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— Thin filament mutations are reported to cause ≈20% of cases of hypertrophic cardiomyopathy (HCM), and they have been associated with specific phenotypes. However, the frequency of these mutations and their associated phenotype(s) from a large tertiary referral center population are unknown. Methods and Results— DNA was obtained from 389 unrelated patients with HCM. A mutational analysis of all protein coding exons of cardiac troponin T, cardiac troponin I, α-tropomyosin, and cardiac actin was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing. The clinical data were extracted from patient records and maintained independent of the patient genotype. Overall, only 18 patients (4.6%) harbored isolated thin filament mutations: 8 had troponin T mutations, 6 had troponin I mutations, 3 had α-tropomyosin mutations, and 1 had an actin mutation. Of the 12 unique missense mutations identified, 9 (75%) were novel mutations. As a group, patients with thin filament mutations were not significantly different from the rest of the cohort in age at diagnosis, left ventricular wall thickness, left ventricular outflow tract obstruction, or family history of HCM or sudden cardiac death. Conclusions— Mutations in genes encoding thin filament proteins are less prevalent in HCM than previously estimated. Patients with mutations in troponin T, troponin I, α-tropomyosin, and actin do not invariably present with any distinct clinical feature, thus limiting the utility of gene status for risk stratification or of clinical phenotype in guiding individual genetic screening at this time.

Background— Genotype-phenotype correlative studies have implicated 8 particular mutations that cause hypertrophic cardiomyopathy (HCM) as “benign defects,” associated with near-normal survival: N232S, G256E, F513C, V606M, R719Q, and L908V of β-myosin heavy chain ( MYH7 ); S179F of troponin T ( TNNT2 ); and D175N of α-tropomyosin ( TPM1 ). Routine genetic screening of HCM patients for specific mutations is anticipated to provide important diagnostic and prognostic information. The frequency and associated phenotype of these mutations in a large, unselected cohort of HCM is unknown. Methods and Results— A total of 293 unrelated HCM patients were genotyped for the presence of a benign mutation. DNA was obtained after informed consent; specific MHY7, TNNT2 , and TPM1 fragments were amplified by polymerase chain reaction; and the mutations were detected by denaturing high-performance liquid chromatography and automated DNA sequencing. Only 5 (1.7%) of the 293 patients possessed a benign mutation. Moreover, all 5 subjects with an ascribed benign mutation had already manifested clinically severe expression of HCM, with all 5 requiring surgical myectomy, 3 of the 5 having a family history of sudden cardiac death, and 1 adolescent requiring an orthotopic heart transplant. Conclusions— These findings demonstrate the rarity of specific mutations in HCM and challenge the notion of mutation-specific clinical outcomes. Fewer than 2% of the subjects harbored a benign mutation, and those patients with a benign mutation experienced a very serious clinical course.

Abstract Previous studies have reported mortality rates of about 80% in hematopoietic stem cell transplant recipients with diffuse alveolar hemorrhage. This retrospective study describes the clinical course of 48 such patients: mean age 47.7 years, 52% autologous transplant and 67% peripheral stem cell source. The hemorrhage occurred within one month of transplant in 28 patients. Symptoms included dyspnea in 92%, fever in 67%, cough in 56%, and hemoptysis in 15%. Intensive care unit admission was required in 85% and mechanical ventilation in 77%. Most of the patients were treated with intravenous methylprednisolone 1 g daily for 3 days and then tapered off after a median of 22 days. The hospital mortality was 48%. The cause of death was respiratory failure in 15 of the 23 deaths. Mortality was 28% in autologous compared with 70% in allogeneic transplant recipients (p = 0.0040). The mortality rate of patients whose hemorrhage occurred within the first 30 days of transplant was 32% compared with 70% of those with late hemorrhage (p = 0.0096). This study shows that survival rate of hematopoietic stem cell transplant recipients with diffuse alveolar hemorrhage is better than previously reported, and that early onset and autologous transplant are favorable prognostic indicators.

Abstract This retrospective study describes the clinical course of 38 patients with idiopathic pulmonary fibrosis (IPF) admitted to the intensive care unit (ICU). There were 25 males and 13 females who were the mean age of 68.3 ± 11.5 years. Twenty patients were on corticosteroids at the time of admission to the hospital, and 24 had been on home oxygen therapy. The most common reason for ICU admission was respiratory failure. The Acute Physiology and Chronic Health Evaluation III–predicted ICU and hospital mortality rates were 12% and 26%, whereas the actual ICU and hospital mortality rates were 45% and 61%, respectively. We did not find significant differences in pulmonary function or echocardiogram findings between survivors and nonsurvivors. Mechanical ventilation was used in 19 patients (50%). Sepsis developed in nine patients. Multiple organ failure developed in 14% of the survivors and in 43% of the nonsurvivors (p = 0.14). Ninety-two percent of the hospital survivors died at a median of 2 months after discharge. These findings suggest that patients with IPF admitted to the ICU have poor short- and long-term prognosis. Patients with IPF and their families should be informed about the overall outlook when they make decisions about life support and ICU care.

Human cancer cells with a mutated p53 tumor-suppressor gene have a selective growth advantage and may exhibit resistance to ionizing radiation and certain chemotherapeutic agents. To examine the prognostic value of mutations in the p53 gene, a cohort of 90 Midwestern Caucasian breast cancer patients were analyzed with methodology that detects virtually 100% of all mutations. The presence of a p53 gene mutation was by far the single most predictive indicator for recurrence and death (relative risks of 4.7 and 23.2, respectively). Direct detection of p53 mutations had substantially greater prognostic value than immunohistochemical detection of p53 overexpression. Analysis of p53 gene mutations may permit identification of a subset of breast cancer patients who, despite lack of conventional indicators of poor prognosis, are at high risk of early recurrence and death.