Effect of nitroglycerin on splanchnic and pulmonary blood volume.

BACKGROUND: Sublingual nitroglycerin (SL NTG) is useful for treating acute decompensated heart failure, possibly by increasing splanchnic capacitance and reducing left ventricular (LV) preload. We evaluated a radionuclide method to study these effects, initially in subjects without heart failure. METHODS AND RESULTS: Red blood cells were labelled by an in vitro method. Abdominal and chest images were obtained at rest, showing relative regional blood volumes. The abdomen was then re-imaged during progressive escalation of intrathoracic pressure using continuous positive airway pressure to assess baseline splanchnic capacitance (pressure-volume relationship, PVR) and compliance (slope of PVR). The procedure was repeated after 0.6 mg SL NTG, followed by chest images. Relative splanchnic blood volume increased at rest after SL NTG (P < .002), signifying an increase in splanchnic capacitance. The slope of the splanchnic PVR decreased in proportion to the baseline PVR (P = .0014), signifying increased compliance. The relative pulmonary blood volume decreased in proportion to the increase in splanchnic blood volume (P = .01). CONCLUSIONS: A semi-quantitative radionuclide method demonstrated the effect of SL NTG for increasing splanchnic capacitance and compliance, with a proportional decrease in pulmonary blood volume. These data may be applied to quantitatively evaluate the importance of splanchnic vasodilation as a mechanism of LV preload reduction in the treatment of heart failure. CLINICAL TRIALS REGISTRATION: NCT02425566.

Reversible, regional ST-segment elevation due to chylothorax.

Chylothorax is an uncommon complication of thoracic surgery and, to our knowledge, has never been documented as a cause of dynamic ST-segment elevation (STE). A 63-year-old woman with history of right pneumonectomy presented with chest pain and regional STE on 12-lead electrocardiogram (ECG). Normal troponin-I and a computed tomography (CT) scan showing a large right hemithoracic fluid collection indicated the unique cause of STE, which resolved after thoracentesis, was pericardial inflammation and cardiac compression from chylothorax. This case emphasizes nuances of ECG interpretation in the context of regional STE and explores the pathophysiology that links chylothorax with acute pericarditis.

Myocardial T1 Measurement Predicts Beneficial LV Remodeling After Long-Term Heart Failure Therapy.

BACKGROUND: The myocardial longitudinal relaxation time (T1) on cardiac magnetic resonance imaging (CMR) can quantify myocardial fibrosis in the presence or absence of visually detectable late gadolinium (Gd) enhancement (LGE). Mineralocorticoid receptor antagonist (MRA) treatment produces beneficial remodeling in nonischemic dilated cardiomyopathy (NIDCM). We assessed the hypothesis that interstitial myocardial fibrosis measured with the use of CMR predicts left ventricular (LV) beneficial remodeling in NIDCM after heart failure (HF) treatment including MRAs. METHODS AND RESULTS: Twelve patients with NIDCM, on stable beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor-blocking therapy, were studied before and after 6-29 months of treatment with MRAs, by means of CMR assessment of LV structure, function, and T1 from standard Look-Locker sequences (T1LL). All patients had depressed cardiac function, dilated left ventricles, and no visual LGE. After adding MRA to HF treatment, the LV ejection fraction increased and the LV end-systolic volume index (LV end-systolic volume/m2) decreased in all patients (P < .0001). This this was inversely proportional to the baseline myocardial T1LL (r = -0.65; P = .02). CONCLUSION: Myocardial T1LL, in the absence of visually detectable LGE, was quantitatively related to the degree of beneficial LV remodeling achieved in response to adding MRA to a HF regimen.

Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy.

