Joe K. Bissett

Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: Report of the program on the surgical control of the hyperlipidemias (posch)

BACKGROUND AND METHODS The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, was designed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease. The study population consisted of 838 patients (417 in the control group and 421 in the surgery group), both men (90.7 percent) and women, with an average age of 51 years, who had survived a first myocardial infarction. The mean follow-up period was 9.7 years. RESULTS When compared with the control group at five years, the surgery group had a total plasma cholesterol level 23.3 percent lower (4.71 +/- 0.91 vs. 6.14 +/- 0.89 mmol per liter [mean +/- SD]; P less than 0.0001), a low-density lipoprotein cholesterol level 37.7 percent lower (2.68 +/- 0.78 vs. 4.30 +/- 0.89 mmol per liter; P less than 0.0001), and a high-density lipoprotein cholesterol level 4.3 percent higher (1.08 +/- 0.26 vs. 1.04 +/- 0.25 mmol per liter; P = 0.02). Overall mortality and mortality due to coronary heart disease were reduced, but not significantly so (deaths overall [control vs. surgery], 62 vs. 49, P = 0.164; deaths due to coronary disease, 44 vs. 32, P = 0.113). The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower (control vs. surgery, 39 vs. 24; P = 0.021). The value for two end points combined--death due to coronary heart disease and confirmed nonfatal myocardial infarction--was 35 percent lower in the surgery group (125 vs. 82 events; P less than 0.001). During follow-up, 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting (P less than 0.0001). A comparison of base-line coronary arteriograms with those obtained at 3, 5, 7, and 10 years consistently showed less disease progression in the surgery group (P less than 0.001). The most common side effect of partial ileal bypass was diarrhea; others included occasional kidney stones, gallstones, and intestinal obstruction. CONCLUSIONS Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infarction and reduces their subsequent morbidity due to coronary heart disease. The role of this procedure in the management of hypercholesterolemia remains to be determined. These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression.

A Randomized Controlled Trial of a Paclitaxel-Eluting Stent Versus a Similar Bare-Metal Stent in Saphenous Vein Graft Lesions: The SOS (Stenting Of Saphenous Vein Grafts) Trial

OBJECTIVES The aim of this study was to compare the frequency of angiographic restenosis and clinical events between a paclitaxel-eluting stent (PES) and a similar bare-metal stent (BMS) in saphenous vein graft (SVG) lesions. BACKGROUND There are conflicting and mostly retrospective data on outcomes after drug-eluting stent implantation in SVGs. METHODS Patients requiring SVG lesion stenting were randomized to BMS or PES. The primary study end point was binary in-segment restenosis at 12-month follow-up quantitative coronary angiography. Secondary end points included death, myocardial infarction, ischemia-driven target vessel and lesion revascularization, and target vessel failure. RESULTS Eighty patients with 112 lesions in 88 SVGs were randomized to a BMS (39 patients, 43 grafts, 55 lesions) or PES (41 patients, 45 grafts, 57 lesions). Binary angiographic restenosis occurred in 51% of the BMS-treated lesions versus 9% of the PES-treated lesions (relative risk: 0.18; 95% confidence interval [CI]: 0.07 to 0.48, p < 0.0001). During a median follow-up of 1.5 years the PES patients had less target lesion revascularization (28% vs. 5%, hazard ratio: 0.38; 95% CI: 0.15 to 0.74, p = 0.003) and target vessel failure (46% vs. 22%, hazard ratio: 0.65; 95% CI: 0.42 to 0.96, p = 0.03), a trend toward less target vessel revascularization (31% vs. 15%, hazard ratio: 0.66; 95% CI: 0.39 to 1.05, p = 0.08) and myocardial infarction (31% vs. 15%, hazard ratio: 0.67; 95% CI: 0.40 to 1.08, p = 0.10), and similar mortality (5% vs. 12%, hazard ratio: 1.56; 95% CI: 0.72 to 4.11, p = 0.27). CONCLUSIONS In SVG lesions, PES are associated with lower rates of angiographic restenosis and target vessel failure than BMS.

