Richard Gorlin

Angiographic progression of coronary artery disease and the development of myocardial infarction.

There are few data on angiographic coronary artery anatomy in patients whose coronary artery disease progresses to myocardial infarction. In this retrospective analysis, progression of coronary artery disease between two cardiac catheterization procedures is described in 38 patients: 23 patients (Group I) who had a myocardial infarction between the two studies and 15 patients (Group II) who presented with one or more new total occlusions at the second study without sustaining an intervening infarction. In Group I the median percent stenosis on the initial angiogram of the artery related to the infarct at restudy was significantly less than the median percent stenosis of lesions that subsequently were the site of a new total occlusion in Group II (48 versus 73.5%, p less than 0.05). In the infarct-related artery in Group I, only 5 (22%) of 23 lesions were initially greater than 70%, whereas in Group II, 11 (61%) of 18 lesions that progressed to total occlusion were initially greater than 70% (p less than 0.01). In Group I, patients who developed a Q wave infarction had less severe narrowing at initial angiography in the subsequent infarct-related artery (34%) than did patients who developed a non-Q wave infarction (80%) (p less than 0.05). Univariate and multivariate analysis of angiographic and clinical characteristics present at initial angiography in Group I revealed proximal lesion location as the only significant predictor of evolution of lesions greater than or equal to 50% to infarction. This retrospective study suggests that myocardial infarction frequently develops from previously nonsevere lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic evolution of coronary artery morphology in unstable angina

As previously reported in acute presentations of unstable angina, an identifiable characteristic coronary artery lesion has been found in about 70% of cases at coronary arteriography. This takes the form of an eccentrically placed convex stenosis with a narrow neck due to one or more overhanging edges or irregular, scalloped borders, or both. To study the evolution of lesions responsible for unstable angina, coronary artery anatomy and morphology on angiography were evaluated in patients with stable angina progressing to unstable angina. Group I comprised 25 patients with a history of stable angina who were restudied after an acute episode of unstable angina and Group II comprised 21 patients with little or no change in symptoms between catheterizations. Progression of coronary disease occurred in 19 (76%) of 25 patients in Group I compared with 7 (33%) of 21 in Group II (p less than 0.001). Of the 25 lesions with progression in Group I, 17 progressed to less than 100% and 8 to 100% occlusion. Eighteen of these 25 lesions in Group I were previously insignificant (less than 50% occlusion on the first catheterization). In contrast, of the eight lesions with disease progression in Group II, only two were previously insignificant while six showed at least 50% occlusion on the initial study. The eccentric lesion was seen in 71% of all lesions with progression to less than 100% occlusion in Group I, but it was not seen in any Group II vessel with progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary angiographic morphology in myocardial infarction: A link between the pathogenesis of unstable angina and myocardial infarction

It has previously been shown that analysis of coronary morphology can separate unstable from stable angina. An eccentric stenosis with a narrow neck or irregular borders, or both, is very common in patients who present with acute unstable angina, whereas it is rare in patients with stable angina. To extend these observations to myocardial infarction, the coronary morphology of 41 patients with acute or recent infarction and nontotally occluded infarct vessels was studied. For all patients, 27 (66%) of 41 infarct vessels contained this eccentric narrowing, whereas only 2 (11%) of 18 noninfarct vessels with narrowing of 50 to less than 100% had this lesion (p less than 0.001). In addition, a separate group of patients with acute myocardial infarction who underwent intracoronary streptokinase infusion were also analyzed in similar fashion. Fourteen (61%) of 23 infarct vessels contained this lesion after streptokinase infusion compared with 1 (9%) of 11 noninfarct vessels with narrowing of 50 to less than 100% (p less than 0.01). Therefore, an eccentric coronary stenosis with a narrow neck or irregular borders, or both, is the most common morphologic feature on angiography in both acute and recent infarction as well as unstable angina. This lesion probably represents either a disrupted atherosclerotic plaque or a partially occlusive or lysed thrombus, or both. The predominance of this morphology in both unstable angina and acute infarction suggests a possible link between these two conditions. Unstable angina and myocardial infarction may form a continuous spectrum with the clinical outcome dependent on the subsequent change in coronary supply relative to myocardial demand.

Hemodynamic and clinical tachyphylaxis to prazosin-mediated afterload reduction in severe chronic congestive heart failure.

