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Biomedical subjects

W C Roberts

Publications and source records attributed to W C Roberts.

At least 235 records · Page 13Linked to original sources

Usefulness of total 12-lead QRS voltage compared with other criteria for determining left ventricular hypertrophy in hypertrophic cardiomyopathy: analysis of 57 patients studied at necropsy.

PURPOSE: The sensitivity of electrocardiographic indicators of left ventricular (LV) hypertrophy is known to be rather poor. To date, no study has undertaken a comparison of the various electrocardiographic criteria for LV hypertrophy among patients with hypertrophic cardiomyopathy (HC). In this study, we compared the sensitivity of the total 12-lead QRS amplitude with the sensitivity of certain standard electrocardiographic criteria for LV hypertrophy in necropsy patients with HC. MATERIALS AND METHODS: A total of 57 hearts were studied. The last technically satisfactory electrocardiogram available from each necropsy patient was used. Electrocardiographic criteria employed to diagnose LV hypertrophy included the Sokolow and Lyon index, the Romhilt-Estes voltage criteria, the Romhilt-Estes point score, the ratio of RV6:RV5 greater than 1 proposed by Holt and Spodick, and a method utilizing the sum of the amplitudes of the QRS complexes of all 12 leads. RESULTS: The total 12-lead QRS amplitude ranged from 66 to 339 mm (mean: 197 mm) (10 mm = 1 mV). Using 175 mm as the upper limit of normal, this technique yielded a sensitivity of 53%, which was the highest sensitivity of any criteria tested. The Sokolow-Lyon index had a sensitivity of 39%; the Romhilt-Estes voltage criteria, 37%; the Romhilt-Estes point score system, 49%; and the criterion of RV6 more than RV5, 39%. No correlation was found between total 12-lead QRS voltage and heart weight, LV free wall thickness, LV peak systolic and end-diastolic pressures, or LV outflow tract peak systolic pressure gradient. The 10 patients (18%) with transmural LV scars had significantly lower total 12-lead QRS voltage than did the 48 patients (78%) without such scars (155 mm versus 205 mm, p = 0.02). CONCLUSION: Total 12-lead QRS amplitude more than 175 mm is a useful indicator of LV hypertrophy and, among patients with HC, it is more sensitive than other more commonly employed criteria.

Adolescent↗

Safety of fenofibrate--US and worldwide experience.

Fenofibrate is a fibric acid derivative with enhanced potency and specificity of action on lipids. Preclinical toxicology reveals minimal toxic effects; dose-related changes occurred seldom, with only hepatic effects in rodents (mainly enzyme changes), some renal effects in dogs, and no reactions in monkeys. Teratogenicity tests were negative, and mutagenicity was not associated with fenofibrate. Carcinogenicity was evident in rodents with liver carcinoma at doses of 12 or 40 times the human dose, but cancer has not been associated with fenofibrate in over 10 years of clinical research and use. European experience with fenofibrate involved 7,145 patients in short- and long-term clinical trials, plus 10 years of marketing experience with a patient exposure of 6 million patient-years. Adverse effects were relatively low in frequency (6%) in the European clinical trials and manifested as gastrointestinal effects, muscle pain, skin problems, and sweating or dizziness. Short- and long-term fenofibrate studies revealed basically the same scope and frequency of adverse effects. Experience in US clinical trials mirrored the European experience; three types of adverse effects occurred more commonly in fenofibrate patients versus placebo: skin reactions, neurologic effects, and musculoskeletal reactions. Laboratory tests were mildly abnormal for liver function, leukocytes, and hemoglobin; these reactions were significant enough to be considered adverse drug experiences only occasionally. Hepatobiliary tests for lithogenicity showed an increase in cholesterol saturation, but gallstones seldom have been associated with fenofibrate. Postmarketing, open experiences in Europe over 10 years have been consistent with the study results. The rate of reactions has been low (about 115/year or a 0.3% incidence rate). The reactions noted in these spontaneous reports were hepatic, renal, gallstones, cutaneous, hematologic, sexual asthenia, and weight loss. In general, fenofibrate can be considered a safe and well-tolerated lipid-lowering drug that has been scrutinized extensively for safety in clinical research and during an already long marketing period in Europe.

Clinical Trials as Topic↗

Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronary arteries in acute myocardial infarction and in sudden coronary death.

