Citations

Learning Objectives Analyze the clinical trial data for the treatment of breast cancer. Evaluate the risk of cardiotoxicity associated with the use of trastuzumab. Design and conduct a practical approach to managing patients with trastuzumab-associated cardiotoxicity. This article is available for continuing medical education credit at CME.TheOncologist.com.

Background— Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease characterized by a diverse clinical and phenotypic spectrum. This study reports the prevalence, morphology, clinical course, and management of an underrecognized subgroup of HCM patients with left ventricular apical aneurysms. Methods and Results— Of 1299 HCM patients, 28 (2%) were identified with left ventricular apical aneurysms, including a pair of identical twins. Aneurysms were recognized at a wide age range (26 to 83 years), including 12 patients (43%) who were ≤50 years of age. Apical aneurysms varied considerably in size (maximum dimension, 10 to 66 mm), were dyskinetic/akinetic with thin rims, and were associated with transmural (and often more extensive) myocardial scarring identified by late gadolinium enhancement cardiovascular magnetic resonance. Apical aneurysms were recognized by echocardiography in only 16 of 28 patients (57%) but by cardiovascular magnetic resonance in the 12 patients undetected by echocardiography. Left ventricular chamber morphology varied; however, 19 patients (68%) showed an “hourglass” contour, with midventricular hypertrophy producing muscular narrowing and intracavitary gradients in 9 patients (74±42 mm Hg). Sarcomeric protein missense mutations known to cause other phenotypic expressions of HCM were present in 3 patients. Over 4.1±3.7 years of follow-up, 12 patients (43%) with left ventricular apical aneurysms experienced adverse disease complications (event rate, 10.5%/y), including sudden death, appropriate implantable cardioverter-defibrillator discharges, nonfatal thromboembolic stroke, and progressive heart failure and death. Conclusions— Patients with left ventricular apical aneurysms represent an underappreciated subset in the heterogeneous HCM disease spectrum with important clinical implications, often requiring a high index of suspicion and cardiovascular magnetic resonance for identification. Apical aneurysms in HCM are associated with substantial cardiovascular morbidity and mortality and raise novel treatment considerations.

Object Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression. Results Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006). Conclusions In the FIA study, among the affected patients' FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.

Background Evolving technologies of proximal anastomosis devices meet the endeavor of surgeons to minimize manipulation of the ascending aorta during surgical myocardial revascularization. The objective of this study was to compare the patency rate of the saphenous vein coronary bypass grafts in which the proximal anastomoses were performed with automatic connector devices to the suture technique. Methods From September 2002 through July 2003, 86 patients underwent coronary artery bypass grafting with at least 1 vein graft anastomosed to the ascending aorta with the Symmetry G2 connector. Six-month clinical and angiographic follow-up, including Core-Lab quantitative coronary angiography (QCA) and corrected TIMI frame count (CTFC), was performed. Results Eighty patients had at least 1 connector successfully implanted. Freedom from MACE (cardiac mortality myocardial infarction and target vessel reintervention) was 72/80 (90%). Six patients underwent a target vessel reintervention on the connector grafts. Six-month (mean 193 ± 36 days) angiography patency rates for the connector grafts were 72/81 (88.89%), 37/40 (92.5%) in sutured grafts, and 60/62 (96.8%) in arterial grafts. By QCA, 64/65 (98.5%) patent connector-grafts were free from more than 50% stenosis (1 connector-graft with a 51% stenosis). CTFC showed 65/65 (100%) patent connector-grafts with nonrestrictive flow. Conclusions Saphenous vein grafts anastomosed to the aorta with the Symmetry G2 connector have early and midterm patency rates comparable to the conventional sutured anastomoses. These results support the efficiency of the second generation of symmetry aortic connectors.

