Giuseppe Pilato - Academia.edu (original) (raw)

Papers by Giuseppe Pilato

Research paper thumbnail of Cardioprotection beyond the guidelines: the SAFE trial results

European Heart Journal

ESC 2022 Guidelines suggest that low-risk patients receiving anthracyclines and/or anti-HER2 th... more ESC 2022 Guidelines suggest that low-risk patients receiving anthracyclines and/or anti-HER2 therapies can be followed within the oncology program with appropriate referral to cardio-oncology if cancer therapy-related cardiovascular toxicity or new or uncontrolled cardiovascular risks emerges. ACE-I or ARB and beta-blockers should not be considered for primary prevention. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at eight oncology departments in Italy. Between July 2015 and June 2020 patients with breast cancer were recruited and considered eligible for trial inclusion if they had indicated primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease or high-risk features were excluded. Cardioprotective therapy (bisoprolol (B), ramipril (R), or both drugs, as compared to placebo (P)) was administered for 1 year since t...

Research paper thumbnail of The right ventricle is not spared by the cardiotoxic effects of chemotherapy for breast cancer. Results of SAFE trial

European Heart Journal

Functional abnormalities of the right ventricle(RV) have been demonstrated in cancer patients r... more Functional abnormalities of the right ventricle(RV) have been demonstrated in cancer patients receiving anthracyclines and trastuzumab. AHA/ACC 2022 guidelines for heart failure recommend angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers for asymptomatic LV dysfunction. It would be important to determine whether these neurohormonal modulators are beneficial for the RV as well. Design The SAFE trial (NCT: 2236806) is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Patients with breast cancer were recruited between July 2015 and June 2020, and considered eligible if they had indicated primary or postoperative systemic chemotherapy with an anthracycline-based egimen. Patients with known cardiovascular disease or with high-risk features were excluded. Cardioprotective therapy [bisoprolol(B), Ramipril(R), or B+R], or placebo(P) were administered for 1 year since the initiation of chemotherapy or u...

Research paper thumbnail of Pharmacological cardioprotective strategy for non-metastatic patients affected by breast cancer receiving an anthracycline-based chemotherapy: Final results of the phase 3 SAFE trial

Journal of Clinical Oncology, Jun 1, 2023

Research paper thumbnail of Diastolic function is more sensitive than GLS in identifing cardiotoxicity. The SAFE trial results

European Heart Journal

Echocardiographic measures of diastolic dysfunction are associated with an increased risk of in... more Echocardiographic measures of diastolic dysfunction are associated with an increased risk of incident heart failure. Previous studies have shown that changes in diastolic function occur with anthracycline cancer therapy. However, they did not incorporate the newest classification of diastolic function nor evaluated the association with subsequent declines in systolic function. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Recruitment was conducted between July 2015 and June 2020. Patients with breast cancer were eligible if they had indication to primary or postoperative systemic therapy using an anthracycline-based regimen. Known cardiovascular disease or high-risk features were exclusion criteria. Cardioprotective therapy (bisoprolol(B), ramipril(R), or both drugs, as compared to placebo(P)) was administered for 1 year since chemotherapy initiation or until the end of trastuzumab therapy in the case of HE...

Research paper thumbnail of Cardioprotection in Anthracycline-Treated Breast Cancer Patients (SAFE): A Phase 3, Double-Blind, Placebo-Controlled, Multicentre Study

Research paper thumbnail of Cardiac Metastasis of Sacral Chordoma

The Annals of Thoracic Surgery

Chordoma is a rare tumor, usually diagnosed when the disease is advanced. Despite its slow growth... more Chordoma is a rare tumor, usually diagnosed when the disease is advanced. Despite its slow growth, it is locally aggressive with poor long-term prognosis. Surgery is the mainstay treatment. Although cardiac metastases are very rare, the heart is frequently involved in systemic neoplastic diseases. We describe a typical case of metastatic cordoma: age at first diagnosis, site of the primary tumor, slow growth of the cardiac metastasis were all typical features. Surgical excision of the mass from the right ventricular outflow tract is described together with echocardiographic, radiologic and histopathologic characteristics of the metastatic chordoma.

