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Potential genetic predisposition for anthracycline-associated cardiomyopathy in families with dilated cardiomyopathy.

Wasielewski M, van Spaendonck-Zwarts KY, Westerink ND, Jongbloed JD, Postma A, Gietema JA, van Tintelen JP, van den Berg MP - Open Heart (2014)

Bottom Line: Anthracyclines are successfully used in cancer treatment, but their use is limited by their cardiotoxic side effects.Selected patients with AACM/DCM families with possible AACM (n=21) were analysed for mutations in cardiomyopathy-associated genes and presymptomatic cardiological evaluation of first-degree relatives was performed.The MYH7 c.4125T>A (p.Tyr1375X) mutation was identified in one patient with AACM.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics , University Medical Center Groningen, University of Groningen , Groningen , T he Netherlands.

ABSTRACT

Objective: Anthracyclines are successfully used in cancer treatment, but their use is limited by their cardiotoxic side effects. Several risk factors for anthracycline-associated cardiomyopathy (AACM) are known, yet the occurrence of AACM in the absence of these known risk factors suggests that other factors must play a role. The purpose of this study was to evaluate whether a genetic predisposition for dilated cardiomyopathy (DCM) could be a potential risk factor for AACM.

Methods: A hospital-based registry of 162 DCM families and two hospital-based registries of patients with cancer treated with systemic cancer therapy (n>6000) were reviewed focusing on AACM. Selected patients with AACM/DCM families with possible AACM (n=21) were analysed for mutations in cardiomyopathy-associated genes and presymptomatic cardiological evaluation of first-degree relatives was performed.

Results: We identified five DCM families with AACM and one patient with AACM with a family member with a possible early sign of mild DCM. Pathogenic MYH7 mutations were identified in two of these six families. The MYH7 c.1633G>A (p.Asp545Asn) and c.2863G>A (p.Asp955Asn) mutations (one double mutant allele) were identified in a DCM family with AACM. The MYH7 c.4125T>A (p.Tyr1375X) mutation was identified in one patient with AACM.

Conclusions: This study further extends the hypothesis that a genetic predisposition to DCM could be a potential risk factor for AACM.

No MeSH data available.


Related in: MedlinePlus

Flow chart patient inclusion. Patients with AACM data were collected from the hospital-based registry of DCM families (cohort I) and two hospital-based registries of patients with cancer (adult- or childhood-onset) treated with systemic cancer therapy (cohort II-adult-onset patients and cohort III-childhood-onset patients). AACM, anthracycline-associated cardiomyopathy; DCM, dilated cardiomyopathy; FU, follow-up; LVEF, left ventricular ejection fraction; SF, shortening fraction; WMSI, wall motion score index.* Two patients from a previously published study.13 †Using the cut-off values of ≤450 mg/m2 for doxorubicin and ≤600 mg/m2 for epirubicin, we aimed to include patients who received at most the submaximal dose of anthracyclines.
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OPENHRT2014000116F1: Flow chart patient inclusion. Patients with AACM data were collected from the hospital-based registry of DCM families (cohort I) and two hospital-based registries of patients with cancer (adult- or childhood-onset) treated with systemic cancer therapy (cohort II-adult-onset patients and cohort III-childhood-onset patients). AACM, anthracycline-associated cardiomyopathy; DCM, dilated cardiomyopathy; FU, follow-up; LVEF, left ventricular ejection fraction; SF, shortening fraction; WMSI, wall motion score index.* Two patients from a previously published study.13 †Using the cut-off values of ≤450 mg/m2 for doxorubicin and ≤600 mg/m2 for epirubicin, we aimed to include patients who received at most the submaximal dose of anthracyclines.

Mentions: Patients with AACM were selected from our hospital-based registry of proven DCM families (cohort I14) and from two hospital-based registries of patients with cancer (adult or childhood onset) treated with systemic therapy (cohort II—adult onset patients, cohort III—childhood onset patients15). For the flow chart of patient inclusion, see figure 1. All participants seen at our cardiogenetics outpatient clinic underwent a counselling procedure and agreed to take part in our study. The institutional review committee approved the protocol.


