Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease.

In sickle cell disease (SCD), abnormal microvascular function combined with chronic anaemia predisposes patients to perfusion-demand mismatch. We hypothesized that skeletal muscle and myocardial perfusion, normalized to the degree of anaemia, is reduced at basal-state compared to controls, and that this defect is ameliorated by hydroxycarbamide (HC; also termed hydroxyurea) therapy. Twenty-one SCD patients, of whom 15 were treated with HC, and 27 controls underwent contrast-enhanced ultrasound (CEU) perfusion imaging of the forearm as well as the myocardium. HC treatment was associated with lower white cell and reticulocyte counts, and higher fetal haemoglobin and total haemoglobin levels. When corrected for the degree of anaemia in SCD patients, skeletal flow in HC-treated patients was significantly higher than in untreated SCD patients (217·7 ± 125·4 vs. 85·9 ± 40·2, P = 0·018). Similarly, when normalized for both anaemia and increased myocardial work, resting myocardial perfusion was also significantly higher in HC-treated patients compared with untreated SCD patients (0·53 ± 0·47 vs. 0·13 ± 0·07, P = 0·028). Haemoglobin F (HbF) levels correlated with skeletal muscle microvascular flow (r = 0·55, P = 0·01). In conclusion, patients with SCD not on HC therapy have resting flow deficits in both skeletal muscle and myocardial flow. HC therapy normalizes flow and there is a direct correlation with HbF levels. Clinical trial registration ClinicalTrials.gov Identifier: NCT01602809; https://clinicaltrials.gov/ct2/show/NCT01602809?term=sACHDEV&rank=9.

Left atrial volumetric remodeling is predictive of functional capacity in nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: The left atrium is afterload sensitive, responding to immediate changes in left ventricular (LV) diastolic pressure, and left atrial volumetric remodeling has been reported in conditions associated with abnormal diastolic function. We examined the relationship between left atrial volumetric remodeling and objective measures of exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (HCM). METHODS: We compared LA volume indices, other 2-dimensional and Doppler echocardiographic parameters, invasive hemodynamic measures, and magnetic resonance imaging (MRI)-derived LV mass with exercise duration, maximal oxygen uptake (MV* O2), anaerobic threshold (AT), and ventilatory efficiency (VE/V* CO2 slope) in 43 patients with nonobstructive HCM. Patients underwent cardiac catheterization within 48 hours and metabolic stress testing within 1 week of their echocardiogram and MRI examinations. RESULTS: Left atrial volume at end-ventricular systole (LA max) and end-atrial emptying (LA min) correlated with MV* O2 (r = -0.39, P < .01 for both), AT (r = -0.42, r = -0.39, respectively, P < .01 for both), and VE/V* CO2 slope (r = 0.45, P = .003; r = 0.41, P = .008). Patients with an LA max > or =33 mL/m2 had significantly lower MV* O2 (P = .025) and AT levels (P = .017) and higher VE/V* CO2 slope levels (P = .004) as compared with patients with a smaller LA size. In multivariate analysis, MRI-determined LV mass, which was not a univariate correlate of exercise tolerance, provided additional effect when combined with LA volume index. CONCLUSIONS: Left atrial volumetric remodeling predicts exercise capacity in nonobstructive HCM and may reflect chronic LV diastolic burden. This simple noninvasive measure of LA size may provide a long-term indication of the effects of chronically elevated filling pressures in patients with HCM and further studies testing its prognostic value are necessary.

Changes in left ventricular diastolic function of asymptomatic hereditary hemochromatosis subjects during five years of follow-up.

We have previously reported that left ventricular (LV) diastolic function in those with cardiac asymptomatic hereditary hemochromatosis (HH) is similar to that of volunteer control (VC) subjects, despite a presence of augmented left atrial contractile function. However, concern still exists that those with HH might gradually develop LV diastolic dysfunction despite receiving conventional phlebotomy treatment. To address this concern, we prospectively monitored the LV diastolic function of those with HH and VCs during a 5-year period. A total of 14 subjects with newly diagnosed HH (age 51 ± 12 years, 4 women, group A), 20 with chronic HH (age 51 ± 9 years, 7 women, group B), and 18 VCs (age 50 ± 8 years, 6 women, group C) successfully completed both the baseline evaluation of LV diastolic function, including tissue Doppler imaging, strain rate analysis with color-coded tissue Doppler, and the same studies repeated at 5 years of follow-up. All those with HH were New York Heart Association functional class I, were positive for the C282Y homozygote, and received conventional phlebotomy therapy. No VC had HH genetic mutations. The measures of LV diastolic function were comparable among the groups at 5 years of follow-up by analysis of variance. The echocardiographic measures of active left atrial contraction tended to decrease in the HH groups at 5 years of follow-up from baseline. In conclusion, LV diastolic function does not significantly deteriorate statistically during a 5-year period in subjects with cardiac asymptomatic HH after conventional phlebotomy treatment, regardless of their treatment history.

FOS expression in blood as a LDL-independent marker of statin treatment.

OBJECTIVES: The expression of FOS, a gene critical for monocyte and macrophage function, can be inhibited by statins through the disruption of a cholesterol-independent signaling pathway. In this pilot study, we hypothesized that blood FOS mRNA levels will be sensitive to statin treatment independent of LDL cholesterol levels. METHODS: Three cohorts at increased risk of or with cardiovascular disease (CVD) were studied. Blood FOS mRNA levels were measured before and after statin treatment or in patients under stable treatment. RESULTS: Statin treatment for three months significantly reduced blood FOS mRNA and LDL cholesterol levels. However, in subjects with similar LDL levels achieved by different doses of long term statin treatment, there was an inverse relationship between statin dose and FOS expression. CONCLUSIONS: FOS mRNA levels appear to be a sensitive marker of statin treatment that is dissociated from cholesterol levels.

Myocardial strain decreases with increasing transmurality of infarction: a Doppler echocardiographic and magnetic resonance correlation study.

BACKGROUND: Regional abnormalities in myocardial systolic function can be detected with myocardial strain measurements derived from Doppler tissue echocardiography. We studied longitudinal strain measurements in patients with evidence of myocardial infarction by cardiac magnetic resonance imaging to determine whether end-systolic strain could identify the severity of the infarction. METHODS: A total of 20 patients with chronic myocardial infarctions and 10 healthy volunteers underwent 2-dimensional echocardiography and cardiac magnetic resonance with delayed gadolinium (Gd) gadopentetate dimeglumine (DTPA) contrast hyperenhancement. Delayed Gd hyperenhancement was graded using the following scale: 0 = none, 1 = less than 25%, 2 = 26% to 50%, 3 = 51% to 75%, and 4 = greater than 75%. RESULTS: There was a progressive decrease in peak systolic strain in the infarct segments as the transmural extent of infarction increased. When compared with the peak systolic strain in remote segments without evidence of infarction (-19.7 +/- 0.9), the strain was significantly lower in segments with greater than 25% Gd hyperenhancement (grade 2, -14.8 +/- 1.1, P = .001; grade 3, -12.9 +/- 2.1, P = .001; grade 4, -9.1 +/- 2.0, P < .001). CONCLUSIONS: In patients with chronic myocardial infarctions, strain measurements with echocardiography show a graded response of decreasing regional strain in segments with increasing transmural extent of infarction defined by Gd hyperenhancement.