Continued Benefit From Paclitaxel-Eluting Compared With Bare-Metal Stent Implantation in Saphenous Vein Graft Lesions During Long-Term Follow-Up of the SOS (Stenting of Saphenous Vein Grafts) Trial

OBJECTIVES This study sought to report the long-term outcomes after drug-eluting stent (DES) implantation in saphenous vein graft (SVG) lesions in the SOS (Stenting of Saphenous Vein Grafts) trial. BACKGROUND The long-term outcomes after DES implantation in SVGs are poorly studied. Apart from the SOS trial, the only other randomized trial comparing DES with bare-metal stents (BMS) in SVGs reported higher mortality in the DES group at 32 months. METHODS In the SOS trial, 80 patients with 112 lesions in 88 SVGs were randomized to a BMS or paclitaxel-eluting stent (PES) and demonstrated improved short-term angiographic and clinical outcomes with PES. Extended clinical follow-up was subsequently obtained. RESULTS Mean age was 67 ± 9 years, and all patients were men. The indications for stenting included acute coronary syndrome in 60% and stable angina in 31% of patients. The mean SVG age was 12 ± 6 years. The baseline characteristics of the patients in the 2 study groups were similar. Procedural success was achieved in 77 patients (96%). During a median follow-up of 35 months, compared with patients randomized to BMS, those receiving PES had a lower incidence of myocardial infarction (hazard ratio [HR]: 0.32, p = 0.01), target lesion revascularization (HR: 0.20, p = 0.004), target vessel revascularization (HR: 0.41, p = 0.03), and target vessel failure (HR: 0.34, p = 0.001) as well as a trend toward less definite or probable stent thrombosis (HR: 0.15, p = 0.08). All-cause mortality (HR: 2.04, p = 0.19) and cardiac mortality (HR: 0.62, p = 0.51) did not differ between groups. CONCLUSIONS During long-term follow-up, use of PES was associated with significantly better clinical outcomes than BMS in SVG lesions. (Stenting of Saphenous Vein Grafts Trial [SOS]; NCT00247208).

Prohormone atrial natriuretic peptides 1–30, 31–67, and 99–126 increase in proportion to right ventricular pacing rate

To determine whether heart rate contributes to release of three new peptide hormones synthesized in the heart, right ventricular pacing at rates of 100, 125, 150, and 180 bpm was performed in six dogs with measurement of the plasma concentration of these peptides at each pacing rate while right atrial and systemic blood pressures were simultaneously monitored. These three peptides of the 126-amino-acid prohormone of atrial natriuretic factor (ANF), consisting of amino acids 1-30 (pro ANF 1-30), 31-67 (pro ANF 31-67), and 99-126 (ANF), increased incrementally at paced heart rates of 125, 150, and 180 bpm (r = 0.8, p less than 0.001). Right atrial pressure decreased with increasing heart rate but systemic blood pressure did not decrease until the heart rate was 180 bpm, at which time these peptides had obtained their maximal circulating concentrations. After pacing, mean right atrial pressure and levels of ANF returned to prepacing values within 30 minutes. Mean arterial blood pressure, on the other hand, increased throughout the 120-minute period after pacing. At 2 hours after pacing, levels of pro ANFs 1-30 and 31-67 were elevated compared with prepacing values. These data demonstrate that, at heart rates of 125 bpm and above, pro ANF 1-30, pro ANF 31-67, and ANF (99-126) are simultaneously and incrementally released in direct proportion to heart rate. The sustained elevation in pro ANFs 1-30 and 31-67 seen 2 hours after pacing suggests that they may contribute to the prolonged diuresis seen after cardiac pacing or tachycardia.

Ectopic Ventricular Prematurity and Its Relationship to Ventricular Tachycardia in Acute Myocardial Infarction in Man

In order to determine the role of the coupling interval of a premature ventricular contraction (PVC) in the development of paroxysmal ventricular tachycardia (PVT) during the early phase of acute myocardial infarction in man, 52 male patients with documented acute myocardial infarction had 24-hour Holter monitoring commenced within 24 hours of the onset of prolonged chest pain. Review of the tape recordings revealed that 27 patients had PVT documented, while 25 patients did not. Analysis of the data on the two groups showed that the frequency of PVCs, coupled PVCs, and accelerated idioventricular rhythm (AIVR) were found to be associated with a significantly increased incidence of ventricular tachycardia.The mean coupling interval of the PVCs initiating episodes of ventricular tachycardia was not significantly different from either the mean coupling interval of the isolated PVCs in the patients with PVT or the mean coupling interval of the PVCs in the patients without PVT. This suggests that the coupling interval of a ventricular ectopic is a poor predictor of ventricular tachycardia in the early phases of acute myocardial infarction.

Digoxin-quinidine interaction: Changes in canine tissue concentration from steady state with quinidine☆

Tissue concentrations of tritiated digoxin inthe dog are altered by simultaneous administration of quinidine. Serum levels rise as tissue concentration decreases significantly in all tissue except brain tissue, where an increase of 51 percent is noted over that of the control digitalized state. The digitalis toxicity associated with digoxin-quinidine interaction appears to be associated with rising brain levels of digoxin and falling levels in the myocardium. These findings suggest a neurally mediated form of toxicity with this interaction related to a change in the space of distribution. The question of possible loss of inotropic effect associated with diminished myocardial digoxin concentration requires further study.