Background— Few studies have compared medium-term outcomes for drug-eluting stents (DES) and bare metal stents, and most are relatively small randomized controlled trials. Furthermore, since the introduction of DES, there has been increased use and duration of use of clopidogrel, statins, and other evidence-based therapies. The purpose of the present study was to compare outcomes for patients who underwent stenting in the eras before and after the introduction of DES. Methods and Results— New York state patients undergoing stenting in all nonfederal hospitals in the state were studied. Patients were excluded if they had a previous revascularization. Risk factors that were significant predictors of adverse outcomes were used to adjust adverse outcome rates. The study included 11 436 patients who received stents between October 1, 2002, and March 31, 2003, and 12 926 patients who underwent stenting between October 1, 2003, and March 31, 2004. Death rates, the combined end point of death and myocardial infarction (MI), nonfatal MI requiring readmission, target vessel revascularization, and target lesion revascularization were compared at 2 years. Patients in the DES era had significantly better risk-adjusted outcomes for death/MI (adjusted hazard ratio, 0.90; 95% confidence interval, 0.83 to 0.97), 9.9% versus 10.8%; nonfatal MI requiring readmission (adjusted hazard ratio, 0.86; 95% confidence interval, 0.76 to 0.97); target vessel revascularization (adjusted hazard ratio, 0.60; 95% confidence interval, 0.56 to 0.64), 11.2% versus 17.9%; and target lesion revascularization (hazard ratio, 0.55; 95% confidence interval, 0.51 to 0.59), 8.4% versus 14.7%. Conclusions— Patients in the DES era experienced lower rates of death/MI, nonfatal MI, target vessel revascularization, and target lesion revascularization, but there were no differences in the rates of death. These improvements are likely a result of increased use of clopidogrel, statins, and dual antiplatelet therapy, in addition to the introduction of DES.

Background and Purpose— Evidence supports a substantial genetic contribution to the risk of intracranial aneurysm (IA). The purpose of this study was to identify chromosomal regions likely to harbor genes that contribute to the risk of IA. Methods— Multiplex families having at least 2 individuals with “definite” or “probable” IA were ascertained through an international consortium. First-degree relatives of individuals with IA who were at increased risk of an IA because of a history of hypertension or present smoking were offered cerebral magnetic resonance angiography. A genome screen was completed using the Illumina 6K SNP system, and the resulting data from 192 families, containing 1155 genotyped individuals, were analyzed. Narrow and broad disease definitions were used when testing for linkage using multipoint model-independent methods. Ordered subset analysis was performed to test for a gene×smoking (pack-years) interaction. Results— The greatest evidence of linkage was found on chromosomes 4 (LOD=2.5; 156 cM), 7 (LOD=1.7; 183 cM), 8 (LOD=1.9; 70 cM), and 12 (LOD=1.6; 102 cM) using the broad disease definition. Using the average pack-years for the affected individuals in each family, the genes on chromosomes 4 (LOD=3.5; P =0.03), 7 (LOD=4.1; P =0.01) and 12 (LOD=3.6; P =0.02) all appear to be modulated by the degree of smoking in the affected members of the family. On chromosome 8, inclusion of smoking as a covariate did not significantly strengthen the linkage evidence, suggesting no interaction between the loci in this region and smoking. Conclusions— We have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene×smoking interaction with 3 of the loci.

Patients with hypertension exhibit impaired energetic coupling between the ventricle and the arterial system, leading to reduced cardiac mechanic efficiency and exercise capacity. We tested whether blood pressure normalization with current antihypertensive therapy can improve arterioventricular coupling. Eighteen hypertensive patients without other cardiovascular disease were examined before and after antihypertensive therapy. Transthoracic echocardiography was performed. Central aortic pressure waveforms, including end-systolic pressure, were derived from radial artery applanation tonometry. Afterload was increased with isometric handgrip exercise. Central aortic end-systolic pressure and ventricular volumes at rest and handgrip were used to calculate ventricular elastance, effective arterial elastance, arterioventricular coupling (effective arterial elastance/ventricular elastance), and mechanical efficiency. After 142±67 days, systolic blood pressure decreased from 150.9±14.6 to 119.8±9.2 mm Hg ( P <0.00001), diastolic blood pressure from 85.9±14.8 to 68.8±8.4 mm Hg ( P =0.00002), and cardiac output from 5.8±1.7 to 4.9±1.8 L/min ( P =0.03). Resting left ventricular end-systolic volume, ejection fraction, and septal thickness did not change. Ventricular elastance increased from 1.7±1.0 to 3.2±1.4 mm Hg/mL ( P =0.00002), whereas effective arterial elastance decreased from 1.4±0.5 to 1.2±0.4 mm Hg/mL ( P =0.02). Effective arterial elastance/ventricular elastance decreased in all patients, from 1.1±0.8 to 0.4±0.2 ( P =0.0002). Efficiency improved at rest (72.9±5.8% versus 83.5±5.7%; P <0.00001) and during handgrip (63.5±7.8% versus 78.9±7.1%; P <0.00001). In hypertensive patients, optimal brachial and central blood pressure reduction shifts arterioventricular coupling from cardiac output maximization to ventricular mechanical efficiency optimization. This occurs before significant changes in ventricular geometry and may be responsible for early clinical improvements.