Prognostic Implications of Point-of-Care and Serial B-type Natriuretic Peptide Levels in Patients With Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HC) is a heterogenous disease with a variable clinical course. Predictors of long-term adverse cardiovascular events are needed. Our objectives were to determine the long-term prognostic value of a single and serial point of care (POC) B-type natriuretic-peptide (BNP) measurements in HC. One hundred and eleven ambulatory patients with HC (mean age 53 ± 16 years) were prospectively recruited over a 2-year period (2004 to 2006). A clinical assessment, comprehensive echocardiogram, and a POC BNP level was obtained at baseline and at a 1- to 2-year follow-up. They were subsequently followed for the occurrence of major adverse cardiac events (MACE). The median baseline BNP concentration was 114 pg/ml (range 5.3 to 1550 pg/ml). During a mean follow-up of 6.2 ± 3.4 years, 42 patients (38%) had a MACE. In a multivariable Cox model including clinical and echocardiographic predictors, logBNP (HR 4.30; 95% confidence interval 1.97 to 9.37, p <0.001) and left ventricualr ejection fraction (LVEF) (HR 0.96; 95% confidence interval 0.94 to 0.99, p = 0.011) remained significant predictors of MACE. Nested models demonstrated incremental prognostic value of logBNP for MACE (chi-square increased from 4.3 to 22.8, p <0.01) over clinical and echocardiographic factors. Patients with persistently elevated BNP (>100 pg/ml) at baseline and at the second visit were at a higher risk of developing MACE during follow-up (5-year MACE-free survival of 0.91 (SE 0.06) vs 0.45 (SE 0.09), p <0.001). In conclusion, POC BNP levels in patients with HC were predictive of long-term MACE and had independent and incremental value. Patients with persistently elevated BNP levels were at a higher risk of MACE.

Early changes in apical rotation in genotype positive children with hypertrophic cardiomyopathy mutations without hypertrophic changes on two-dimensional imaging.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common form of inherited cardiomyopathy. Echocardiography is the mainstay of screening and disease surveillance, and genetic testing has identified a carrier population without hypertrophy. The aim of this study was to investigate whether changes in left ventricular (LV) function are detectable before the advent of hypertrophy. METHODS: Fourteen children with genotype-positive, phenotype-negative HCM were identified (12 male; median age, 9.14 years; range, 1.91-15.9 years; median weight, 34.6 kg; range, 15-92.1 kg) and compared with age-matched and sex-matched healthy controls. All children underwent full echocardiographic studies using an extensive functional protocol, including two-dimensional dimensions, Doppler tissue imaging, and two-dimensional speckle-tracking echocardiography. RESULTS: There were no differences in LV wall thickness, chamber dimensions, length, and shortening fraction between the groups. Doppler tissue imaging in children with HCM demonstrated mildly reduced septal velocities, notably A' (5.9 cm/sec [range, 4-8.9 cm/sec] vs 6.7 cm/sec [range, 5.2-9.5 cm/sec]; P = .009). Circumferential and longitudinal strain was similar between groups. Mean apical circumferential deformation was increased in the HCM group (-24.6 ± 3.8% vs -22.2 ± 2.5%, P = .04). There were significant increases in basal and apical rotation and LV twist in children with HCM, most marked at the apex (11.7 ± 4.4° vs 5.3 ± 2.5°, P = .0001). On receiver operating characteristic curve analysis, apical rotation > 7° conferred 83% sensitivity and 82% specificity for predicting HCM (area under the curve, 0.919; P = .0001). CONCLUSIONS: Increased LV rotation and twist are present in children with genotype-positive, phenotype-negative HCM. Apical rotation on speckle-tracking echocardiography provides good sensitivity and specificity for the prediction of gene-positive HCM and may be a clinically useful early marker of HCM before the onset of hypertrophy.

Cytomegalovirus infection in childhood-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem disease with significant morbidity and even mortality. Cytomegalovirus (CMV) is a ubiquitous herpesvirus that, similar to SLE, can also lead to significant morbidity and mortality in the immunocompromised host. The relationship between SLE and CMV is complex, with observations suggesting that CMV induces the autoimmunity of SLE in addition to occurring in the immunocompromised host with known SLE. In this article, we first consider CMV infection in the immunocompetent host, and further examine how this infection differs in the patient with SLE. We focus on disease mechanisms, CMV detection and treatment. We review the differences between CMV infection, syndrome and disease, as identifying the correct state will determine the appropriate treatment. We propose guidelines for the screening and management of CMV infection in childhood-onset SLE, and recognize that further study in this population is required to increase our understanding of the interplay between these disease entities.

