotid ultrasound for measurement of carotid intima media thickness (IMT) and stiffness parameters such as &bgr; index and elastic modulus (Ep). Results DVTICI was significantly greater in men than in women (median 82, interquartile range 78–86 vs. median 80, interquartile range 73–83, respectively; P < 0.016). After correlating DVTICI with other variables, a significant inverse relation was obtained with &bgr; index (Rho = −0.449, P < 0.001), Ep (Rho = −0.478, P < 0.001), age (Rho = −0.52, P < 0.001), left ventricular mass index (Rho = −0.543, P < 0.001), E/E′ (Rho = −0.411, P < 0.001), pulse pressure (Rho = −0.417, P < 0.001) and IMT (Rho = −0.480, P < 0.001). With linear multiple regression analysis, only &bgr; index (P < 0.001), Ep (P < 0.001), male sex (P < 0.001) and left ventricular mass index (P = 0.008) were independently associated with reduction of DVTICI. Conclusion Increased arterial stiffness, directly affecting coronary perfusion, is associated with reduced diastolic coronary flow. Echo-tracking for feasible measurement of carotid artery stiffness parameters may be valuable in more accurate cardiovascular risk stratification.

High-risk patients with mild-moderate left ventricular dysfunction after a previous myocardial infarction. A long-term prognostic data by cardiac magnetic resonance

BACKGROUND Few studies have explored prognosis in patients with previous myocardial infarction (MI) with mild-moderate (MM) left ventricular (LV) dysfunction (D). The aim of our study was to investigate whether combining LV parameters obtained by cardiac magnetic resonance (CMR) improves risk stratification of patients with previous MI and MM-LV-D. METHODS In 418 consecutive patients (63.3±11.3years old, female 12.9%) with previous MI, we quantified LVEF, volumes and wall motion score index (WMSI) and measured the infarct extent by late gadolinium enhancement (LGE). According to LVEF, patients were considered with normal LVEF (>55%), MM-LV-D (LVEF>30 and ≤55%) and severe (S) LV-D (LVEF ≤30). RESULTS During follow-up (median, 39.7months) cardiac events (cardiac death or appropriate intra-cardiac defibrillator shocks) occurred in 17/99 of patients with S-LV-D, in 15/201 with MM-LV-D, and in only 1/118 of those with normal LV-EF. After adjustment for age, an extent of LGE >11.3%, a dilated LV (male >112ml/m2; female >92ml/m2) and a WMSI>1.59 were associated with adverse cardiac events in patients with MM-LV-D. In patients with MM-LV-D, when each of these 3 factors was observed, the prognosis was worse respect to those with 1-2 factors and no factor (p=0.035 and p=0.004, respectively). Prognosis was similar (p=0.61) between MM-LV-D patients with all 3 factors and those with S-LV-dysfunction. CONCLUSIONS A multiparametric CMR approach, which includes LGE, dilated LV and WMSI, permits to identify post MI patients with MM-LV-D with a risk of cardiac events similar to those with S-LV-D. Further multicenter studies are needed to confirm our data.

Isolated double orifice mitral valve in a young asymptomatic woman.

: Double orifice mitral valve (DOMV) is a rare congenital malformation of the mitral apparatus frequently associated with other congenital malformations of the heart, whereas the isolated form is rare. The prevalence is about 1% of congenital heart disease; valve stenosis and regurgitation are common findings. Echocardiography represents the best method to diagnose DOMV, providing both anatomical and functional data. We report a case of a young woman presenting with an isolated DOMV, in the absence of stenosis and significant regurgitation. The dysmorphic valve has been evaluated with both two-dimensional and three-dimensional echocardiography, providing impressive and detailed images of the peculiar anatomical configuration of the valve.

Congenital Gerbode Defect in a Patient With an Acute Myocardial Infarction and Cardiogenic Shock Masquerading as an Acute Ventricular Septal Defect.

EFT VENTRICLE-TO-RIGHT ATRIUM (LV-RA) shuntsare rare congenital or acquired defects of the membranousseptum described by Gerbode in 1958; their natural history canlead to enlargement of the right atrium and right ventriclefailure. Often the defects go unnoticed at birth, and diagnosis ismade in adulthood. The authors report a case of a 75-year-oldwoman with an acute myocardial infarction and cardiogenicshock for whom preoperative echocardiograms were readincorrectly as an infarct-related ventricular septal defect(IRVSD). The recognition of the pre-existing congenital LV-RA Gerbode malformation (GM) was made at the time ofsurgery for coronary revascularization, mitral and tricuspidannuloplasty, patent foramen ovale (PFO) closure, and ven-tricular septal defect (VSD) repair. The authors will review theimportant echocardiographic differences between the rare, pre-existing, congenital GM and the more common IRVSD.

Association between Anomalous Origin of the Left Main and Accessory Mitral Valve Tissue

A 73-year-old man presented to our department for ischemic alterations appeared during a stress electrocardiogram. The diagnostic process including coronary angiography, cardiac computed tomography and echocardiogram revealed an anomalous origin of the left main coronary artery from the commissural region between the left and the non-coronary Valsalva sinus associated with non-obstructive accessory mitral valve tissue. Although these malformations are relatively common the association is not described in literature to date.