ANMCO/AIOM/AICO Consensus Document on clinical and management pathways of cardio-oncology: executive summary.

Cardiovascular disease and cancer are leading causes of death. Both diseases share the same risk factors and, having the highest incidence and prevalence in the elderly, they often coexist in the same individual. Furthermore, the enhanced survival of cancer patients registered in the last decades and linked to early diagnosis and improvement of care, not infrequently exposes them to the appearance of ominous cardiovascular complications due to the deleterious effects of cancer treatment on the heart and circulatory system. The above considerations have led to the development of a new branch of clinical cardiology based on the principles of multidisciplinary collaboration between cardiologists and oncologists: Cardio-oncology, which aims to find solutions to the prevention, monitoring, diagnosis and treatment of heart damage induced by cancer care in order to pursue, in the individual patient, the best possible care for cancer while minimizing the risk of cardiac toxicity. In this consensus document we provide practical recommendations on how to assess, monitor, treat and supervise the candidate or patient treated with potentially cardiotoxic cancer therapy in order to treat cancer and protect the heart at all stages of the oncological disease. Cardiovascular diseases and cancer often share the same risk factors and can coexist in the same individual. Such possibility is amplified by the deleterious effects of cancer treatment on the heart. The above considerations have led to the development of a new branch of clinical cardiology, based on multidisciplinary collaboration between cardiologist and oncologist: the cardio-oncology. It aims to prevent, monitor, and treat heart damages induced by cancer therapies in order to achieve the most effective cancer treatment, while minimizing the risk of cardiac toxicity. In this paper, we provide practical recommendations on how to assess, monitor, treat and supervise patients treated with potential cardiotoxic cancer therapies.

[ANMCO/AICO/AIOM Consensus document: Clinical and management pathways in cardio-oncology]. / Documento di consenso ANMCO/AICO/AIOM: Snodi clinico-gestionali in ambito cardioncologico.

In Italy, cardiovascular diseases and cancer are the leading causes of death. Both diseases share the same risk factors and, having the highest incidence and prevalence in the elderly, they often coexist in the same individual. Furthermore, the enhanced survival of cancer patients registered in the last decades and linked to early diagnosis and improvement of care, not infrequently exposes them to the appearance of ominous cardiovascular complications due to the deleterious effects of cancer treatment on the heart and circulatory system. The above considerations have led to the development of a new branch of clinical cardiology based on the principles of multidisciplinary collaboration between cardiologists and oncologists: Cardio-oncology, which aims to find solutions to the prevention, monitoring, diagnosis and treatment of heart damage induced by cancer care in order to pursue, in the individual patient, the best possible care for cancer while minimizing the risk of cardiac toxicity. In this consensus document we provide practical recommendations on how to assess, monitor, treat and supervise the candidate or patient treated with potentially cardiotoxic cancer therapy in order to treat cancer and protect the heart at all stages of the oncological disease.

A giant coronary artery aneurysm with coronary arteriovenous fistula in asymptomatic elderly patient.

Coronary Arteriovenous Fistula (CAF) is a rare defect that occurs in 0.1-0.2% of patients undergoing coronary angiography; Coronary Artery Aneurism (CAA) also occurs in approximately 15-19% of patients with CAF. It is usually congenital, but in rare occasions it occurs after chest trauma, cardiac surgery, or coronary interventions. The case described is that of a 72-year-old woman, without previous history of cardiovascular disease, who presented a huge cardiac mass. A multimodal approach was necessary to diagnose a giant CAA with CAF responsible for compression and displacement of cardiac structures. Due to likely congenitally origin of the lesion and the absence of symptoms correlated to the CAA and to the CAF we decided to avoid invasive interventions and to treat the patient with medical therapy.

Role of renal function on the development of cardiotoxicity associated with trastuzumab-based adjuvant chemotherapy for early breast cancer.

