Comprehensive approach to cardiac amyloidosis care: considerations in starting an amyloidosis program

Heart Failure Reviews - Amyloidosis is a multisystem disease which continues to present in later stages due to delayed diagnosis. Once the disease is identified, the coordination of ongoing care...     

Electrocardiographic changes associated with β-blocker toxicity

Study objective: We sought to characterize the ECG changes associated with symptomatic β-blocker overdose. Methods: The study population consisted of a prospective cohort of patients reporting to 2 regional poison centers with β-blocker overdose. Each patient received an ECG on presentation and a structured follow-up. The inclusion criteria for symptomatic overdose included heart rate of less than 60 beats/min or systolic blood pressure of less than 90 mm Hg; symptoms consistent with decreased end-organ perfusion; therapeutic intervention with cardioactive medication; and corroboration by 2 of the authors that this was a clear-cut case of symptomatic β-blocker overdose with cardiovascular toxicity. Exclusion criteria included cardioactive coingestants, age younger than 6 years, and no available ECG. Results: Of 167 patients, 13 were determined to have symptomatic exposures. First-degree heart block (>200 ms) was the most common ECG finding (10/12) and also had the greatest likelihood ratio (5.31) when comparing those with symptomatic exposures with those with asymptomatic exposures. Comparing the asymptomatic with the symptomatic groups, the mean PR interval was 167 ms (95% confidence interval [CI] 162 to 171 ms) versus 216 ms (95% CI 193 to 238 ms), the mean QRS interval was 89 ms (95% CI 87 to 91 ms) versus 112 ms (95% CI 92 to 132 ms), the mean QTc interval was 422 ms (95% CI 417 to 428) versus 462 ms (95% CI 434 to 490 ms), and the mean heart rate was 72 beats/min (95% CI 69 to 74 beats/min) versus 66 beats/min (95% CI 59 to 73 beats/min). Two cases of symptomatic acebutolol exposure appeared unique by demonstrating disproportionate prolongation of the QTc interval, an RaVR height of 3 mm or greater, and associated ventricular tachydysrhythmia. Conclusion: The majority of clinically significant β-blocker intoxications demonstrate negative dromotropic effects on ECG. Several ECG differences in acebutolol intoxication might reflect unique pathophysiologic processes relative to other β-blockers. [Ann Emerg Med. 2002;40:603-610.]     

Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound

OBJECTIVES: The aim of this study was to evaluate the feasibility and the ability of intravascular optical coherence tomography (OCT) to visualize the components of coronary plaques in living patients. BACKGROUND: Disruption of a vulnerable coronary plaque with subsequent thrombosis is currently recognized as the primary mechanism for acute myocardial infarction. Although such plaques are considered to have a thin fibrous cap overlying a lipid pool, imaging modalities in current clinical practice do not have sufficient resolution to identify thin (< 65 microm) fibrous caps. Optical coherence tomography is a new imaging modality capable of obtaining cross-sectional images of coronary vessels at a resolution of approximately 10 microm. METHODS: The OCT images and corresponding histology of 42 coronary plaques were compared to establish OCT criteria for different types of plaques. Atherosclerotic lesions with mild to moderate stenosis were identified on angiograms in 10 patients undergoing cardiac catheterization. Optical coherence tomography and intravascular ultrasound (IVUS) images of these sites were obtained in all patients without complication. RESULTS: Comparison between OCT and histology demonstrated that lipid-rich plaques and fibrous plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs obtained from patients were compared. Axial resolution measured 13 +/- 3 microm with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications and echolucent regions identified by IVUS were visualized in corresponding OCT images. Intimal hyperplasia and echolucent regions, which may correspond to lipid pools, were identified more frequently by OCT than by IVUS. CONCLUSIONS: Intracoronary OCT appears to be feasible and safe. Optical coherence tomography identified most architectural features detected by IVUS and may provide additional detailed structural information.     