Research paper thumbnail of Patients with atrial fibrillation, 85 years or older treated with VKAs or DOACs

<p>Descriptive statistics of baseline features by treatment group.</p

Research paper thumbnail of Patients with atrial fibrillation, treatment-naive, 85 years or older

<p>Survival analysis—Cox proportional hazard model, hazard ratio and 95% confidence interva... more <p>Survival analysis—Cox proportional hazard model, hazard ratio and 95% confidence interval for major bleeding, stroke and death.</p

Research paper thumbnail of Events recorded during follow-up in patients 85 years or older with atrial fibrillation, treated with VKAs or DOACs, or DOACs treatment-naive

<p>Events recorded during follow-up in patients 85 years or older with atrial fibrillation,... more <p>Events recorded during follow-up in patients 85 years or older with atrial fibrillation, treated with VKAs or DOACs, or DOACs treatment-naive.</p

Research paper thumbnail of Surgical aortic valve replacement and left ventricular remodeling: Survival and sex‐related differences

Echocardiography, 2021

To analyze how left ventricular (LV) remodeling and hypertrophy geometry evolve after surgical ao... more To analyze how left ventricular (LV) remodeling and hypertrophy geometry evolve after surgical aortic valve replacement (SAVR) in octogenarian patients, and identify potential sex‐related differences and implications for long‐term outcomes.

Research paper thumbnail of 1029 Anthracycline and trastuzumab-induced subclinical cardiac damage and its prevention in the SAFE trial. Myocardial strain imaging and 3D echo interim analysis data

European Heart Journal - Cardiovascular Imaging, 2020

Background Benefit of anthracyclines and trastuzumab therapies on disease-free survival in breast... more Background Benefit of anthracyclines and trastuzumab therapies on disease-free survival in breast cancer is well known. Cardiotoxicity is a feared potential complication of both drugs. It usually progresses from cardiomyocyte injury to silent left ventricular dysfunction (LVD) which often becomes symptomatic and irreversible. Therefore, its prevention and early detection are of paramount importance in these cancer patients. Purpose SAFE trial (CT registry ID: NCT2236806) is a randomized phase 3, four-arm, single-blind, placebo-controlled study that aims to evaluate the effects of Bisoprolol (B) (5 mg, twice daily), Ramipril (R) (5 mg, twice daily) or the combination of the two (R + B), compared to placebo (P), on subclinical heart heart damage. Interim data of left ventricular function monitored with 3D Echo and Myocardial Strain Imaging are presented. Methods Out of 225 patients asked to participate, 191 were enrolled (mean age 48.9 ± 9.0 years). Follow-up monitoring (at 3, 6, 12 m...

Research paper thumbnail of Oral Anticoagulation in Very Elderly Patients with Atrial Fibrillation - A Nationwide Cohort Study

