No abstract

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.

Thoracic aortic aneurysms and dissections (TAAD) is a serious condition with high morbidity and mortality. It is estimated that 20% of non-syndromic TAAD cases are inherited in an autosomal-dominant pattern with variable expression and reduced penetrance. Mutations in myosin heavy chain 11 (MYH11), one of several identified TAAD genes, were shown to simultaneously cause TAAD and patent ductus arteriosus (PDA). We identified two large Dutch families with TAAD/PDA and detected two different novel heterozygote MYH11 variants in the probands. These variants, a heterozygote missense variant and a heterozygote in-frame deletion, were predicted to have damaging effects on protein structure and function. However, these novel alterations did not segregate with the TAAD/PDA in 3 out of 11 cases in family TAAD01 and in 2 out of 6 cases of family TAAD02. No mutation was detected in other known TAAD genes. Thus, it is expected that within these families other genetic factors contribute to the disease either by themselves or by interacting with the MYH11 variants. Such an oligogenic model for TAAD would explain the variable onset and progression of the disorder and its reduced penetrance in general. We conclude that in familial TAAD/PDA with an MYH11 variant in the index case caution should be exercised upon counseling family members. Specialized surveillance should still be offered to the non-carriers to prevent catastrophic aortic dissections or ruptures. Furthermore, our study underscores that segregation analysis remains very important in clinical genetics. Prediction programs and mutation evaluation algorithms need to be interpreted with caution.

Long-term beta-blocker use is associated with a reduction in the cardiac event rate, except for patients with 3 or more risk factors and positive findings on DSE.

Background-ENTIRE-TIMI 23 evaluated enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab. Methods and Results-Patients (nϭ483) with ST-elevation MI presenting Ͻ6 hours from symptom onset were randomized to full-dose TNK and either unfractionated heparin (UFH) (bolus 60 U/kg; infusion 12 U/kg per hour) or enoxaparin (1.0 mg/kg subcutaneously every 12 hoursϮinitial 30 mg intravenous bolus), or half-dose TNK plus abciximab and either UFH (bolus 40 U/kg; infusion 7 U/kg per hour) or enoxaparin (0.3 to 0.75 mg/kg subcutaneously every 12 hoursϮinitial intravenous bolus of 30 mg). With full-dose TNK and UFH, the rate of TIMI 3 flow at 60 minutes was 52% and was 48% to 51% with enoxaparin. Using combination therapy, the rate of TIMI 3 flow was 48% with UFH and 47% to 58% with enoxaparin. The rate of TIMI 3 flow among all UFH patients was 50% and was 51% among enoxaparin patients. Through 30 days, death/recurrent MI occurred in the full-dose TNK group in 15.9% of patients with UFH and 4.4% with enoxaparin (Pϭ0.005). In the combination therapy group, the rates were 6.5% with UFH and 5.5% with enoxaparin. The rate of major hemorrhage with full-dose TNK was 2.4% with UFH and 1.9% with enoxaparin; with combination therapy, it was 5.2% using UFH and 8.5% with enoxaparin. Conclusions-Enoxaparin is associated with similar TIMI 3 flow rates as UFH at an early time point while exhibiting advantages over UFH with respect to ischemic events through 30 days. These findings with enoxaparin are achieved with a similar risk of major hemorrhage.

No abstract

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 β-blockade, and continuation of medical therapy with nitrates and calcium antagonists. (Neth Heart J 2008;16: 134-6.)Keywords: Prinzmetal angina, acteylcholine, multifocal spasm A 60-year-old female was awakened early one morning with extreme chest discomfort radiating to both her arms. She felt weak and light-headed and she fainted when she tried to get up. She regained consciousness quickly without sequelae. Upon arrival at the hospital she was without symptoms. The ECG was normal. Physical examination revealed no abnormalities. During her hospital stay she had two more early morning episodes of chest discomfort with inferior ST-segment elevation and second degree as well as complete AV block (figure 1). She is a cigarette smoker with no other classical risk factors. Coronary angiography in the absence of ischaemia revealed a normal left coronary artery and a mild fixed coronary obstruction in the distal segment of the right coronary artery (RCA). The diagnosis of Prinzmetal angina was made. 1 She was treated with calcium antagonists and nitrates. She was referred for percutaneous coronary intervention (PCI) of the non-critical obstruction ( figure 2A), but we decided to perform a provocative test with selective intracoronary infusions of acetylcholine in incremental doses. 2 Infusion of acetylcholine at the third dose level (50 µg) induced diffuse mild vasoconstriction and multifocal hyperreactive vasoconstriction (spasm) in apparently normal coronary segments but not at the site of the alleged culprit lesion (figure 2B). The mild constriction and spasms were promptly resolved by intracoronary nitroglycerin ( figure 2C). We refrained from PCI and advised an intensification of the therapy with calcium antagonists, nitrates, aspirin and statins, and avoidance of β-blockade and smoking. DiscussionThis patient presented with classical Prinzmetal (variant) angina. She is a cigarette smoker with no other classical risk factors. 3 As with acute myocardial infarction, a circadian periodicity is present with attacks recurring at approximately the same time in the 24-hour period. [4][5][6] The attacks are severe and are accompanied by syncope, inferior ST-segment elevation and transient AV block, suggestive of acute transient occlusion of the RCA, a frequent site in Prinzmetal angina. 7 Coronary angiography showed a single non-critical obstruction in the distal part of the RCA. Intuitively we held spasm at this site responsible for the attacks, but later we realised that spasm may develop at sites other than the fixed...

Bicuspid aortic valve (BAV) is the most common congenital cardiac defect causing serious morbidity including valvular dysfunction and thoracic aortic aneurysms (TAA) in around 30% of BAV patients. Cardiological screening of first-degree relatives is advised in recent guidelines given the observed familial clustering of BAV. However, guidelines regarding screening of family members and DNA testing are not unequivocal. The aim of this review is to provide an overview of the literature on echocardiographic screening in first-degree relatives of BAV patients and to propose a model for family screening. In addition, we provide a flowchart for DNA testing. We performed a PubMed search and included studies providing data on echocardiographic screening in asymptomatic relatives of BAV patients. Nine studies were included. In 5.8-47.4% of the families BAV was shown to be familial. Of the screened first-degree relatives 1.8-11% was found to be affected with BAV. Results regarding a potential risk of TAA in first-degree relatives with a tricuspid aortic valve (TAV) were conflicting. The reported familial clustering of BAV underlines the importance of cardiological screening in relatives. After reviewing the available family history, patient characteristics and the results of cardiological screening in relatives, follow-up in relatives with a TAV and/or DNA testing may be advised in a subset of families. In this study we propose a model for the clinical and genetic work-up in BAV families, based on the most extensive literature review on family screening performed until now.