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Background Increased low-density lipoprotein (LDL) and oxidized LDL cholesterol levels adversely affect endothelial function in patients with stable coronary artery disease (CAD). Statin drugs are efficacious in primary and secondary prevention of clinical CAD events, but they have not been extensively studied as a treatment for ischemia during routine daily activities or during exercise, indicators of high-risk in patients with stable CAD. The purpose of the Vascular Basis for the Treatment of Myocardial Ischemia study is to determine whether aggressive lowering of LDL cholesterol level with atorvastatin, with or without supplemental antioxidant vitamins C and E, can improve endothelial function and ischemia during ambulatory electrocardiogram (AECG) monitoring and exercise treadmill testing (ETT). Methods Patients are eligible when they have ischemia during an ETT and AECG monitoring and when their fasting total cholesterol level is ≤250 mg/dL. Eligible patients are randomized to receive 1 of 3 treatments: intensive atorvastatin to reduce LDL cholesterol level to ≤80 mg/dL, intensive atorvastatin to reduce LDL cholesterol level to ≤80 mg/dL plus antioxidant vitamins C and E, and control of diet and low-dose lovastatin, when needed, to reduce LDL cholesterol level ≤ to 130 mg/dL. Patients undergo endothelial function testing, 48-hour AECG monitoring, and ETT at randomization and at 6 and 12 months. Results A total of 300 patients have been randomized: 101 to receive atorvastatin alone, 103 to receive atorvastatin plus antioxidant vitamins, and 96 to receive placebo. Baseline characteristics are similar across treatment groups. Conclusions The Vascular Basis study will provide important insight on the effects of aggressive management of dyslipidemia with statin drugs and antioxidant vitamins in patients with stable but high-risk CAD.

Plasma lipoprotein levels, including remnant-like particle (RLP) cholesterol and RLP triglycerides, were assessed in fasting (12 hours) and postprandial (PP) (4 hours after a fat-rich meal) states in 88 patients with coronary heart disease (CHD) and 88 controls. All lipoproteins were assessed by direct methods. We hypothesized that patients with CHD would have greater percent increases in their triglyceride levels, RLP cholesterol, and RLP triglycerides, in response to a fat-rich meal. In the fasting state, triglycerides, RLP cholesterol, RLP triglycerides, and low-density lipoprotein (LDL) cholesterol levels were all significantly higher in cases versus controls by 51%, 35%, 39%, and 40%, respectively. These levels were 57%, 37%, 64%, and 37% higher in the PP state, respectively. Mean high-density lipoprotein (HDL) cholesterol values were 27% lower in cases in both the fasting and PP states. After eating, triglycerides, RLP cholesterol, and RLP triglycerides increased 64%, 71%, and 290% in controls, respectively, whereas in cases these levels increased by 71%, 94%, and 340%, respectively (all p

PURPOSE This randomized controlled study assessed whether adding a program of high-intensity strength training (80% of maximum) to an outpatient cardiac rehabilitation program would be a safe and effective means of improving muscle strength and body composition. METHODS Thirty-eight cardiac patient volunteers (29 men and 9 women) were randomized to either high-intensity strength training or flexibility training added concurrently to a 12-week outpatient cardiac rehabilitation aerobic exercise program. Muscle strength, local muscle endurance, joint flexibility, maximum treadmill tolerance time, and body composition were measured before and after completion of the training. RESULTS The strength-trained patients (n = 18) had greater increases in mean strength (90 +/- 19% versus 9 +/- 4%, P < 0.0001) and local muscle endurance (20 versus 6 times, P < 0.0001), and decreases in mean perceived exertion for lifting the initial one repetition maximum load (11 +/- 1 versus 15 +/- 1, P < 0.0001) when compared with flexibility-trained patients (n = 16). The strength group lost more body fat (2.8 +/- 2.0 versus 1.3 +/- 2.0 kg, P < 0.01), tended to gain more lean tissue (1.5 +/- 2.3 versus 0.5 +/- 1.2 kg, P < 0.10), and had greater improvements in treadmill time (2.3 +/- 1.3 versus 1.2 +/- 1.0 minute, P < 0.02) than did the flexibility group. Improvements in joint flexibility were similar for each group. None of the subjects had evidence of cardiac ischemia or arrhythmia during the training sessions. CONCLUSIONS Medically supervised high-intensity strength training is well tolerated when added to the aerobic training of cardiac rehabilitation programs and allows patients to aggressively gain the strength and endurance they will need to complete daily living tasks at lower perceived efforts. Strength training also reduces cardiac risk factors by improving body composition and maximum treadmill exercise time.

