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Many factors enter into the decision by the Food and Drug Administration (FDA) to approve a new drug for use by physicians and other health care providers in treating diseases. Initially, the FDA authority was restricted to issues of safety and only later did the documentation of efficacy become part of the review process required for approval. However, all drugs have the potential for causing harm at some dose level to all and at lower doses in certain patients with vulnerability to the particular pharmacology of the agent. As new drugs have been designed to manage disorders that are uncommon, but of significant consequence, they may have adverse effects that are acceptable only because they are so uniquely beneficial to these specific conditions. The risk of these adverse effects may be acceptable since the benefit can outweigh the harm in most patients and the adversity can be predicted and managed. The approval of this category of drugs has grown rapidly since definition of a mechanism of action to manage and modify the risk has been provided by a process known as known as Risk Evaluation and Mitigation Strategy or "REMS." In 2007, the Food and Drug Administration Amendments Act (FDAAA) allowed the FDA to require postmarketing studies and the authority to mandate the implementation of a REMS for drugs with efficacy but documented potential for harm. Two relatively new drugs useful in the management of severe elevations of low-density lipoprotein cholesterol have been approved under a requirement for a REMS. These are lomitapide, an inhibitor of microsomal triglyceride transfer protein and mipomersen, an antisense oligonucleotide which reduces the synthesis of apolipoprotein B., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

This retrospective study, conducted as part of a private practice quality assurance process for patients with coronary artery disease (CAD), compares practice patterns in the LIFEHELP lipid clinic and non-lipid clinic settings at the Heart Institute of St. Petersburg. Quality assurance parameters included documentation of low-density lipoprotein (LDL) cholesterol, initiation of lipid-lowering therapy, and achievement of the Second National Cholesterol Education Program (NCEP II) goal for CAD patients of LDL cholesterol < or =100 mg/dL. A total of 934 patient charts with ICD-9 codes of 410-414 for ischemic heart disease were randomly selected and reviewed by a utilization review nurse. A higher level of documentation and treatment of elevated LDL cholesterol to NCEP II goal in CAD patients was found for those followed in the lipid clinic. Among non-lipid clinic physicians, cardiologists documented and treated elevated LDL cholesterol more frequently than primary care physicians. Women and the elderly subgroups received improved care in the lipid clinic setting. Screening activities and risk-factor management by cardiologists within a lipid clinic, therefore, demonstrated an improved standard of care that came closer to achieving national guidelines in the secondary prevention of CAD.

Seven subjects with rate-dependent left bundle branch block (RDLBBB) and 13 subjects with normal conduction (control group) underwent upright bicycle exercise radionuclide angiography to determine the effects of the development of RDLBBB on global and regional left ventricular function. Six of the seven subjects with RDLBBB had atypical chest pain syndromes; none had evidence of cardiac disease based on clinical examination and either normal cardiac catheterization or exercise thallium-201 scintigraphy. Radionuclide angiograms were recorded at rest and immediately before and after RDLBBB in the test group, and at rest and during intermediate and maximal exercise in the control group. The development of RDLBBB was associated with an abrupt decrease in left ventricular ejection fraction (LVEF) in six of seven patients (mean decrease 6 +/- 5%) and no overall increase in LVEF between rest and maximal exercise (65 +/- 9% and 65 +/- 12%, respectively). In contrast, LVEF in the control group was 62 +/- 8% at rest and increased to 72 +/- 8% at intermediate and 78 +/- 7% at maximal exercise. The onset of RDLBBB was associated with the development of asynchronous left ventricular contraction in each patient and hypokinesis in four of seven patients. All patients in the control group had normal wall motion at rest and exercise. These data indicate that the development of RDLBBB is associated with changes in global and regional ventricular function that may be confused with development of left ventricular ischemia during exercise.

Histologic pictures have been conflicting in previous cases of quinidine-associated hepatitis. We report a case of reversible granulomatous hepatitis from quinidine hypersensitivity, with granuloma induction occurring within three days after readministration of quinidine. Fever, urticaria, and mild thrombocytopenia were associated clinical findings. Both light and electron microscopic study results are reported.

Aneurysm formation in saphenous vein aortocoronary bypass grafts is an extremely rare complication of coronary artery bypass surgery. Aneurysms of native coronary arteries are found in a small percentage of patients at autopsy. Reported is a case with multiple coronary artery aneurysms in which a dissecting aneurysm of the saphenous vein bypass graft also developed following coronary artery bypass surgery. This is the first report of such association.

Myocardial infarct extension, defined as reelevation or reappearance of creatine phosphokinase-MB (CK-MB) 48 hours after the onset of symptoms, was evaluated prospectively in 56 consecutive patients with acute myocardial infarction. Myocardial infarct extension occurred in eight patients (14%). The sensitivity, specificity and predictive accuracy in the diagnosis of myocardial infarct extension were 63%, 85% and 42%, respectively, for recurrent chest pain requiring morphine; 50%, 65% and 19% for recurrent ST-segment elevation on routine 12-lead ECGs; and 88%, 63% and 28% for reelevation of total CK. Three of the eight episodes of extension were clinically silent. Four of eight patients (50%) with extension died, compared with one of 46 patients (2%) without extension (p = 0.0009). CK-MB persisted for 72 hours or longer in 16 patients and identified seven of eight patients who subsequently had infarct extension. We conclude that myocardial infarct extension is an infrequent complication of acute myocardial infarction and is associated with a very high mortality rate. Persistence of CK-MB for 72 hours or more identifies a subgroup of patients at high risk for subsequent infarct extension and death.

Congenital aneurysm of the left atrial appendage is a rare anomaly, usually presenting in adult life. The case reported is that of a 55-year-old man who died of cerebral embolism originating from a thrombus in a congenital aneurysm of the left atrial appendage. The cardiac silhouette 11 years previously had suggested a cardiac tumour or a pericardial cyst. As judged frm 14 published cases, the major manifestations of these aneurysms are an abnormal cardiac silhouette in the x-ray, supraventricular tachycardia, and systemic embolism. Angiocardiography appears to be the method of choice in establishing the diagnosis. Resection of th aneurysm is the recommended form of treatment.

This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.