Dr A. De SimoneDr A. De Simone

La terapia di resincronizzazione La terapia di resincronizzazione ed il trapianto in pazienti ed il trapianto in pazienti

oncologicioncologici

Breast. 2004 Jun;13(3):173-83. Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the

treatment of metastatic breast cancer. Suter TM1, Cook-Bruns N, Barton C Trastuzumab (Herceptin) is a humanised monoclonal antibody that

specifically targets HER2-positive breast cancer cells. Safety data collected from pivotal trials with trastuzumab indicate that this therapy is generally well tolerated. However trials of the combination of trastuzumab plus chemotherapy, and in particular chemotherapy with anthracyclines, have revealed an elevated incidence of cardiotoxicity in some patients, which was not apparent in preclinical or early clinical studies. Analyses of the available data suggest that in most cases the cardiotoxicity observed may reflect an exacerbation of anthracycline-induced cardiotoxicity. The biological mechanism of the cardiotoxicity has been investigated in several studies, and current data indicate that the heregulin/HER2-signalling pathway may have an important role. It is of note that the cardiotoxicity is generally reversible and can usually be managed with standard medical treatment. Improvement in cardiac function is seen both in patients who continue trastuzumab and in those in whom further therapy is withdrawn, indicating that with careful management anticancer therapy can be continued.

Mortality in heart failure and reduced EF: 1 sudden death

2 acute decompensate heart failure or cardiogenic shock

Terapia elettrica: la CRTTerapia elettrica: la CRT

CRT migliora la mortalitCRT migliora la mortalitàà e riduce e riduce il numero di ricoveriil numero di ricoveri

Continuing the legacy of landmark MADIT clinical trials in CRM

MADIT

(196 patients)

* Notes: “mild heart failure” refers to NYHA Class I and II HF patients; “high-risk” defined as EF ≤30%; QRS ≥130ms

MADIT II

(1232 patients)

MADIT-CRT

(1820 patients)

Clinical Question: Can prophylactic implantable cardioverter defibrillator (ICD) therapy dramatically improve survival when compared to conventional medical therapy alone? Size: 196 patients in the U.S.Endpoint: All-cause mortality.Key Finding: Use of ICDs resulted in a 54% reduction in the mortality rate in the defibrillator group as compared to the conventional medical therapy group. (p value: 0.009)

Clinical Question: Can heart attack survivors with impaired heart function (EF≤30%), and no other risk stratification, benefit from ICD therapy versus conventional therapy alone?Size: 1200 patients from 76 sites in the U.S.Endpoint: All-cause mortality.Key Finding: Use of ICDs resulted in a 31% reduction in the risk of death in heart attack survivors (p value: 0.016).Observation: HF hospitalizations for more than 25% of the patients.

Clinical Question:Does early intervention with CRT-D slow the progression of heart failure in high-risk patients* with mild heart failure* when compared to ICD-only therapy?Size: 1820 patients at 110 centers in 14 countriesEndpoint: All-cause mortality OR first heart failure event.Key finding: CRT-D therapy is associated with a significant 34% reduction in death or first HF event when compared to ICD therapy alone (p value: 0.001)

The MADIT Family of Clinical The MADIT Family of Clinical TrialsTrials

MADIT-CRT – Inclusion Criteria

Ischemic Cardiomyopathy: NYHA I + II in the last three months

or Non-ischemic Cardiomyopathy: NYHA II in the last three months

and

– LVEF ≤ 30%

– QRS-duration ≥ 130 ms (LBBB and RBBB)

– Optimal Pharmacologic Therapy: beta-blocker (> 3 months),ACE-Inhibitor or ATR-Blocker (> 1 month), diuretics

– Sinus rhythm at inclusion, PR < 250 ms

Moss AJ, Brown MW, Cannom DS, et al.. Ann Noninvasive Electrocardiol. 2005;10(4)(Suppl):34-43.

Electrical StormElectrical Storm

Eifling M. Texas Heart Institute Journal 2011;38:11-21

FV e TVFV e TV

Efficacy of CRTEfficacy of CRT

La CRT migliora l’emodinamica riducendo La CRT migliora l’emodinamica riducendo la dissincronia ventricolare con la dissincronia ventricolare con conseguente aumento di FE, di capacità conseguente aumento di FE, di capacità funzionale e di stabilizzazione funzionale e di stabilizzazione dell’instabilità elettrica.dell’instabilità elettrica.

E’ inoltre possibile una soppressione del E’ inoltre possibile una soppressione del meccanismo aritmico da CRT dovuto meccanismo aritmico da CRT dovuto alla preeccitazione dell’area di alla preeccitazione dell’area di conduzione lenta responsabile del conduzione lenta responsabile del rientro rientro (Kowal RC HeartRhytm 2004)(Kowal RC HeartRhytm 2004)

Esc 2015Esc 2015

Dilated cardiomiopathyHypertrophic cardiomiopathyArrhytmogenic right ventricular cardiomiopathyInfiltrative cardiomiopathyRestrictive cardiomiopathyChagas desease cardiomiopathyLeft ventricular non compactionPediatric arrhytmsias and congenital deseaseInherited primary arrhythmia syndromesArrhytmias in normally structural hearts

Efficacy of CRT in CCMPEfficacy of CRT in CCMP m J Cardiol. 2010 Feb 15;105(4):522-6. doi: 10.1016/j.amjcard.2009.10.024. Usefulness of cardiac resynchronization therapy in patients with Adriamycin-Usefulness of cardiac resynchronization therapy in patients with Adriamycin-

induced cardiomyopathy.induced cardiomyopathy. Rickard JRickard J11, Kumbhani DJ, Baranowski B, Martin DO, Tang WH, Wilkoff BL., Kumbhani DJ, Baranowski B, Martin DO, Tang WH, Wilkoff BL.

Adriamycin is a chemotherapeutic agent that can cause severe cardiotoxicity, which potentially carries a poorer long-term prognosis than other forms of cardiomyopathy. Cardiac resynchronization therapy (CRT) has been shown to improve quality of life, exercise capacity, left ventricular ejection fraction, and survival in selected patients with heart failure. It is unclear if patients with Adriamycin-induced cardiomyopathy (AIC) respond to CRT. We reviewed clinical and echocardiographic data on 18 consecutive patients with AIC who underwent implantation of a CRT device at the Cleveland Clinic from February 2000 to April 2007. Changes in clinical and echocardiographic parameters were compared to 189 consecutive patients with other forms of nonischemic cardiomyopathy (NIC) using similar end points. Patients with AIC demonstrated significant improvements in ejection fraction, left ventricular end-diastolic and end-systolic diameters, mitral regurgitation, and New York Heart Association functional class with CRT. These changes were similar to patients in the NIC cohort. In conclusion, patients with AIC may derive a significant echocardiographic and symptomatic benefit from CRT, which is similar to that seen in other forms of NIC.

Opreanu M. 2015 in pressOpreanu M. 2015 in press

Oliveira GH, JACC 2014; 63:240-248Oliveira GH, JACC 2014; 63:240-248

Oliveira GH J Heart Lung trasplant 2012;31:805-810Oliveira GH J Heart Lung trasplant 2012;31:805-810