Cardiac rehabilitation programs have not consistently been shown to improve the psychological well being of their patients. In our study of 38 cardiac patients (29 men and 9 women), a variety of quality-of-life parameters were assessed before and after they completed either 12 weeks of high-intensity strength training or flexibility training added to their outpatient cardiac rehabilitation aerobic exercise program. The strength-trained patients increased their self-efficacy scores for lifting (29% vs 4%, p

An in vitro technique using color flow imaging and continuous wave Doppler was developed to measure the initial regurgitant flow jet diameter and velocity integral to yield the parameters for a volume calculation. Jets were produced by volume-controlled injection through tubes of various diameters (1.3, 1.9, 2.8, and 3.5 mm) to deliver volumes from 1 to 7 ml over 100 to 300 msec at pressures from 40 to 200 mm Hg. One hundred forty-five samples were obtained. Flow jet diameter consistently overestimated tube diameter by 2 mm when injected volume was 1.5 to 7 ml and by 1.5 mm when injected volume was less than 1.5 ml. This offset was stable with various transducers (2.5, 3.5, 5.0 MHz) at normal gain setting (just under noise). Therefore, corrected flow jet diameter (FJD) = FJD - 2 mm, and Doppler volume = corrected flow jet area x velocity integral. A range of injectates from 1.1 to 7 ml generated Doppler volume of 1.0 to 8.2 ml. The relation between Doppler volume (DV) and injected volume (IV) was DV = 1.079 IV - 0.22, r2 = 0.945, p less than 0.01. This relation was not altered by tube diameter. Thus a method combining color flow imaging and continuous wave Doppler provides a reliable and accurate measure of in vitro flow volume.

The effects of atorvastatin (40 mg/day) versus placebo on fasting and postprandial plasma levels of high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were examined over 36 weeks in 84 patients who had coronary heart disease and low-density lipoprotein cholesterol levels130 mg/dl and compared directly with the effects of fluvastatin, lovastatin, pravastatin, and simvastatin. Results were also compared with those obtained in age- and gender-matched control subjects (n = 84). Feeding increased median hs-CRP levels by 2% in patients (p = NS) and 22% in controls (p0.01) and increased mean Lp-PLA2 values by 9% in patients (p = NS) but decreased values by 21% in controls (p0.0001). Patients had 51% higher median hs-CRP values and 29% higher mean Lp-PLA2 values than did controls (p0.05 for hs-CRP and Lp-PLA2) in the fasting state; however, Lp-PLA2 values were 62% higher (p0.0001) in the fed state in patients compared with controls. Atorvastatin decreased median hs-CRP levels by 32% (p0.01) and mean Lp-PLA2 values by 26% in patients (p0.0001), with similar decreases in the fed state, and none of the other statins had any significant effect on these parameters. Change in Lp-PLA2 was significantly related to change in low-density lipoprotein cholesterol (p0.01), with no significant relations with change in hs-CRP. Our data indicate greater differences in patients with coronary heart disease compared with controls in Lp-PLA2 in the fed state than in the fasting state and that atorvastatin is more effective than fluvastatin, lovastatin, pravastatin, or simvastatin for decreasing not only low-density lipoprotein cholesterol but also hs-CRP and Lp-PLA2.

The effects of atorvastatin at 20, 40, and 80 mg/day on plasma lipoprotein subspecies were examined in a randomized, placebo-controlled fashion over 36 weeks in 97 patients with coronary heart disease (CHD) with low-density lipoprotein (LDL) cholesterol levels of >130 mg/dl and compared directly with the effects of fluvastatin (n = 28), pravastatin (n = 22), lovastatin (n = 24), and simvastatin (n = 25). The effects of placebo and 40 mg/day of each statin were also examined in subjects with CHD with subjects in the fasting state and in the fed state 4 hours after a meal rich in saturated fat and cholesterol and compared with results in age- and gender-matched control subjects. At all doses tested in the fasting and fed states, atorvastatin was significantly (p