The relationship of paroxysmal ventricular tachycardia complicating the acute phase and ventricular arrhythmia during the late hospital phase of myocardial infarction to long-term survival

The long-term prognosis of paroxysmal ventricular tachycardia (PVT) complicating acute myocardial infarction remains unevaluated. Significant ventricular arrhythmia in the patient after infarction is said to carry a poor prognosis with regard to survival. To evaluate these two important aspects of myocardial infarction in man, 56 patients with documented myocardial infarction had Holter monitoring performed during the initial 24 hours and prior to hospital discharge. In 38 of the 45 survivors, Holter monitoring was repeated an average of 19 months after infarction. There were eight cardiac deaths during follow-up. Data analysis revealed that of 18 patients with PVT during the acute phase, one died during follow-up and 17 survived long-term. Even though the incidence of complex PVCs prior to hospital discharge and at long-term follow-up was higher in patients with PVT during the acute phase than in those without PVT, survival appeared unaffected. Thus, PVT during the acute phase of myocardial infarction and complex PVCs at the time of hospital discharge are not incompatible with long-term survival.

Ventricular Arrhythmia in Chronic Stable Angina Pectoris with Surgical or Medical Treatment

Since both propranolol therapy and saphenous-vein bypass surgery have become accepted treatments for patients with symptomatic coronary-artery disease, it is important to determine if either influences the prevalence of ventricular arrhythmias in these patients. Six-hour dynamic electrocardiography was done on 130 patients with chronic stable angina pectoris at least 1 year after being randomized to surgical or medical therapy. All surgical patients had saphenous-vein grafting; 90% of the medical patients received propranolol. Data analysis showed that even though the overall prevalence of premature ventricular contractions was no different in medical and surgical patients, the prevalence of complex premature ventricular contractions was significantly higher in surgically treated patients not receiving propranolol than in propranolol-treated medical patients (p less than 0.05). However, the survival rate was no different in either group, and the quality of life in the surgical patients remained superior.

Atrioventricular conduction patterns in patients with paroxysmal supraventricular tachycardia

Atrioventricular conduction patterns suggestive of dual A-V nodal pathways have been reported in patients with and without a history of paroxysmal A-V nodal re-entrant tachycardia (PSVT). The purpose of this study was to determine whether significant association exists between this conduction pattern and the occurrence of PSVT in man. The pattern of A-V conduction was evaluated at similar pacing rates in 13 patients with documented PSVT and 135 patients with PSVT. Patients without PSVT were divided into groups with normal PR intervals (106 patients), PR intervals of 120 msec. or less (12 patients), and PR intervals of 200 msec. or greater (17 patients). Evidence of dual A-V nodal pathways was found in seven of 13 patients with PSVT and nine of 135 patients without PSVT, including eight of 106 patients with normal PR intervals, none of 12 patients with short PR intervals, and one of 17 patients with PR intervals of 200 msec. or greater. The incidence of dual A-V nodal pathways was significantly greater (P less than 0.01) in patients with PSVT when compared with all other groups. In two of four patients with PSVT, propranolol was found to unmask evidence of dual pathways; no evidence of dual pathways was produced by propranolol in 23 patients without PSVT. The data show that the pattern of dual A-V nodal pathways is common only in patients with PSVT and is significantly less frequent in patients without PSVT regardless of the presence of short or long PR intervals. The results of this study establish a strong association between this conduction pattern and the occurrence of PSVT in man.

Acute and sustained release of atrial natriuretic factor with acute myocardial infarction

The present investigation was designed to determine if acute ischemic cardiac injury causes the release of atrial natriuretic factor (ANF). Seventeen patients with acute myocardial infarction but without clinical evidence of congestive heart failure had their circulating concentration of ANF and creatine phosphokinase monitored daily for 14 days. All 17 patients had an elevated plasma ANF concentration at time of presentation. Maximal increase in ANF was on day 2 and 3 post-infarction. This maximal increase correlated with the size of infarction estimated by the maximal creatine phosphokinase concentration (r = 0.475; p less than 0.05), but did not correlate with the amount of left ventricular dysfunction. ANF began to decrease by day 4 post-infarction and was normal at 10 days post-infarction in 14 of the 17 (82%) patients. At 12 days post-infarction, all 17 patients had normal ANF levels. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured ANF levels in these patients were within our normal range and were significantly lower (p less than 0.001) than those seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina likewise had normal circulating ANF concentrations during prolonged episodes of chest pain. These levels were also significantly lower (p less than 0.001) than the 17 patients with acute infarcts not given tPA. The distinct pattern of release of ANF may be useful as an adjunct to serum cardiac enzymes in determining if a myocardial infarction has occurred.