Circulation, Jan 28, 2018

BACKGROUND: Stroke prevention with oral anticoagulants (OACs) is the cornerstone for the manageme... more BACKGROUND: Stroke prevention with oral anticoagulants (OACs) is the cornerstone for the management of atrial fibrillation (AF). However, data about the use of OACs among patients ≥90 years of age are limited. We aimed to investigate the risk of ischemic stroke and intracranial hemorrhage (ICH) and the net clinical benefit of OAC treatment for very elderly patients with AF (≥90 years of age). METHODS: This study used the National Health Insurance Research Database in Taiwan. Risks of ischemic stroke and ICH were compared between 11 064 and 14 658 patients with and without AF ≥90 years of age without antithrombotic therapy from 1996 to 2011. Patients with AF (n=15 756) were divided into 3 groups (no treatment, antiplatelet agents, and warfarin), and the risks of stroke and ICH were analyzed. The risks of ischemic stroke and ICH were further compared between patients treated with warfarin and nonvitamin K antagonist OACs (NOACs) from 2012 to 2015 when NOACs were available in Taiwan. RESULTS: Compared with patients without AF, patients with AF had an increased risk of ischemic stroke (event number/patient number, incidence = 742/11 064, 5.75%/y versus 1399/14 658, 3.00%/y; hazard ratio, 1.93; 95% confidence interval, 1.74-2.14) and similar risk of ICH (131/11 064, 0.97%/y versus 206/14 658, 0.54%/y; hazard ratio, 0.85; 95% confidence interval, 0.66-1.09) in competing risk analysis for mortality. Among patients with AF, warfarin use was associated with a lower stroke risk (39/617, 3.83%/y versus 742/11 064, 5.75%/y; hazard ratio, 0.69; 95% confidence interval, 0.49-0.96 in a competing risk model), with no difference in ICH risk compared with nontreatment. When compared with no antithrombotic therapy or antiplatelet drugs, warfarin was associated with a positive net clinical benefit. These findings persisted in propensitymatched analyses. Compared with warfarin, NOACs were associated with a lower risk of ICH (4/978, 0.42%/y versus 19/768, 1.63%/y; hazard ratio, 0.32; 95% confidence interval, 0.10-0.97 in a competing risk model), with no difference in risk of ischemic stroke. CONCLUSIONS: Among patients with AF ≥90 years of age, warfarin was associated with a lower risk of ischemic stroke and positive net clinical benefit. Compared with warfarin, NOACs were associated with a lower risk of ICH. Thus, OACs may still be considered as thromboprophylaxis for elderly patients, with NOACs being the more favorable choice.

Research paper thumbnail of Papillary fibroelastoma of the right atrial appendage: Is it that rare?

Echocardiography, 2020

Any endocardial-lined surface may be the site of growth, left-heart valves being the most frequen... more Any endocardial-lined surface may be the site of growth, left-heart valves being the most frequent localization, mainly the aortic valve. Right atrial PFs were described in 18 cases. 3,4 In literature, only one case confirmed at histopathology 2 was described as having started in the right atrial appendage (RAA). In our routine 3-dimensional transesophageal echocardiography (3D-TEE) practice, we came across three cases of RAA PF that we present herein.

Research paper thumbnail of Cardioprotection beyond the guidelines: the SAFE trial results

European Heart Journal

ESC 2022 Guidelines suggest that low-risk patients receiving anthracyclines and/or anti-HER2 th... more ESC 2022 Guidelines suggest that low-risk patients receiving anthracyclines and/or anti-HER2 therapies can be followed within the oncology program with appropriate referral to cardio-oncology if cancer therapy-related cardiovascular toxicity or new or uncontrolled cardiovascular risks emerges. ACE-I or ARB and beta-blockers should not be considered for primary prevention. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at eight oncology departments in Italy. Between July 2015 and June 2020 patients with breast cancer were recruited and considered eligible for trial inclusion if they had indicated primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease or high-risk features were excluded. Cardioprotective therapy (bisoprolol (B), ramipril (R), or both drugs, as compared to placebo (P)) was administered for 1 year since t...

Research paper thumbnail of The right ventricle is not spared by the cardiotoxic effects of chemotherapy for breast cancer. Results of SAFE trial

European Heart Journal

Functional abnormalities of the right ventricle(RV) have been demonstrated in cancer patients r... more Functional abnormalities of the right ventricle(RV) have been demonstrated in cancer patients receiving anthracyclines and trastuzumab. AHA/ACC 2022 guidelines for heart failure recommend angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers for asymptomatic LV dysfunction. It would be important to determine whether these neurohormonal modulators are beneficial for the RV as well. Design The SAFE trial (NCT: 2236806) is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Patients with breast cancer were recruited between July 2015 and June 2020, and considered eligible if they had indicated primary or postoperative systemic chemotherapy with an anthracycline-based egimen. Patients with known cardiovascular disease or with high-risk features were excluded. Cardioprotective therapy [bisoprolol(B), Ramipril(R), or B+R], or placebo(P) were administered for 1 year since the initiation of chemotherapy or u...