The effects of atorvastatin at 20, 40, and 80 mg/day on plasma lipoprotein subclasses were examined in a randomized, placebo-controlled fashion over 24 weeks in 103 patients in the fasting state who had coronary heart disease (CHD) with low-density lipoprotein (LDL) cholesterol levels >130 mg/dl. The effects of placebo and atorvastatin 40 mg/day were examined in 88 subjects with CHD in the fasting state and 4 hours after a meal rich in saturated fat and cholesterol. These findings were compared with results in 88 age- and gender-matched control subjects. Treatment at the 20, 40, and 80 mg/day dose levels resulted in LDL cholesterol reductions of 38%, 46%, and 52% (all p

In patients with stable angina pectoris and evidence of myocardial ischemia, intensive therapy with atorvastatin was associated with a more rapid decline in CRP than low-dose lovastatin. In the atorvastatin group, half of the long-term decrease occurred within 4 weeks of intensive therapy. Intensive therapy with statins to reach low LDL targets (

The ability of the echocardiogram to define mitral valve opening and closure was assessed by simultaneously recording the echocardiogram of the anterior leaflet (ECHO) with intracardiac pressures, aortic second sound, and ECG on 38 occasions in 14 patients undergoing cardiac catheterization. Hemodynamic opening and closure were defined by intersection of the pulmonary wedge and left ventricular pressures and the onset of left ventricular systole. The onset of the most rapid anterior motion (D') in early diastole and termination of the last rapid posterior movement in end diastole (Co) were used as echocardiographic markers of mitral valve opening and closure. Intervals measured included: the isovolumic relaxation period (IRP) from A2 to either hemodynamic (IRPH) or echocardiographic (IRPE) opening; the Q to closure interval (QCI) from the Q wave to either hemodynamic (QCIH) or echocardiographic (QCIE) closure; and diastolic filling period (DFP), either hemodynamic (DFPH) or echocardiographic (DFPE). The following significant (P less than .01) regression equations resulted: IRPE equals (.97) IRPH plus 30 (sem plus or minus 8 msec) r equals .89; QCIE equals (.68) QCIH plus 37 (sem plus or minus 7 msec) r equals .71; DEPE equals (.98) DFPH plus 10 (sem plus or minus 18 msec) r equals .98. Thus hemodynamic markers of opening and closure systematically precede echocardiographic markers of opening (D') and closure (Co) and the diastolic filling periods are equal within 10 msec. It is concluded that the echocardiogram of the anterior leaflet is a reliable indicator of hemodynamic markers of opening and closure of the mitral valve in man and is useful in the noninvasive determination of certain systolic and diastolic time intervals.

Twenty-one patients with anomalous coronary artery origin from the aorta are discussed, and the cases reported in the literature are reviewed. The left anterior descending (LAD) and left circumflex (Cx) arteries arose aberrantly from the right sinus of Valsalva of the aorta (RSV) in six patients. In four of these patients the connecting branch from the anomalous origin passed anterior to the aorta and the right ventricular in-fundibulum (RVinf), and in two patients, this branch passed between the aorta and RVinf. In 11 patients only the Cx was aberrant, and arose either from the RSV directly or from the right coronary artery (RCA), and passed posterior to the aorta and RVinf. In four patients the RCA arose aberrantly — in three from the left sinus of Valsalva of the aorta passing anteriorly, and in one from the left Cx passing posteriorly. Aberrant coronary artery origin from the aorta had clinical consequences only when the branch connecting the LAD and Cx to the RSV passed between the aorta and RVinf. Both our findings and those reported in the literature associate this variant with exertional sudden death in young persons. Anomalous coronary patterns can be delineated readily by selective coronary cineangiography, and as illustrated, the right anterior oblique projection can readily distinguish those prone to sudden death from the clinically insignificant variants. The former can be corrected with coronary artery bypass surgery.