BACKGROUND: Cardiac magnetic resonance (CMR) and [(11)C]acetate positron emission tomography (PET) were used to assess the hypothesis that patients with nonischemic dilated cardiomyopathy (NIDCM) have decreased subendocardial perfusion reserve and impaired oxidative metabolism, consistent with the concept of "energy starvation" in heart failure (HF). METHODS AND RESULTS: CMR myocardial perfusion was evaluated in 13 NIDCM patients and 15 control subjects with coronary risk factors and normal myocardial perfusion. The NIDCM patients underwent [(11)C]acetate PET. The myocardial perfusion index (MPI) was calculated as the normalized rate of myocardial signal augmentation following gadolinium contrast injection. Hyperemic transmural, subendocardial, and subepicardial MPI were reduced in NIDCM compared with control subjects [0.13 vs 0.18 (P < .001), 0.13 vs 0.17 (P < .001), and 0.13 vs 0.17 (P = .008), respectively]. The subendocardial perfusion reserve was 1.59 ± 0.21 vs 1.86 ± 0.32 for the subepicardium (P = .002), demonstrating reduced perfusion reserve. The myocardial oxidative metabolic rate (kmono) per unit demand (rate-pressure product) was reduced in proportion to perfusion reserve (P = .02) CONCLUSIONS: Impaired subendocardial perfusion reserve in NIDCM confirmed results previously attained only in animal models. Impaired perfusion and impaired oxidative metabolism are consistent with subendocardial energy starvation in HF.

Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial.

CONTEXT: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy. OBJECTIVE: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. DESIGN, SETTING, AND PATIENTS: A phase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011. INTERVENTION: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group). MAIN OUTCOME MEASURES: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory. RESULTS: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n = 61 in BMC group and n = 31 in placebo group). Changes in LVESV index (-0.9 mL/m(2) [95% CI, -6.1 to 4.3]; P = .73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P = .17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P = .84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement. CONCLUSION: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00824005.

Myocardial Perfusion and Viability Imaging in Coronary Artery Disease: Clinical Value in Diagnosis, Prognosis, and Therapeutic Guidance.

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Noninvasive imaging tests play a significant role in diagnosing coronary artery disease, as well as risk stratification and guidance for revascularization. Myocardial perfusion imaging, including single photon emission computed tomography and positron emission tomography, has been widely employed. In this review, we will review test accuracy and clinical significance of these methods for diagnosing and managing coronary artery disease. We will further discuss the comparative usefulness of other noninvasive tests-stress echocardiography, coronary computed tomography angiography, and cardiac magnetic resonance imaging-in the evaluation of ischemia and myocardial viability.

Modification of ventriculo-arterial coupling by spironolactone in nonischemic dilated cardiomyopathy.

AIMS: We sought to clarify the role of ventriculo-arterial (V-A) coupling in the treatment of nonischemic dilated cardiomyopathy (NIDCM) by adding a mineralocorticoid receptor antagonist (MRA) to conventional anti-failure therapy. METHODS AND RESULTS: We employed cardiac magnetic resonance imaging to quantify left ventricular (LV) contractility and V-A coupling in normal subjects at rest (n = 11) and in patients with NIDCM (n = 12) before and after long term anti-failure therapy, in which MRA was added to conventional anti-failure therapy. After ≥6 months' treatment in NIDCM patients, LV volumes and mass decreased, and the LV ejection fraction increased from a median of 24% (17, 27) (interquartile range IQR) to 47 (42, 52) (P < 0.002), with a marked reduction in arterial elastance (Ea) from 2.89 mmHg/mL (2.34, 4.0) to 1.50 (1.29, 1.95) (P < 0.002), similar to Ea of normal subjects, 1.53 (1.34, 1.67) (P > 0.05). The V-A coupling ratio, Ea/end-systolic elastance (single-beat method), decreased by -1.08 (-1.96, -0.55), (P = 0.003), as did Ea/end-systolic pressure/end-systolic pressure ratio, -0.54 (0.35, 0.87), (P = 0.002). The preload recruitable stroke work (PRSW) increased as did PRSW indexed for Ea (both P = 0.002), which reflected 'total circulatory performance'. CONCLUSIONS: In NIDCM, adding MRA to conventional anti-failure therapy markedly improved LV ejection fraction and reduced peripheral vascular resistance, due to both improved LV contractility and especially to enhanced V-A coupling, as Ea decreased to normal. Total circulatory performance was a sensitive indicator of both LV pump performance and the arterial loading conditions.

Timing of Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy.