The hemorheological effects of raloxifene in postmenopausal women with osteoporosis. Results of a 3-year placebo-controlled clinical trial

Raloxifene, the prototype of the selective estrogen receptor modulators, has been associated with an increased risk of venous thromboembolism. As hemorheological factors may be involved in thrombus formation this placebo-controlled study investigated whether raloxifene was associated with changes in determinants of blood viscosity. Fifty-seven post-menopausal women were randomly assigned to receive placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day for 36 months. Venous blood samples were collected at baseline and at 12-monthly intervals and used to measure hematocrit, whole blood and plasma viscosity and plasma fibrinogen concentration. Time- and treatment-related changes in the grouped and pooled data was analysed using ANOVA with repeated measures and correlation matrices. The mean values of all the hemorheological indices showed small inconsistent changes within the normal reference range over the 36-month period of the study. There was a small but significant decrease over time in high shear rate blood viscosity and plasma viscosity in raloxifene-treated subjects compared to those receiving placebo (p<0.05). Correlation analyses showed the anticipated relationships between blood viscosity and hematocrit and plasma viscosity levels and also between plasma viscosity and plasma fibrinogen concentration. No subject developed a thromboembolic vascular event during the study. These results show that compared with placebo treated-subjects, long-term raloxifene treatment in post-menopausal women, at a dose of either 60 or 120 mg daily, was not associated with adverse changes in hemorheological factors that may contribute to venous thromboembolism.     

Oral treatment with an antioxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with Type II diabetes

Aims/hypothesis. To determine whether raxofelast, a new water soluble antioxidant decreases oxidative stress and improves endothelial function in men with Type II (non-insulin dependent) diabetes mellitus. Methods. We treated ten normotensive, normocholesterolaemic men with Type II diabetes and as controls ten healthy men matched with them for age with raxofelast (600 mg twice daily) for 1 week. Plasma 8-epi-PGF₂α, a non-enzymic oxidation product of arachidonic acid was measured by gas chromatography/mass spectrometry as an index of oxidative stress. Forearm vasodilator responses to brachial artery infusion of acetylcholine (7.5, 15 and 30 μg min^–1) and of the nitric oxide donor nitroprusside (1, 3 and 10 μg min^–1) were measured by strain gauge plethysmography. Results. Plasma concentrations of 8-epi-PGF₂α were greater in diabetic than in control men (0.99 ± 0.20 vs 0.18 ± 0.01 nmol l^–1, means ± SEM, p < 0.001) and fell after raxofelast (from 0.99 ± 0.20 to 0.47 ± 0.07 nmol l^–1, p < 0.05) in diabetic men but not in control men. Blood flow responses to acetylcholine were lower (p < 0.05) in diabetic than in control men (7.4 ± 1.0 vs 12.9 ± 2.3 ml · min^–1· 100 ml^–1 for the highest dose). In diabetic men, but not in control men, raxofelast increased (p < 0.05) blood flow responses to acetylcholine (from 7.4 ± 1.0 ml · min^–1· 100 ml^–1 to 11.3 ± 2.3 ml · min^–1· 100 ml^–1 at highest dose). Blood flow responses to nitroprusside were similar in control and diabetic men and in both groups were similar before and after raxofelast. Conclusion/interpretation. Oral treatment with raxofelast for 1 week reduces oxidative stress and improves endothelial function in men with Type II diabetes. [Diabetologia (2000) 43: 974–977] Received: 14 October 1999 and in revised form: 28 May 2000     

Linking components of event-related potentials and autonomic measures of the orienting reflex

This study examined autonomic measures and event-related potentials (ERPs) associated with elicitation and habituation of the basic Orienting Reflex (OR). Subjects received 16 innocuous tones with intensity alternating between 60 and 80 dB, at long inter-stimulus intervals. There was no stimulus-related task, so we could examine the effects of stimulus novelty and intensity in the absence of task demands. Cardiac, respiratory, peripheral vasoconstriction, and electrodermal measures were recorded, as well as continuous EEG. Single-trial ERPs were obtained, and components extracted by Principal Components Analysis were examined for potential response fractionation in the central indices of stimulus processing. The predicted fractionation of autonomic measures was obtained: cardiac deceleration showed no systematic change with intensity or trials, respiratory pause showed a substantial main effect of trials but no intensity effects, peripheral vasoconstriction showed intensity but no trials effects, and electrodermal responses showed substantial main effects of trials and intensity. A range of intensity and novelty effects were obtained in components identified as the N1, P3a, P3b, Novelty P3, and the classic Slow Wave. The different stimulus–response profiles of the ERP components are discussed in relation to the autonomic response profiles within the context of a sequential processing theory of OR elicitation.