Lymph chylomicrons are at the lipid-rich end of the spectrum of the lipoproteins. The nature of their protein moiety and its biosynthesis have not yet been fully elucidated. Observations are reported on the incorporation of radioactive leucine into a "lowest density lipoprotein" by mucosal cells of the small intestine isolated from the rat during absorption of fat. The amino acid incorporation exhibited the characteristic energy requirement and sensitivity to inhibitors of other systems for biosynthesis of proteins. The protein moiety was not homogeneous, but appeared to consist of a small number of species that could be separated by thin layer electrophoresis in starch granules. Similar, but nonidentical, electrophoretic patterns were obtained with the residual soluble intracellular protein of the intestinal mucosa and with chylomicrons of intestinal lymph. The lowest density lipoprotein was isolated from a homogenate of the mucosal cells. After removal of lipids by extraction with organic solvents, the protein moiety exhibited several unusual properties in addition to its affinity for lipids: (a) a predominance of apolar amino acids, (b) resistance to fractionation procedures involving ionic properties, (c) considerable solubility in organic solvents, and (d) peculiarities of the peptide map that were related to the foregoing features. Peptide maps were obtained after proteolytic digestion of the protein moieties of the lowest density lipoprotein fraction, the residual soluble protein, and lymph chylomicrons by means of two-dimensional electrophoresis and chromatography. Unusual maps were obtained in which most of the peptide fragments failed to move upon electrophoresis over a broad pH range, but were readily resolved by chromatography in organic solvents. Strong, although imperfect, resemblance was noted among the peptide maps of all three protein fractions. Preliminary studies of low and high density lipoproteins of rat serum revealed different, more complex peptide maps. No definitive conclusion could be drawn about the specificity of the protein which becomes associated with lipid during absorption through the intestinal mucosa. A speculative interpretation of the aforementioned similarity in peptide maps led us to suggest that lipids in transit become associated with some of the more abundant soluble proteins of the mucosal cells and that the resulting lipoprotein complexes appear in the chylomicrons of intestinal lymph. Thin layer methods of chromatography and electrophoresis were extensively employed. Their convenience and great sensitivity permitted detailed studies to be carried out on submilligram quantities of material.

The clinical spectrum of the sick sinus syndrome (SSS) is described in a series of 56 patients who demonstrated either persistent unexplained sinus bradycardia (group I: eight patients); sinus arrest (group II: 15 patients); or bradycardia with episodic supraventricular tachyarrhythmias (group III: 33 patients). Coronary disease was the most common form of heart disease where etiology could be determined, but in 25 patients no clear etiologic diagnoses could be established. Thirty-three patients showed associated electrocardiographic conduction disturbances. Symptoms were common and were produced by both bradycardia and tachycardia. Eight patients in the bradycardia-tachycardia group experienced cerebral embolization. Despite bother-some symptoms, only six of the 56 patients died over an average follow-up of 7 years, and only one of these deaths appeared related to an arrhythmia. Drug therapy of bradycardia was generally ineffective, but digitalis was frequently helpful in patients with tachycardia. Electrical pacing was uniformly successful in treating symptoms of bradycardia but was disappointing in preventing tachyarrhythmias.

The echocardiogram of the anterior leaflet of the mitral valve (ECHO) was compared to hemodynamic and cineroentgenographic data to evaluate its accuracy in timing mitral valve (MV) opening and closure, and to validate it as an indicator of MV motion. The ECHO, high speed cineroentgenography at 250 frames/sec, and/or measurement of intracardiac pressures allowed accurate timing of the events of MV motion in dogs on right heart bypass. The intersection of left ventricular and left atrial pressures in early diastole preceded the onset of rapid anterior motion of ECHO (D' point) by 17 to 33 plus or minus 7.6 msec; r equals 0.98. The onset of left ventricular systole occurred before the termination of final rapid posterior motion of the ECHO in end diastole (Co point) by 25 plus or minus 10 msec; r equals 0.96. Radiopaque clips were attached to the free edges of both leaflets of the MV. Cineroentgenographically determined plots of clip distance from the ultrasound transducer were morphologically similar to the simultaneously recorded ECHO. A delay of 23 plus or minus 3 (0 to 40) msec was observed in the ECHO peaks of diastolic anterior excursion compared to clip motion. Contrast medium advances beyond the free edges of MV leaflets mixing with left ventricular blood 43 plus or minus 3 msec after initial separation. These cineroentgenographic studies elucidate nonuniformity of leaflet motion responsible for ECHO delays. Thus, ECHO D' and Co correlate well with hemodynamic indicators of MV opening and closure. However, ECHO motion, although qualitatively similar, is unpredictably delayed compared to cineroentgenography of clips on the MV free edge. Since the ECHO correlates well with hemodynamic indices of MV opening and closure, this noninvasive technique can be used as a reference in the timing of intracardiac events and in the determination of systolic and diastolic time intervals.

A case with a mixed pattern of pacemaker failure is presented, “Runaway” pacemaker with ventricular capture at 250 beats per minute occurred three days after the development of syncope associated with intermittent loss of pacing artifact. Presumed protection by placement of a temporary pacemaker upon admission was unfounded. This case argues for rapid diagnosis of pacemaker failure, followed by prompt surgical exploration and repair of the pacing system.