BACKGROUND: Mineralocorticoid receptor antagonist (MRA) treatment produces beneficial left ventricular (LV) remodeling in nonischemic dilated cardiomyopathy (NIDCM). This study addressed the timing of maximal beneficial LV remodeling in NIDCM when adding MRA. MATERIALS AND METHODS: We studied 12 patients with NIDCM on stable ß-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor-blocking therapy who underwent cardiac magnetic resonance imaging before and after 6-31 months of continuous MRA therapy. RESULTS: At baseline, the LV ejection fraction (LVEF) was 24% (19-27); median [interquartile range]. The LV end-systolic volume index (LVESVI) was 63 ml (57-76) and the LV stroke volume index (LVSVI) was 19 ml (14-21), all depressed. After adding MRA to the HF regimen, the LVEF increased to 47% (42-52), with a decrease in LVESVI to 36 ml (33-45) and increase in LVSVI to 36 ml (28-39) (for each, P < 0 .0001). Using generalized least squares analysis, the maximal beneficial remodeling (defined by maximal increase in LVEF, the maximal decrease in LVESVI and maximal increase in LVSVI) was achieved after approximately 12-16 months of MRA treatment. CONCLUSIONS: Adding MRA to a standard medical regimen for NIDCM resulted in beneficial LV remodeling. The maximal beneficial remodeling was achieved with 12-16 months of MRA therapy. These results have implications for the timing of other advanced therapies, such as placing internal cardioverter-defibrillators.

CT-based attenuation correction versus prone imaging to decrease equivocal interpretations of rest/stress Tc-99m tetrofosmin SPECT MPI.

BACKGROUND: The purpose of this study was to compare stress supine single photon emission computed tomography (SPECT) imaging with attenuation correction (AC) via computed tomography-based attenuation maps with stress prone SPECT imaging with regard to the rate of equivocal interpretation of rest/stress myocardial perfusion imaging. METHODS AND RESULTS: Interpretations for 324 consecutive patients referred for rest/stress myocardial perfusion imaging were performed by use of the following sets of poststress SPECT images: supine with no AC (NC), supine NC/AC, supine NC/prone, and all images. The number of equivocal studies decreased with additional imaging: supine NC, 40%; supine NC/prone, 18%; supine NC/AC, 11%; and all images, 8%. The supine NC/AC sets of images reduced the number of defects to a greater extent than the supine NC/prone images for all patients (P = .01), men (P = .002), and women (P = .425). For the inferior (but not the anterior) wall, the percent decrease in defects with supine NC/AC images was lower as compared with supine NC/prone images. CONCLUSION: Interpretation with all images resulted in the fewest equivocal studies. The supine NC/AC images reduced the number of equivocal studies to a greater extent than the supine NC/prone images. AC and prone imaging were more helpful in men than women and were more helpful to resolve inferior than anterior wall defects. Adding prone imaging to supine imaging without and with AC does not significantly alter the number of equivocal interpretations.

Myocardial oxidative metabolic supply-demand relationships in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Nonischemic dilated cardiomyopathy (NIDCM) is associated with left ventricular remodeling, hypertrophy, and mitochondrial metabolic abnormalities in vitro. We evaluated the hypothesis that energy supply, as judged by the rate of myocardial oxidative metabolism, is inadequate to meet oxygen demand in patients with NIDCM compared with normal subjects. METHODS AND RESULTS: We used positron emission tomography to determine the myocardial carbon 11 acetate decay rate (kmono) as an index of energy supply, and we compared kmono with the rate-pressure product (RPP) as an index of metabolic demand in 7 patients with NIDCM and 7 normal subjects. The mean kmono value (SEM) was 0.060 +/- 0.006 min(-1) in NIDCM patients versus 0.054 +/- 0.002 in normal subjects (P = not significant). The RPP was 9949 +/- 931 beats/min.mm Hg in NIDCM patients and 6521 +/- 476 in normal subjects (P = .007). The relationship of kmono to this index of demand (kmono/RPP) was 6.2 x 10(-6) in NIDCM patients but was 8.5 x 10(-6) in normal subjects (P = .003). Thus RPP, as an index of myocardial oxygen demand, was poorly matched by the rate of oxidative metabolism in those patients with NIDCM. The kmono was closely related to RPP in normal subjects (r = 0.83, P = .02) but not in NIDCM patients. Furthermore, there was no significant relationship between kmono and wall stress as another index of oxygen demand. CONCLUSIONS: These results are consistent with a mitochondrial metabolic abnormality in heart failure. This metabolic mismatch detected by positron emission tomography may contribute to the pathophysiology of congestive heart failure and left ventricular remodeling.