Determinants of implantable defibrillator discharges in high-risk patients with hypertrophic cardiomyopathy.

OBJECTIVES: To identify the determinants of appropriate and inappropriate implantable cardioverter-defibrillator (ICD) discharges in patients with hypertrophic cardiomyopathy (HCM). DESIGN: Retrospective cohort study. SETTING: ICD clinic at an academic hospital. PATIENTS: 61 patients with HCM who received ICDs for the primary or secondary prevention of sudden cardiac death (SCD). OUTCOME MEASURES: (a) Analysis of appropriate and inappropriate ICD discharges; (b) predictors of ICD discharges. RESULTS: Mean (SD) age at ICD insertion was 46 (18) years (range 10-79). Follow-up time was 40 (27) months (range 7-151). Eight patients experienced an appropriate discharge, occurring 24.5 (13.6) months after ICD insertion. Appropriate ICD intervention was more common in the secondary (36%) than the primary (8%) prevention group (p = 0.02). Inappropriate ICD discharges occurred in 20 (33%) patients. Multivariate Cox regression analysis identified two significant predictors of inappropriate ICD discharges: (a) age <30 years at the time of ICD insertion (hazard ratio (HR) = 3.0 (95% CI 1.1 to 8.0; p = 0.03) and (b) history of atrial fibrillation (HR = 3.1 (95% CI 1.2 to 8.1; p = 0.02). CONCLUSIONS: ICDs are effective in the prevention of SCD in HCM. However, there is a high incidence of inappropriate ICD discharges.

Clinical and echocardiographic determinants of long-term survival after surgical myectomy in obstructive hypertrophic cardiomyopathy.

BACKGROUND: Surgical myectomy has been the standard treatment for patients with drug-refractory obstructive hypertrophic cardiomyopathy. The clinical and echocardiographic predictors of long-term survival and freedom from cardiovascular morbidity after myectomy have been unclear. METHODS AND RESULTS: We studied a consecutive cohort of 338 adult patients (age at operation 47+/-14 [range 18 to 77] years, 60% male) who underwent myectomy at our institution. Preoperative resting left ventricular outflow tract (LVOT) gradient was 66+/-32 mm Hg (range 5 to 158 mm Hg). Early postoperative mortality was 1.5% (5 deaths): 4 deaths occurred between 1978 and 1992, and 1 death occurred between 1993 and 2002. During long-term follow-up, 83% of patients reported an improvement to functional class I or II. The majority of patients (98%) had no resting LVOT gradient. Long-term survival was excellent, with 98+/-1% survival at 1 year, 95+/-1% at 5 years, and 83+/-3% at 10 years after myectomy. Multivariable Cox regression analysis identified 5 predictors of overall mortality: (1) age > or =50 years at surgery (hazard ratio [HR] 2.8, 95% CI 1.5 to 5.1, P=0.001), (2) female gender (HR 2.5, 95% CI 1.5 to 4.3, P=0.0009), (3) history of preoperative atrial fibrillation (HR 2.2, 95% CI 1.2 to 4.0, P=0.008), (4) concomitant CABG (HR 3.7, 95% CI 1.7 to 8.2, P=0.001), and (5) preoperative left atrial diameter > or =46 mm (HR 2.9, 95% CI 1.6 to 5.4, P=0.0008). Significant predictors of late major cardiovascular events found on multivariable analysis were (1) female gender (HR 3.3, 95% CI 2.0 to 5.4, P<0.0001), (2) history of preoperative atrial fibrillation (HR 1.9, 95% CI 1.1 to 3.3, P=0.02), and (3) preoperative left atrial diameter > or =46 mm (HR 2.5, 95% CI 1.5 to 4.3, P=0.0008). CONCLUSIONS: Myectomy provides excellent relief for LVOT obstruction in patients with hypertrophic cardiomyopathy. Preoperative clinical and echocardiographic variables can predict long-term outcome after myectomy.