We studied at necropsy atherosclerotic plaque composition in the four major (right, left main, left anterior descending, and left circumflex) epicardial coronary arteries in 15 patients who died of consequences of an acute myocardial infarction (AMI) and in 12 patients with sudden coronary death (SCD) without AMI. The coronary epicardial arteries were sectioned at 5-mm intervals, and a Movat-stained section of each segment of artery was prepared and analyzed using a computerized morphometry system. Within the AMI group and within the SCD group, there were no differences in plaque composition among any of the four major epicardial coronary arteries. Within both groups, plaque morphology varied as a function of cross-sectional-area narrowing of the segments. In both groups, the amount of dense relatively acellular fibrous tissue, calcified tissue, and pultaceous debris (amorphous debris containing cholesterol clefts, presumably rich in extracellular lipid) increased in a linear fashion with increasing degrees of cross-sectional-area narrowing of the segments, and the amount of cellular fibrous tissue decreased linearly. In the AMI group, the percentage of plaque consisting of pultaceous debris and of cellular fibrous tissue separated significantly narrowed (greater than 75% cross-sectional area) segments from less narrowed (less than 75%) segments. A comparison of the AMI group to the SCD group showed significant differences. The percentage of plaque consisting of pultaceous debris (16% in the AMI group and 7% in the SCD group), of cellular fibrous tissue (11% vs. 18%), and of heavily calcified tissue (8% vs. 16%) were significantly different in the severely narrowed segments in the AMI and SCD groups. When all arteries containing thrombi were deleted from the analysis, there were no significant changes in the results. Occlusive coronary thrombi were present in 13 of the 15 AMI patients and in one of the 12 SCD patients. Thus, the frequency of coronary thrombi and plaque composition differ in patients with AMI and in those with SCD without AMI.

Coronary Artery Disease↗

Anomalous origin of either the right or left main coronary artery from the aorta without coursing of the anomalistically arising artery between aorta and pulmonary trunk.

Clinical and necropsy findings are described in 12 adults (10 men) in whom either the left main coronary artery or the right coronary artery arose abnormally from the aorta and the anomalistically arising artery coursed thereafter either normally or abnormally, but if abnormally not between the pulmonary trunk and ascending aorta. None of the 12 patients had symptoms of myocardial ischemia that unequivocally could be attributed to the anomalously arising coronary artery. One patient, a 19-year-old man, however, died suddenly and no abnormality other than the anomalistically arising right coronary artery from the posterior aortic valve sinus was found.

Adult↗

Calcium channel binding characteristics in the human heart.

The number, affinity, pharmacologic specificity and regional distribution of calcium channel binding sites in human hearts obtained at autopsy and open heart surgery were characterized using the radioligand [3H]nitrendipine. Scatchard analyses of saturation data from 6 autopsy hearts revealed a homogeneous distribution of high affinity binding sites (affinity-1 [KD] = 0.44 +/- 0.06, 0.52 +/- 0.07, 0.32 +/- 0.02, 0.30 +/- 0.03, and 0.45 +/- 0.01 nM; binding capacity [Bmax] = 30 +/- 4, 27 +/- 6, 25 +/- 7, 33 +/- 3, and 28 +/- 4 fmol/mg protein in right atrium, right ventricle, left atrium, left ventricle and ventricular septum, respectively). In ligand competition experiments, nifedipine and nitrendipine completely displaced binding with partial displacement by verapamil and 35% enhancement of binding by 10(-5) M diltiazem at 37 degrees. Analyses of right atrial appendages obtained at open heart surgery from 5 coronary artery bypass patients provided similar results (KD = 0.2 +/- 0.03 nM, Bmax = 42 +/- 2 fmol/mg protein). In addition, no significant differences in KD or Bmax were found in 3 hamster hearts assayed at the time of death or up to 18 hours postmortem at either 4 or 25 degrees. In contrast, there was a significant increase in Bmax (110 fmol/mg protein) with no change in KD (0.3 nM) in a myomectomy specimen from a patient with obstructive hypertrophic cardiomyopathy compared with either autopsy or surgical specimens. These studies illustrate the feasibility and potential advantages of studying calcium channels directly in human hearts.

Adult↗

Location of an acute myocardial infarct in patients with a healed myocardial infarct: analysis of 129 patients studied at necropsy.

To determine the relation of a single healed myocardial infarct to a fatal acute myocardial infarct, 129 patients with 1 grossly visible healed and 1 grossly visible acute infarct were studied at necropsy. It was determined whether the acute infarct was opposite to or adjacent to the healed infarct or if 1 infarct was so large that it was both opposite to and adjacent to the other infarct. In 74 (57%) of the 129 patients, the 2 infarcts were opposite one another, in 40 (31%) they were adjacent and in 15 (12%) they were both opposite and adjacent. The age, sex, mean size of the healed infarct and heart weight were similar among the 3 groups. Acute myocardial infarcts were larger in the group that had both opposite and adjacent infarcts than either of the other 2 groups (p less than 0.001). Information regarding whether the infarcts were clinically recognized or not was available in 108 patients: both infarcts were recognized in 41 (38%), neither infarct was recognized in 15 (14%) and 1 infarct was recognized and the other was not in 52 (48%). The number of the 4 major epicardial coronary arteries narrowed at some point greater than 75% in cross-sectional area by atherosclerotic plaque was similar in patients with recognized and in those with unrecognized infarcts. Similar numbers of narrowed major epicardial coronary arteries also were found in each of the 3 infarct groups (opposite, adjacent or both).