Selection of patients for heart transplantation in the current era of heart failure therapy.

OBJECTIVES: We sought to assess the relationship between survival, peak exercise oxygen consumption (VO(2)), and heart failure survival score (HFSS) in the current era of heart failure (HF) therapy. BACKGROUND: Based on predicted survival, HF patients with peak VO(2) <14 ml/min/kg or medium- to high-risk HFSS are currently considered eligible for heart transplantation. However, these criteria were developed before the widespread use of beta-blockers, spironolactone, and defibrillators-interventions known to improve the survival of HF patients. METHODS: Peak VO(2) and HFSS were assessed in 320 patients followed from 1994 to 1997 (past era) and in 187 patients followed from 1999 to 2001 (current era). Outcomes were compared between these two groups of patients and those who underwent heart transplantation from 1993 to 2000. RESULTS: Survival in the past era was 78% at one year and 67% at two years, as compared with 88% and 79%, respectively, in the current era (both p < 0.01). One-year event-free survival (without urgent transplantation or left ventricular assist device) was improved in the current era, regardless of initial peak VO(2): 64% vs. 48% for peak VO(2) <10 ml/min/kg (p = 0.09), 81% vs. 70% for 10 to 14 ml/min/kg (p = 0.05), and 93% vs. 82% for >14 ml/min/kg (p = 0.04). Of the patients with peak VO(2) of 10 to 14 ml/min/kg, 55% had low-risk HFSS and exhibited 88% one-year event-free survival. One-year survival after transplantation was 88%, which is similar to the 85% rate reported by the United Network for Organ Sharing for 1999 to 2000. CONCLUSIONS: Survival for HF patients in the current era has improved significantly, necessitating re-evaluation of the listing criteria for heart transplantation.

Pilot study of a Web-based compliance monitoring device for patients with congestive heart failure.

BACKGROUND: Web-based home care monitoring systems can assess medication compliance, health status, quality of life, and physiologic parameters. They may help overcome some of the limitations associated with current congestive heart failure management models. OBJECTIVES: This pilot study compared the effects of a self-care and medication compliance device, linked to a Web-based monitoring system, to the effects of usual care alone on compliance with recommended self-care behaviors; medication taking; quality of life; distance walked during a 6-minute walk test; and New York Heart Association Functional Class. We also assessed patient experiences living with the compliance device. METHODS: We enrolled 18 patients with Functional Class II-III congestive heart failure in an urban VA Medical Center. The patients were randomized into 2 groups. Group A received usual care plus the compliance device. Group B (controls) received usual care only. Data were collected using the compliance device, the Heart Failure Self-Care Behavior Scale, pill counts, 6-minute walk test, and the Minnesota Living with Heart Failure Questionnaire at baseline and at 3 months follow-up. RESULTS: At baseline and at 3 months, there were no differences between the compliance device group and the usual care group in self-care behaviors, pill counts, 6-minute walk-test distance, or Functional Class. However, quality of life improved significantly from baseline to 3-month follow-up (ANOVA, P =.006). This difference was due to an improvement in quality of life for the monitor group (P =.002) but not the usual care only group (P =.113). Patients in the compliance device group had a 94% medication compliance rate, 81% compliance with daily blood pressure monitoring, and 85% compliance with daily weight monitoring as compared to 51% for blood pressure monitoring and 79% for weight monitoring in the usual care group (P = NS). CONCLUSION: These are promising pilot results that, if replicated in a larger sample, may significantly improve care and outcomes for patients with heart failure.

Antifailure therapy including spironolactone improves left ventricular energy supply-demand relations in nonischemic dilated cardiomyopathy.