Research paper thumbnail of Pharmacological cardioprotective strategy for non-metastatic patients affected by breast cancer receiving an anthracycline-based chemotherapy: Final results of the phase 3 SAFE trial

Journal of Clinical Oncology, Jun 1, 2023

Research paper thumbnail of Diastolic function is more sensitive than GLS in identifing cardiotoxicity. The SAFE trial results

European Heart Journal

Echocardiographic measures of diastolic dysfunction are associated with an increased risk of in... more Echocardiographic measures of diastolic dysfunction are associated with an increased risk of incident heart failure. Previous studies have shown that changes in diastolic function occur with anthracycline cancer therapy. However, they did not incorporate the newest classification of diastolic function nor evaluated the association with subsequent declines in systolic function. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Recruitment was conducted between July 2015 and June 2020. Patients with breast cancer were eligible if they had indication to primary or postoperative systemic therapy using an anthracycline-based regimen. Known cardiovascular disease or high-risk features were exclusion criteria. Cardioprotective therapy (bisoprolol(B), ramipril(R), or both drugs, as compared to placebo(P)) was administered for 1 year since chemotherapy initiation or until the end of trastuzumab therapy in the case of HE...

Research paper thumbnail of Cardioprotection in Anthracycline-Treated Breast Cancer Patients (SAFE): A Phase 3, Double-Blind, Placebo-Controlled, Multicentre Study

Research paper thumbnail of Cardiac Metastasis of Sacral Chordoma

The Annals of Thoracic Surgery

Chordoma is a rare tumor, usually diagnosed when the disease is advanced. Despite its slow growth... more Chordoma is a rare tumor, usually diagnosed when the disease is advanced. Despite its slow growth, it is locally aggressive with poor long-term prognosis. Surgery is the mainstay treatment. Although cardiac metastases are very rare, the heart is frequently involved in systemic neoplastic diseases. We describe a typical case of metastatic cordoma: age at first diagnosis, site of the primary tumor, slow growth of the cardiac metastasis were all typical features. Surgical excision of the mass from the right ventricular outflow tract is described together with echocardiographic, radiologic and histopathologic characteristics of the metastatic chordoma.

Research paper thumbnail of Patients with atrial fibrillation, 85 years or older treated with VKAs or DOACs

<p>Descriptive statistics of baseline features by treatment group.</p

Research paper thumbnail of Patients with atrial fibrillation, treatment-naive, 85 years or older

<p>Survival analysis—Cox proportional hazard model, hazard ratio and 95% confidence interva... more <p>Survival analysis—Cox proportional hazard model, hazard ratio and 95% confidence interval for major bleeding, stroke and death.</p

Research paper thumbnail of Events recorded during follow-up in patients 85 years or older with atrial fibrillation, treated with VKAs or DOACs, or DOACs treatment-naive

<p>Events recorded during follow-up in patients 85 years or older with atrial fibrillation,... more <p>Events recorded during follow-up in patients 85 years or older with atrial fibrillation, treated with VKAs or DOACs, or DOACs treatment-naive.</p

Research paper thumbnail of Surgical aortic valve replacement and left ventricular remodeling: Survival and sex‐related differences

Echocardiography, 2021

To analyze how left ventricular (LV) remodeling and hypertrophy geometry evolve after surgical ao... more To analyze how left ventricular (LV) remodeling and hypertrophy geometry evolve after surgical aortic valve replacement (SAVR) in octogenarian patients, and identify potential sex‐related differences and implications for long‐term outcomes.

Research paper thumbnail of 1029 Anthracycline and trastuzumab-induced subclinical cardiac damage and its prevention in the SAFE trial. Myocardial strain imaging and 3D echo interim analysis data