Acute Disease↗

Rupture of the left ventricular free wall during acute myocardial infarction: analysis of 138 necropsy patients and comparison with 50 necropsy patients with acute myocardial infarction without rupture.

Clinical and necropsy findings in 138 patients (69 men and 69 women) with rupture of the left ventricular (LV) free wall during acute myocardial infarction (AMI) (rupture group) were compared with 50 patients who died during their first AMI without rupture (nonrupture group). The frequency of systemic hypertension (55 vs 52%), angina pectoris (13 vs 22%) and congestive heart failure (0 vs 0%) before the fatal AMI was similar for both rupture and nonrupture groups. Mean heart weights for men (479 vs 526 g) and women (399 vs 432 g) with and without rupture also were insignificantly different. LV scar before the infarct that ruptured was present in 18 patients (13%); previous necropsy studies of fatal AMI without rupture have indicated that 50% have LV scars. The rupture group had a significantly more frequent (p less than 0.01) lateral wall location of the infarct (12 vs 2%). The number of 3 major (right, left anterior descending and left circumflex) epicardial coronary arteries narrowed at some point greater than 75% in cross-sectional area by atherosclerotic plaque was significantly lower (p less than 0.01) in the rupture group (39 vs 58%). The percent of these 3 arteries totally occluded or nearly so (greater than 95% in cross-sectional area) by plaque also was significantly less (p less than 0.001) in the rupture group (24 of 198 arteries [12%] vs 38 of 144 arteries [26%]). Analysis of each 5-mm long segment of these arteries in each group disclosed that the rupture group had significantly less narrowing than the nonrupture group. Of the 3,287 five-mm segments of artery examined in the rupture group (66 patients), 512 (15%) were narrowed greater than 75% in cross-sectional area by plaque; in contrast, of the 1,848 five-mm segments in the nonrupture group (38 patients), 508 (28%) were narrowed to this degree by plaque (p less than 0.0001). Thus, rupture of the LV free wall primarily is a complication of the first AMI and is associated with considerably less amounts of coronary narrowing than fatal AMI without rupture.

Aged↗

Anomalous origin of either the right or left main coronary artery from the aorta with subsequent coursing between aorta and pulmonary trunk: analysis of 32 necropsy cases.

Anomalous origin of either the left main coronary artery (LMCA) or right coronary artery (RCA) from the aorta with subsequent coursing between the aorta and pulmonary trunk is a rare and sometimes fatal coronary artery anomaly. Thirty-two cases of these anomalies were reviewed, with particular attention to the exact location and shape of the anomalistically positioned ostium and coronary dominance. The LMCA (7 cases) arose either from behind the right coronary sinus (6 cases) or as a single ostium with the RCA straddling the right-left commissure and right coronary sinus (1 case). In 5 of the 7 cases, the anomaly was fatal. In 6 cases of anomalous origin of the LMCA, the RCA was dominant and in 4 the anomaly was fatal. In only 1 case of anomalous origin of the LMCA was the left circumflex coronary artery dominant, and in this case the anomaly also was fatal. The RCA (25 cases) arose either from behind the left coronary sinus (8 cases), above the left coronary sinus (5 cases), from above the right-left commissure (10 cases) or as a single ostium with the LMCA above the right-left commissure and left coronary sinus (2 cases). In 8 of these 25 cases the anomaly was fatal. In 7 cases of anomalous origin of the RCA, the left circumflex coronary artery was dominant and in no case was the anomaly clinically significant. In 1 case, both the RCA and left circumflex coronary artery were hypoplastic and the anomaly was fatal. Coronary dominance, not ostial shape, was useful in separating the clinically significant from the clinically insignificant anomalies.

Adolescent↗

Frequency of myocarditis, left ventricular dysfunction and ventricular tachycardia in the acquired immune deficiency syndrome.

To evaluate possible relations between clinical and histopathologic cardiac findings in patients with the acquired immune deficiency syndrome (AIDS), 58 consecutively autopsied AIDS patients were reviewed retrospectively. Twenty-six (45%) had histopathologic myocarditis. Fifteen of these 26 (58%) had greater than or equal to 1 clinical cardiac abnormalities: 6 had congestive heart failure or left ventricular (LV) dysfunction, or both, 4 had ventricular tachycardia (VT), 10 had electrocardiographic abnormalities and 4 had pericardial abnormalities. Of the 32 patients without myocarditis, 6 (19%) had pericardial or electrocardiographic abnormalities, or both, but none had congestive heart failure, LV dysfunction or VT. Overall, clinical cardiac abnormalities were found in 21 patients (36%). Patients with myocarditis had a significantly higher incidence of clinical cardiac abnormalities than patients without myocarditis (58 vs 19%, p less than 0.01). All patients with congestive heart failure, LV dysfunction or VT had myocarditis. Thus, serious clinical cardiac abnormalities were common in patients with AIDS and were associated with myocarditis.

Acquired Immunodeficiency Syndrome↗