BACKGROUND: Left ventricular (LV) energy supply-demand imbalance is postulated to cause "energy starvation" and contribute to heart failure (HF) in nonischemic dilated cardiomyopathy (NIDCM). Using cardiac magnetic resonance (CMR) and [(11)C] acetate positron emission tomography (PET), we evaluated LV perfusion and oxidative metabolism in NIDCM and the effects of spironolactone on LV supply-demand relations. METHODS AND RESULTS: Twelve patients with NIDCM underwent CMR and PET at baseline and after ≥6 months of spironolactone therapy added to a standard HF regimen. The myocardial perfusion reserve index (MPRI) was calculated after gadolinium injection during adenosine, as compared to rest. The monoexponential clearance rate of [(11)C] acetate (kmono) was used to calculate the work metabolic index (WMI), an index of LV mechanical efficiency, and kmono/RPP (rate-pressure product), an index of energy supply/demand. At baseline, the subendocardium was hypoperfused versus the subepicardium (median MPRI, 1.63 vs. 1.80; P<0.001), but improved to 1.80 (P<0.001) after spironolactone. The WMI increased (P=0.001), as did kmono/RPP (P=0.003). These improvements were associated with reverse remodeling, increased LV ejection fraction, and decreases in LV mass and systolic wall stress (all P<0.002). CONCLUSIONS: NIDCM is associated with subendocardial hypoperfusion and impaired myocardial oxidative metabolism, consistent with energy starvation. Antifailure therapy improves parameters of energy starvation and is associated with augmented LV performance. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov/ Unique identifier: ID NCT00574119.

High reproducibility of adenosine stress cardiac MR myocardial perfusion imaging in patients with non-ischaemic dilated cardiomyopathy.

OBJECTIVE: To evaluate the reproducibility of first-pass contrast-enhanced cardiac MR (CMR) myocardial perfusion imaging in patients with non-ischaemic dilated cardiomyopathy (NIDCM). DESIGN: Prospective observational study. SETTING: Single centre, tertiary care hospital. PARTICIPANTS: 6 outpatient participants with NIDCM. OUTCOME: Reproducibility of semiquantitative myocardial perfusion analysis by CMR. METHOD: 6 patients with NIDCM were studied twice using first-pass of contrast transit through the left ventricular (LV) myocardium with a saturation-recovery gradient echo sequence at rest and during adenosine-induced hyperaemia. The anterior wall was divided into endocardial (Endo) and epicardial (Epi) segments. The Myocardial Perfusion Index (MPI) was calculated as the myocardial signal augmentation rate normalised to the LV cavity rate. The Myocardial Perfusion Reserve Index (MPRI) was calculated as hyperaemic/resting MPI. RESULTS: Between study 1 and 2, median MPI was similar for resting Endo (0.076 vs 0.077), hyperaemic Endo (0.143 vs 0.143), resting Epi (0.073 vs 0.074), and hyperaemic Epi (0.135 vs 0.134). Median MPRI was similar for Endo (1.84 vs 1.87) and Epi (1.90 vs 2.00). Combining Endo and Epi MPI (N=12), there was excellent agreement between Study 1 and 2 for resting MPI (r=0.998, intraclass correlation coefficient (ICC) 0.998, coefficients of variation (CoV) 1.4%), hyperaemic MPI (r=0.979, ICC 0.963, CoV 3.3%) and MPRI (r=0.989, ICC 0.94, CoV 3.8%). CONCLUSIONS: Resting and hyperaemic myocardial perfusion using a normalised upslope analysis during adenosine CMR is a highly reproducible technique in patients with NIDCM. TRIAL REGISTRATION NUMBER: Clinical Trials.Gov ID NCT00574119.

Intravenous glial growth factor 2 (GGF2) isoform of neuregulin-1ß improves left ventricular function, gene and protein expression in rats after myocardial infarction.

AIMS: Recombinant Neuregulin (NRG)-1ß has multiple beneficial effects on cardiac myocytes in culture, and has potential as a clinical therapy for heart failure (HF). A number of factors may influence the effect of NRG-1ß on cardiac function via ErbB receptor coupling and expression. We examined the effect of the NRG-1ß isoform, glial growth factor 2 (GGF2), in rats with myocardial infarction (MI) and determined the impact of high-fat diet as well as chronicity of disease on GGF2 induced improvement in left ventricular systolic function. Potential mechanisms for GGF2 effects on the remote myocardium were explored using microarray and proteomic analysis. METHODS AND RESULTS: Rats with MI were randomized to receive vehicle, 0.625 mg/kg, or 3.25 mg/kg GGF2 in the presence and absence of high-fat feeding beginning at day 7 post-MI and continuing for 4 weeks. Residual left ventricular (LV) function was improved in both of the GGF2 treatment groups compared with the vehicle treated MI group at 4 weeks of treatment as assessed by echocardiography. High-fat diet did not prevent the effects of high dose GGF2. In experiments where treatment was delayed until 8 weeks after MI, high but not low dose GGF2 treatment was associated with improved systolic function. mRNA and protein expression analysis of remote left ventricular tissue revealed a number of changes in myocardial gene and protein expression altered by MI that were normalized by GGF2 treatment, many of which are involved in energy production. CONCLUSIONS: This study demonstrates that in rats with MI induced systolic dysfunction, GGF2 treatment improves cardiac function. There are differences in sensitivity of the myocardium to GGF2 effects when administered early vs. late post-MI that may be important to consider in the development of GGF2 in humans.