Anthracyclines, taxanes and trastuzumab are used for therapy in early breast cancer (EBC) overexpressing Human Epidermal Growth Factor 2 (HER2+). These drugs, considered alone, do not present potential nephrotoxicity. However, renal dysfunction (RD) may increase the myocardial sensibility to the insult of these chemotherapies used in combination. The aim of the study is to assess the role of RD on the development of cardiotoxicity associated with trastuzumab-based adjuvant therapy (aTrastC) for EBC. Clinical and echocardiographic data of 499 women with ERB2+ EBC were analyzed. At 12-month evaluation, any symptoms of heart failure or decrease in left ventricular ejection fraction (LVEF) were recorded. Patients who had cardiotoxicity (n = 130, 26 %) were older (57 ± 11 vs. 55 ± 11 years; p = 0.03), had lower glomerular filtration rate (GFR) (76 ± 15 vs. 83 ± 19 ml/min/1.73 m(2); p = 0.003), higher LVEF (69 ± 6 vs. 63 ± 5 %; p < 0.001) and received more frequent doses of doxorubicin (18 vs. 9 %; p = 0.01) than those who did not. In patients with GFR 60-90 and <60 ml/min/1.73 m(2), the 1-year event rate of cardiotoxicity was 25 and 38 %, respectively. ROC analysis showed that the best cut-off point of GFR for predicting cardiotoxicity was 78 ml/min/1.73 m(2) (AUC = 0.66, [95 % CI 0.57-0.74]). Multiple logistic regression revealed that GRF <78 ml/min/1.73 m(2) was the strongest predictor of cardiotoxicity (OR 3.32 [CI = 1.30-8.65]), independent of doxorubicin treatment and left ventricular ejection fraction. A reduced renal function represents a condition of higher risk of developing cardiotoxicity at 12-month follow-up in patients with HER2 + EBC treated with aTrastC.

Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer.

BACKGROUND: Adjuvant trastuzumab therapy improves survival of human epidermal growth factor receptor 2 (HER2)-positive women with early breast cancer (EBC). A careful monitoring of cardiac function is needed due to potential trastuzumab cardiotoxicity (Tcardiotox). To date, the incidence, timing, and phenotype of patients with Tcardiotox in clinical practice are not well known. METHODS AND RESULTS: A total of 499 consecutive HER2-positive women (mean age 55 ± 11 years) with EBC treated with trastuzumab between January 2008 and June 2009 at 10 Italian institutions were followed for 1 year. We evaluated incidence, time of occurrence, and clinical features associated with Tcardiotox. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography at baseline and at 3, 6, 9, and 12 months during trastuzumab therapy. Tcardiotox was recognized in 133 patients (27%): 102 (20%) showed asymptomatic reduction in LVEF of >10% but ≤20% (grade 1 Tcardiotox); 15 (3%) had asymptomatic decline of LVEF of >20% or <50% (grade 2); and 16 (3%) had symptomatic heart failure (grade 3). Trastuzumab was discontinued due to cardiotoxicity in 24 patients (5%) and restarted in 13 after LVEF recovery. Forty-one percent of Tcardiotox cases occurred within the first 3 months of follow-up, most prevalently in older patients with higher creatinine levels and in patients pretreated with doxorubicin and radiotherapy. CONCLUSIONS: In clinical practice, Tcardiotox is frequent in HER2-positive women with EBC and occurs in the first 3 months of therapy. Cardiac dysfunction is mild and asymptomatic in the majority of patients. The interruption of treatment is a rare event which occurs, however, in a significantly higher percentage than reported in randomized clinical trials.

Clinical characteristics and outcome of left ventricular ballooning syndrome in a European population.

We assessed the clinical characteristics and determinants of the prognosis of patients with left ventricular ballooning syndrome (LVBS) in an European population. A total of 128 patients with LVBS (98% women, age 67 ± 11 years) were prospectively followed up for a median of 13 months. A trigger event was identifiable in 58% of the patients. Anterior ST-segment elevation was documented in 38% and negative T waves in 41% of the patients. Apical ballooning was present in 82% and midventricular ballooning in 18%. The initial LV ejection fraction was 41 ± 9%. In-hospital events included the death of 1 patient (0.8%), LV failure in 13 (10%), LV thrombi in 4 (3.1%), sustained ventricular or supraventricular tachyarrhythmias in 6 (4.7%) and asystole in 2 patients (1.6%). The extent of wall motion abnormalities (odds ratio 4.16, p = 0.012), dyspnea at presentation (odds ratio 3.42, p = 0.01), and treatment with nitrates (odds ratio 0.30, p = 0.015) were significant univariate predictors of in-hospital events. The recovery of regional wall motion abnormalities occurred within 1 month of the event in 73% of patients. During follow-up, events occurred in 7 (6%) of 121 patients, including noncardiac death in 1 (0.8%), recurrent LVBS in 2 (1.6%), heart failure in 1 (0.8%), and recurrent chest pain in 3 (2.5%). In conclusion, in a European population, LVBS was characterized by a significant rate of in-hospital events, mainly related to pump failure, and low short-term mortality. The extent of wall motion abnormalities was the best predictor of acute events. Contractile recovery occurred within 1 month in most patients. The long-term prognosis was good, with a recurrence rate of <2%/year.

Aortic valve re-implantation technique with Gelweave Valsalva prosthesis: safety, reproducibility and pitfalls of a geometric reconstruction.