European Heart Journal - Cardiovascular Imaging, 2020

Background Benefit of anthracyclines and trastuzumab therapies on disease-free survival in breast... more Background Benefit of anthracyclines and trastuzumab therapies on disease-free survival in breast cancer is well known. Cardiotoxicity is a feared potential complication of both drugs. It usually progresses from cardiomyocyte injury to silent left ventricular dysfunction (LVD) which often becomes symptomatic and irreversible. Therefore, its prevention and early detection are of paramount importance in these cancer patients. Purpose SAFE trial (CT registry ID: NCT2236806) is a randomized phase 3, four-arm, single-blind, placebo-controlled study that aims to evaluate the effects of Bisoprolol (B) (5 mg, twice daily), Ramipril (R) (5 mg, twice daily) or the combination of the two (R + B), compared to placebo (P), on subclinical heart heart damage. Interim data of left ventricular function monitored with 3D Echo and Myocardial Strain Imaging are presented. Methods Out of 225 patients asked to participate, 191 were enrolled (mean age 48.9 ± 9.0 years). Follow-up monitoring (at 3, 6, 12 m...

Research paper thumbnail of Oral Anticoagulation in Very Elderly Patients with Atrial Fibrillation - A Nationwide Cohort Study

Circulation, Jan 28, 2018

BACKGROUND: Stroke prevention with oral anticoagulants (OACs) is the cornerstone for the manageme... more BACKGROUND: Stroke prevention with oral anticoagulants (OACs) is the cornerstone for the management of atrial fibrillation (AF). However, data about the use of OACs among patients ≥90 years of age are limited. We aimed to investigate the risk of ischemic stroke and intracranial hemorrhage (ICH) and the net clinical benefit of OAC treatment for very elderly patients with AF (≥90 years of age). METHODS: This study used the National Health Insurance Research Database in Taiwan. Risks of ischemic stroke and ICH were compared between 11 064 and 14 658 patients with and without AF ≥90 years of age without antithrombotic therapy from 1996 to 2011. Patients with AF (n=15 756) were divided into 3 groups (no treatment, antiplatelet agents, and warfarin), and the risks of stroke and ICH were analyzed. The risks of ischemic stroke and ICH were further compared between patients treated with warfarin and nonvitamin K antagonist OACs (NOACs) from 2012 to 2015 when NOACs were available in Taiwan. RESULTS: Compared with patients without AF, patients with AF had an increased risk of ischemic stroke (event number/patient number, incidence = 742/11 064, 5.75%/y versus 1399/14 658, 3.00%/y; hazard ratio, 1.93; 95% confidence interval, 1.74-2.14) and similar risk of ICH (131/11 064, 0.97%/y versus 206/14 658, 0.54%/y; hazard ratio, 0.85; 95% confidence interval, 0.66-1.09) in competing risk analysis for mortality. Among patients with AF, warfarin use was associated with a lower stroke risk (39/617, 3.83%/y versus 742/11 064, 5.75%/y; hazard ratio, 0.69; 95% confidence interval, 0.49-0.96 in a competing risk model), with no difference in ICH risk compared with nontreatment. When compared with no antithrombotic therapy or antiplatelet drugs, warfarin was associated with a positive net clinical benefit. These findings persisted in propensitymatched analyses. Compared with warfarin, NOACs were associated with a lower risk of ICH (4/978, 0.42%/y versus 19/768, 1.63%/y; hazard ratio, 0.32; 95% confidence interval, 0.10-0.97 in a competing risk model), with no difference in risk of ischemic stroke. CONCLUSIONS: Among patients with AF ≥90 years of age, warfarin was associated with a lower risk of ischemic stroke and positive net clinical benefit. Compared with warfarin, NOACs were associated with a lower risk of ICH. Thus, OACs may still be considered as thromboprophylaxis for elderly patients, with NOACs being the more favorable choice.

Research paper thumbnail of Papillary fibroelastoma of the right atrial appendage: Is it that rare?

Echocardiography, 2020

Any endocardial-lined surface may be the site of growth, left-heart valves being the most frequen... more Any endocardial-lined surface may be the site of growth, left-heart valves being the most frequent localization, mainly the aortic valve. Right atrial PFs were described in 18 cases. 3,4 In literature, only one case confirmed at histopathology 2 was described as having started in the right atrial appendage (RAA). In our routine 3-dimensional transesophageal echocardiography (3D-TEE) practice, we came across three cases of RAA PF that we present herein.