Cell tracking and the development of cell-based therapies: a view from the Cardiovascular Cell Therapy Research Network.

Cell-based therapies are being developed for myocardial infarction (MI) and its consequences (e.g., heart failure) as well as refractory angina and critical limb ischemia. The promising results obtained in preclinical studies led to the translation of this strategy to clinical studies. To date, the initial results have been mixed: some studies showed benefit, whereas in others, no benefit was observed. There is a growing consensus among the scientific community that a better understanding of the fate of transplanted cells (e.g., cell homing and viability over time) will be critical for the long-term success of these strategies and that future studies should include an assessment of cell homing, engraftment, and fate as an integral part of the trial design. In this review, different imaging methods and technologies are discussed within the framework of the physiological answers that the imaging strategies can provide, with a special focus on the inherent regulatory issues.

Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction.

OBJECTIVES: This study sought to examine the effects of vasopressin V2 receptor antagonism with tolvaptan on the changes in left ventricular (LV) volumes over time. BACKGROUND: Vasopressin levels may be increased in patients with heart failure (HF) and may be a factor driving the progression of HF. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the effect of long-term administration of the vasopressin V2-receptor antagonist tolvaptan (30 mg/day) on reducing left ventricular end-diastolic volume (LVEDV) compared with placebo in patients with HF and reduced systolic function, using quantitative radionuclide ventriculography at baseline, repeated after 1 year of therapy, and repeated again approximately 1 week after withdrawal of study drug. RESULTS: A total of 120 patients were randomized to tolvaptan and 120 were randomized to placebo. In the placebo group, there was no change in LVEDV over the course of follow-up (change of 0.0 +/- 10.0 ml/m2). After 1 year of tolvaptan, there was a small reduction in LV volume (decrease of 1.8 +/- 10.7 ml/m2); the between-group difference was not significant (p = 0.21). During the course of the trial, there were 6 deaths (5%) and 21 HF hospitalizations (18%) in the tolvaptan group, compared with 11 deaths (9%) and 34 HF hospitalizations (28%) in the placebo group. In a time-to-event analysis, there was a significant favorable effect of tolvaptan on the composite of mortality or heart failure hospitalization (p < 0.03 by log-rank test). CONCLUSIONS: In a well-treated population of stable HF patients, there was no significant effect of tolvaptan therapy on LV volumes observed during 1 year of therapy. Nonprespecified natural history data favored therapy with tolvaptan, with a reduction in the combined end point of mortality and heart failure hospitalization observed. (Multicenter, Randomized, Double-Blind, Placebo Controlled, Efficacy Study on the Effects of Tolvaptan on Left Ventricular Dilatation in Congestive Heart Failure Patients; http://clinicaltrials.gov/ct/show/NCT00043758?order=1; NCT00043758).

Detection of carotid stenosis in African Americans with ischemic heart disease.

OBJECTIVES: This study was conducted to define the frequency of internal carotid stenosis in African American patients with ischemic heart disease (IHD). METHODS: We recruited 101 African American patients with IHD from a university medical center for carotid duplex examination. RESULTS: The frequency of >30%, >50%, and >70% stenosis was 21%, 11%, and 5%, respectively. Age >60 years (21% vs 3%, P < .01) and diabetes mellitus (22% vs 5%, P < .01) were predictors of unilateral stenosis of >50% and remained significant on multivariate testing. CONCLUSION: African American patients with established IHD have higher rates of extracranial carotid stenosis than community dwelling African American subjects and comparable rates with other populations.