Citations

Background— Adult patients with hypertrophic cardiomyopathy (HCM) may develop concomitant atherosclerotic coronary artery disease (CAD). There is a paucity of data on the clinical outcomes of HCM patients who have CAD. Methods and Results— We examined the outcome of 433 adult patients with HCM according to the presence and severity of CAD. All patients were aged ≥21 years, had a left ventricular ejection fraction of ≥50%, and were without a history of prior surgical revascularization (mean age, 63 years; 212 men). Compared with HCM patients with mild-to-moderate or no CAD, those with severe CAD demonstrated markedly reduced survival. Ten-year overall survival was 46.1%, 70.5%, and 77.1% for patients with severe, mild-to-moderate, and no CAD, respectively (unadjusted P =0.0001; adjusted P =0.0006). For the end point of cardiac death, this survival was 62.3%, 81.0%, and 80.9% (unadjusted P =0.009; adjusted P =0.004). For the end point of sudden cardiac death, this survival was 77.4%, 93.2%, and 90.3% (unadjusted P =0.01; adjusted P =0.01). The presence of severe CAD also was highly predictive of these events (risk ratio for respective event: 2.31, 2.15, and 2.77) in multivariate models that additionally identified age, prior stroke, hyperlipidemia, and atrial fibrillation as significant covariates. Conclusions— Among adult patients with HCM who undergo coronary angiography, those who have concomitant severe CAD are at increased risk of death. This risk far exceeds historical death rates of CAD patients with normal left ventricular function.

Background and Purpose— Anecdotal evidence exists for at least 2 subpopulations of intracranial saccular aneurysms, namely, those that may form rapidly and rupture when small versus those that enlarge slowly and may rupture particularly when ≥10 mm in diameter. We sought to determine whether the endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), implicated in cardiovascular disease susceptibility, could facilitate differentiation between small (≤5 mm) versus large (≥10 mm) ruptured aneurysms. Methods— In accordance with institutional guidelines, clinical data were recorded prospectively and genomic DNA was isolated from blood samples obtained from 52 aneurysmal subarachnoid hemorrhage (SAH) patients (cases) and 90 randomly selected controls. Samples were assayed for eNOS gene promoter T-786C SNP with the use of gene microarray technology. Statistical analyses included multiple logistic regression. Results— Although there was no difference in genotype distributions between cases and controls, all 13 patients with large aneurysms were ( T / C ) heterozygous for the polymorphism, while 9 of 22 patients (41%) with small aneurysms were ( T / T or C / C ) homozygous ( P =0.01). The mean (±SD) ruptured aneurysm diameter among all heterozygotes (8.5±5.2 mm) was significantly greater than that for C / C (6.0±2.3 mm) or T / T (4.7±1.8 mm) homozygotes ( P =0.04). With the use of multivariate analysis, heterozygosity remained significantly associated with aneurysm size ≥10 mm ( P =0.03). Conclusions— The eNOS T-786C SNP distinguishes genetically between small and large ruptured aneurysms. Although not predictive of SAH in the population at large, our data suggest that among persons with known intracranial aneurysms, eNOS T-786C genotype may be a factor influencing the size at which an aneurysm ruptures, a finding that should be taken into consideration along with other anatomic features of the aneurysm.

Abstract Rarely, myelodysplastic syndrome (MDS) is complicated by an acquired form of α-thalassemia (α-thalassemia in myelodysplastic syndrome [ATMDS]) characterized by hypochromic, microcytic, anisopoikilocytic red blood cells with hemoglobin H (HbH) inclusions. Acquired mutations in ATRX, a chromatin remodeling gene, have recently been found in 12 patients with typical features of ATMDS, though they have not been detected in MDS patients with similar red blood cell findings but little HbH. The α-globin genes themselves have appeared normal in all ATMDS patients studied to date. Here we characterize the molecular defect in a unique MDS patient with rare HbH inclusions in which an abnormal clone lost a greater than 1.9-Mb segment of the telomeric region of the short arm of one allele of chromosome 16, including both α-globin genes. Red blood cell changes associated with this acquired somatic genotype (––/αα) are surprisingly severe, demonstrating that a minor globin chain imbalance may be unexpectedly deleterious during the abnormal erythropoiesis that occurs in the context of MDS.

Abstract Heterogeneity in the clinical behavior of patients with chronic lymphocytic leukemia (CLL) makes it difficult for physicians to accurately identify which patients may benefit from an early or more aggressive treatment strategy and to provide patients with relevant prognostic information. Given the potential efficacy of newer therapies and the desire to treat patients at “optimum” times, it is more important than ever to develop sensitive stratification parameters to identify patients with poor prognosis. The evolution of risk stratification models has advanced from clinical staging and use of basic laboratory parameters to include relevant biologic and genetic features. This article will review the dramatic progress in prognostication for CLL and will propose statistical modeling techniques to evaluate the utility of these new measures in predictive models to help determine the optimal combination of markers to improve prognostication for individual patients. This discussion will also elaborate which markers and tools should be used in current clinical practice and evaluated in ongoing clinical trials.