BACKGROUND: To evaluate the safety, reproducibility and pitfalls of an aortic valve re-implantation (AVRei) technique. METHODS: From June 2005 to December 2008, 30 patients underwent aortic valve-sparing re-implantation with Gelweave Valsalva prosthesis. Mean age was 66 +/- 7 years (range 47-81). Mean aortic root diameter was 49 +/- 6 mm (range 37-70) and 12 patients had an aortic insufficiency more than 2+. All the patients were elective, except three who underwent surgery for type A aortic dissection. Two patients had Marfan syndrome and one had a bicuspid aortic valve. Isolated aortic root replacement was performed in 26 patients, whereas hemiarch extension was required in four. All the survivors underwent serial echocardiographic assessment for functional results and multi-detector computed tomography (MDCT) for aortic root morphology evaluation. RESULTS: There was one early death and one re-exploration for bleeding. Two patients suffered from a perioperative stroke and four required a pacemaker implantation because of a complete atrio-ventricular block. Mean follow-up was 12 +/- 10 months (range 1-42) with no late deaths, whereas freedom from reoperation was 100% and freedom from aortic insufficiency 2+ or more was 96.5%. MDCT aortic root reconstruction showed a pseudo-normalization of the neo-sinuses of Valsalva mimicking the human normal aortic root morphology. CONCLUSION: AVRei with Valsalva conduit is a well-tolerated procedure both in elective and emergency situations. In well-selected patients, good functional and clinical results can be achieved, regardless of the cause of the aortic root disease. Application of simple surgical manoeuvres allows durable clinical efficacy to be obtained without the risk of major complications.

[Mitral regurgitation and left ventricular dysfunction: pathophysiology and surgical therapy]. / L'insufficienza mitralica nella disfunzione ventricolare sinistra: aspetti fisiopatologici e terapia chirurgica.

Functional mitral regurgitation (FMR) is a distinctive valve disease in which the left ventricle is the "culprit" and the mitral valve is the "victim". It differentiates from organic regurgitation because the structure of the valve and subvalvar apparatus are not affected, hence abnormalities of the left ventricle are not the consequence but the cause of valve disease. It is at present well known that FMR conveys adverse prognosis in patients with left ventricular dysfunction, with a graded relationship between severity and reduced survival. Recent important advances in the understanding of pathophysiology of this complex valve disease have recognized that FMR results from changes in the geometry of the left ventricle, the mitral annulus and papillary muscles. Assessment of the degree of FMR, by Doppler echocardiography, has allowed to identify patients with adverse prognosis and predictors of death, drawing guidelines for therapy. Standard surgical restrictive annuloplasty represents the treatment of choice, although improvement in long-term survival had not been clearly demonstrated yet. New surgical and interventional therapies are currently under development. In this paper we reviewed the most important published literature, trying to define the mechanisms of regurgitation, diagnosis and therapeutic options, making an update of future perspectives for the treatment of FMR.

Importance of surgical timing on postoperative outcome in patients with native valve acute endocarditis.

BACKGROUND: The present study was undertaken to establish whether surgical outcome could be influenced by surgical timing in patients affected by native valve endocarditis (NVE). METHODS: From March 2002 to December 2004, 19 patients underwent surgical operation for NVE. Aortic valve replacement (AVR) was performed in ten patients (53%), mitral valve repair (MVRep) was performed in five patients (26%) and multivalvular procedures were performed in the remaining four patients (21%). In three patients (15.5%), emergency surgery was required for refractory congestive heart failure, urgent surgery was necessary in ten patients [in six patients (31%) for paravalvular abscess, in three patients (15.5%) for macrovegetations and in one patient (6%) for systemic embolism, respectively], five patients (26.3%) with isolated valve incompetence underwent elective surgery, whereas delayed surgery was reserved for one patient (6%) because of pre-operative embolic stroke. RESULTS: There were no surgical procedure, cardiac or infectious related deaths at 30 days in the entire group. One patient died from an intravenous overdose. Follow-up was 100% complete in the 18 hospital survivors and ranged from 4 to 37 months (mean 14.2 +/- 10 months). There were no late death, recurrence of endocarditis, or re-operation at follow-up. CONCLUSIONS: The surgical results for NVE are excellent if surgical timing criteria are correctly applied during the acute phase of the infectious process. Immediate surgical correction is required when rapid hemodynamic deterioration occurs whereas a more aggressive surgical approach appears to be advisable in the case of paravalvular abscess, macrovegetations or systemic embolism. Delayed surgery is recommended when pre-operative stroke develops.