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La terapia di resincronizzazione
ed il trapianto in pazienti
Dr A. De Simone
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continue trastuzumab and in those in whom further therapy is withdrawn,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
Mortality in heart failure and reduced EF:
1 sudden death
2 acute decompensate heart failure or
cardiogenic shock
Terapia elettrica: la CRT
CRT migliora la mortalità e riduce il
numero di ricoveri
The MADIT Family of Clinical Trials
Continuing the legacy of landmark MADIT clinical trials in CRM
(196 patients)
(1232 patients)
(1820 patients)
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).
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 countries
Endpoint: 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)
Clinical Question:
Can prophylactic implantable
cardioverter defibrillator (ICD)
therapy dramatically improve
survival when compared to
conventional medical therapy
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)
Observation: HF
hospitalizations for more than
25% of the patients.
* Notes: “mild heart failure” refers to NYHA Class I and II HF patients; “high-risk” defined as EF ≤30%; QRS ≥130ms
MADIT-CRT – Inclusion Criteria
Ischemic Cardiomyopathy: NYHA I + II in the last three months
Non-ischemic Cardiomyopathy: NYHA II in the last three months
– 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 Storm
Eifling M. Texas Heart Institute Journal 2011;38:11-21
Efficacy of CRT
La CRT migliora l’emodinamica riducendo la
dissincronia ventricolare con conseguente
aumento di FE, di capacità funzionale e di
stabilizzazione dell’instabilità elettrica.
E’ inoltre possibile una soppressione del
meccanismo aritmico da CRT dovuto alla
preeccitazione dell’area di conduzione
lenta responsabile del rientro (Kowal RC HeartRhytm
Esc 2015
Dilated cardiomiopathy
Hypertrophic cardiomiopathy
Arrhytmogenic right ventricular cardiomiopathy
Infiltrative cardiomiopathy
Restrictive cardiomiopathy
Chagas desease cardiomiopathy
Left ventricular non compaction
Pediatric arrhytmsias and congenital desease
Inherited primary arrhythmia syndromes
Arrhytmias in normally structural hearts
Efficacy 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-induced
Rickard J1, 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 enddiastolic 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 press
Oliveira GH, JACC 2014; 63:240-248
Oliveira GH J Heart Lung trasplant 2012;31:805-810