Potential genetic predisposition for anthracycline-associated cardiomyopathy in families with dilated cardiomyopathy.

Wasielewski M, van Spaendonck-Zwarts KY, Westerink ND, Jongbloed JD, Postma A, Gietema JA, van Tintelen JP, van den Berg MP - Open Heart (2014)

Flow chart patient inclusion. Patients with AACM data were collected from the hospital-based registry of DCM families (cohort I) and two hospital-based registries of patients with cancer (adult- or childhood-onset) treated with systemic cancer therapy (cohort II-adult-onset patients and cohort III-childhood-onset patients). AACM, anthracycline-associated cardiomyopathy; DCM, dilated cardiomyopathy; FU, follow-up; LVEF, left ventricular ejection fraction; SF, shortening fraction; WMSI, wall motion score index.* Two patients from a previously published study.13 †Using the cut-off values of ≤450 mg/m2 for doxorubicin and ≤600 mg/m2 for epirubicin, we aimed to include patients who received at most the submaximal dose of anthracyclines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4195921&req=5

OPENHRT2014000116F1: Flow chart patient inclusion. Patients with AACM data were collected from the hospital-based registry of DCM families (cohort I) and two hospital-based registries of patients with cancer (adult- or childhood-onset) treated with systemic cancer therapy (cohort II-adult-onset patients and cohort III-childhood-onset patients). AACM, anthracycline-associated cardiomyopathy; DCM, dilated cardiomyopathy; FU, follow-up; LVEF, left ventricular ejection fraction; SF, shortening fraction; WMSI, wall motion score index.* Two patients from a previously published study.13 †Using the cut-off values of ≤450 mg/m2 for doxorubicin and ≤600 mg/m2 for epirubicin, we aimed to include patients who received at most the submaximal dose of anthracyclines.
Mentions: Patients with AACM were selected from our hospital-based registry of proven DCM families (cohort I14) and from two hospital-based registries of patients with cancer (adult or childhood onset) treated with systemic therapy (cohort II—adult onset patients, cohort III—childhood onset patients15). For the flow chart of patient inclusion, see figure 1. All participants seen at our cardiogenetics outpatient clinic underwent a counselling procedure and agreed to take part in our study. The institutional review committee approved the protocol.

Bottom Line: Anthracyclines are successfully used in cancer treatment, but their use is limited by their cardiotoxic side effects.Selected patients with AACM/DCM families with possible AACM (n=21) were analysed for mutations in cardiomyopathy-associated genes and presymptomatic cardiological evaluation of first-degree relatives was performed.The MYH7 c.4125T>A (p.Tyr1375X) mutation was identified in one patient with AACM.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics , University Medical Center Groningen, University of Groningen , Groningen , T he Netherlands.

ABSTRACT

Objective: Anthracyclines are successfully used in cancer treatment, but their use is limited by their cardiotoxic side effects. Several risk factors for anthracycline-associated cardiomyopathy (AACM) are known, yet the occurrence of AACM in the absence of these known risk factors suggests that other factors must play a role. The purpose of this study was to evaluate whether a genetic predisposition for dilated cardiomyopathy (DCM) could be a potential risk factor for AACM.

Methods: A hospital-based registry of 162 DCM families and two hospital-based registries of patients with cancer treated with systemic cancer therapy (n>6000) were reviewed focusing on AACM. Selected patients with AACM/DCM families with possible AACM (n=21) were analysed for mutations in cardiomyopathy-associated genes and presymptomatic cardiological evaluation of first-degree relatives was performed.

Results: We identified five DCM families with AACM and one patient with AACM with a family member with a possible early sign of mild DCM. Pathogenic MYH7 mutations were identified in two of these six families. The MYH7 c.1633G>A (p.Asp545Asn) and c.2863G>A (p.Asp955Asn) mutations (one double mutant allele) were identified in a DCM family with AACM. The MYH7 c.4125T>A (p.Tyr1375X) mutation was identified in one patient with AACM.

Conclusions: This study further extends the hypothesis that a genetic predisposition to DCM could be a potential risk factor for AACM.

No MeSH data available.


Related in: MedlinePlus