Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy.

Chemotherapy-induced cardiomyopathy (CCMP) is a complication of chemotherapy treatment occurring in 9% of patients treated with the use of anthracyclines. Currently, risk stratification is based on clinical risk factors that do not adequately account for variable individual susceptibility. This suggests the presence of other determinants. In this case series, we describe 2 women with breast cancer who developed severe heart failure within months after chemotherapy. Genetic screening revealed truncating frameshift mutations in TTN, encoding the myofilament titin, in both women. To our knowledge, this is the 1st report of an association between truncating TTN variants and CCMP. Because truncations in TTN are the most common cause of familial and sporadic dilated cardiomyopathy, further research is needed to establish their prevalence in patients presenting with CCMP.

Multifocal spasm with acetylcholine in Prinzmetal angina.

A 60-year-old female patient with Prinzmetal angina and a single non-critical (<50%) focal obstruction in the right coronary artery was referred for percutaneous coronary intervention. Coronary angiography with provocative testing using incremental doses of acetylcholine demonstrated diffuse mild vasoconstriction and multifocal hyperreactive vasoconstriction in apparently normal coronary segments but not at the site of the nonsignificant obstruction. We refrained from intervention and advised avoidance of beta-blockade, and continuation of medical therapy with nitrates and calcium antagonists. (Neth Heart J 2008;16:134-6.).

[Congenital long QT-syndrome: the cause of recurrent syncope and sudden death at a young age]. / Congenitaal lange-QT-tijdsyndroom: oorzaak van recidiverende wegrakingen en plotse dood op jonge leeftijd.

Congenital long QT-syndrome (LQTS) was diagnosed in three patients. The first patient, a 10-year-old girl, presented with recurrent episodes of syncope during swimming and was diagnosed with type 1 LQTS. The second patient, a 36-year-old asymptomatic man, was accidentally diagnosed with type 2 LQTS. His family history revealed syncope and sudden death at a young age after auditory stimuli. Type 3 LQTS was diagnosed post-mortem in a 16-year-old boy who died during his sleep. All clinical diagnoses were confirmed by genetic testing. Congenital LQTS is one of the leading causes of sudden cardiac death at a young age. Mutations in genes encoding for myocardial ion channel proteins lead to a prolonged QT-interval and abnormal ST-T segments in the 12-lead ECG. Patients may present with syncope or sudden cardiac death caused by ventricular tachyarrhythmias. Genotype-specific differences in ECG-abnormalities and triggers for cardiac events may help to distinguish the type of LQTS and make possible the initiation of genotype-specific treatment before the results of genetic testing are known. Identification of the genetic substrate by genetic testing, genotype-specific treatment, and the possibility of treatment with an implantable cardioverter-defibrillator have all led to dramatic improvement in the prognosis of patients with LQTS. Therefore, young patients with unexplained recurrent syncope after specific stimuli and those with atypical forms of epilepsy should be referred for cardiologic evaluation in a specialised centre.

Not just any ICD device in patients with long-QT syndrome.

Patients with LQT syndrome are prone to lifethreatening arrhythmias. After surviving such an event, implantation of an ICD is indicated. There are, however, special subtle demands in the treatment of these patients. In this case report we describe our findings in a patient with LQT1 syndrome, and the pitfalls that can and must be avoided. (Neth Heart J 2007;15:418-21.).

Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery.

AIM: To assess the long-term cardioprotective effect of bisoprolol in a randomized high-risk population after successful major vascular surgery. High-risk patients were defined by the presence of one or more cardiac risk factor(s) and a dobutamine echocardiography test positive for ischaemia. METHODS: 1351 patients were screened prior to surgery, 846 patients had one or more risk factor(s), and 173 of these patients also had ischaemia during dobutamine echocardiography. One hundred and twelve patients could be randomized for additional bisoprolol therapy or standard care. Eleven patients died in the peri-operative period (up to 1 month after surgery). Randomized patients continued bisoprolol or standard care after surgery. During follow-up of 101 survivors (median 22 months, range 11-30) cardiac death or myocardial infarction was noted. No patient was lost during follow-up. Results The incidence of cardiac events during follow-up in the bisoprolol group was 12% vs 32% in the standard care group (P=0.025). Cardiac death occurred in 15 patients, nine patients in the standard care and in six in the bisoprolol group; myocardial infarction occurred in six patients, five in the standard care and one in the bisoprolol group. The odds ratio for cardiac death or myocardial infarction after surgery in high-risk patients with additional bisoprolol therapy was 0.30 (0.11-0.83). CONCLUSIONS: Bisoprolol significantly reduced long-term cardiac death and myocardial infarction in high-risk patients after successful major cardiac vascular surgery.

The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group.

BACKGROUND: Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery. METHODS: We performed a randomized, multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infarction within 30 days after major vascular surgery in patients at high risk for these events. High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography. Eligible patients were randomly assigned to receive standard perioperative care or standard care plus perioperative beta-blockade with bisoprolol. RESULTS: A total of 1351 patients were screened, and 846 were found to have one or more cardiac risk factors. Of these 846 patients, 173 had positive results on dobutamine echocardiography. Fifty-nine patients were randomly assigned to receive bisoprolol, and 53 to receive standard care. Fifty-three patients were excluded from randomization because they were already taking a beta-blocker, and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing. Two patients in the bisoprolol group died of cardiac causes (3.4 percent), as compared with nine patients in the standard-care group (17 percent, P=0.02). Nonfatal myocardial infarction occurred in nine patients given standard care only (17 percent) and in none of those given standard care plus bisoprolol (P<0.001). Thus, the primary study end point of death from cardiac causes or nonfatal myocardial infarction occurred in 2 patients in the bisoprolol group (3.4 percent) and 18 patients in the standard-care group (34 percent, P<0.001). CONCLUSIONS: Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction in high-risk patients who are undergoing major vascular surgery.