Sequential doses of 5 mg of oral prazosin hydrochloride were administered to eight patients with severe chronic congestive heart failure refractory to conventional therapy. Initial doses of the drug produced marked increases in cardiac index (+0.87 I/min/m2) associated with substantial decreases in left ventricular filling pressure (-10.7 mm Hg), total systemic vascular resistance (2118 to 1154 dyn-sec-cm-5), and heart rate (89 to 76 beats/min). However, serial administration of the same dose at 12-24-hour intervals was accompanied by the rapid development of tachyphylaxis, such that the magnitude of hemodynamic effects with second doses was less than 50% of the magnitude of effects seen with first doses (p < 0.01), and third doses produced no overall significant hemodynamic responses. Diuresis with furosemide failed to restore the circulatory effects of prazosin, and the use of 10-mg doses improved cardiovascular performance to only a small extent. Only two of eight patients had sustained hemodynamic responses large enough to justify chronic oral ambulatory therapy. Administration of oral hydralazine caused hemodynamic improvement superior to even high-dose prazosin therapy (p < 0.02).

AIR TRAVEL AND THROMBOTIC EPISODES: THE ECONOMY CLASS SYNDROME

Le risque de thrombose des veines profondes et dembolie pulmonaire est eleve lors des voyages aeriens de longue duree, surtout en classe economique. Discussion de 6 observations, dont 3 avec facteurs predisposants dans les antecedents

Coronary flow studies in patients with left ventricular hypertrophy of the hypertensive type: Evidence for an impaired coronary vascular reserve

Increased myocardial blood flow occurs in ventricular hypertrophy, but flow per 100 grams of myocardium remains normal. The increase in flow may be obtained at the expense of the existing coronary vascular reserve or by an increase in the vascular bed. The coronary vascular reserve was studied by analyzing the hyperemic reaction to selective injection of contrast agent into the coronary arteries in 25 patients: a control group (9 patients) with chest pain syndrome, normal coronary arteries and a normal left ventricle (Group I) and 16 patients with aortic stenosis, left ventricular hypertrophy and normal coronary arteries (Group II). The hyperemic response in Groups I and II was 73.3 +/- 2.2 and 65.8 +/- 9.1 percent, respectively (difference not significant). Group II was subdivided into two groups: Group IIA had five patients with a left ventricular mass of less than 200 g (mean 158.8 +/- 25.9); this group had a hyperemic response of 102.3 +/- 9.9 percent. Group IIB had 11 patients with a left ventricular mass of more than 200 g (mean 308.9 +/- 22.5) and a hyperemic response of 49.27 +/- 10.42 percent. The hyperemic response was correlated with the diastolic left ventricular-aortic gradient (r = +0.64, p less than 0.001), left ventricular mass (r = -0.51, p less than 0.01) and aortic diastolic pressure (r = +0.636, p less than 0.001). Group I had a left ventricular mass similar to that of Group IIA (124.9 +/- 9 and 158.8 +/- 26 g, respectively) but a lower hyperemic response (73.3 +/- 2 and 102.3 +/- 10 percent, respectively). These data suggest that severe left ventricular hypertrophy is associated with a reduction in coronary vascular reserve; it is speculated that this decrease in the vascular reserve capacity may be related to the ischemic component of hypertrophic heart disease.

Right ventricular performance in patients with coronary artery disease.

While left ventricular (LV) performance in patients with coronary artery disease (CAD) has been extensively investigated, little attention has been given to right ventricular (RV) function in this disease. For this purpose, a new geometric model for RV volume has been developed and RV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI) and ejection fraction (EF) have been determined from biplane RV cineangiograms in 26 patients. Eight patients served as normal (control) subjects (group I). Eighteen patients with obstructive CAD comprised two other groups: six who had no significant disease of the right coronary artery (RCA) (group II) and 12 who had a high grade RCA lesion (group III). The mean values for EDVI, SVI and EF in group I were 76 ± 11 ml/m2, 50 ± 6 ml/m2, and 66 ± 6%. The only significant difference between groups I and II was that SVI was lower in group II than in group I (P < 0.01). No measurements in groups II and III were statistically different from each other. However, markedly subnormal values were found in group III (EDVI: 61 ± 16 ml/m2, SVI: 33 ± 10 ml/m2 and EF: 52 ± 7%); all values being significantly lower (SVI and EF: P < 0.001; EDVI: P < 0.05) than in group I. RV end-diastolic pressure was normal in all patients. These findings may be related to 1) reduced RV compliance, 2) distorted LV geometry, 3) possible RV ischemia or 4) reduced Frank-Starling effect.

Anatomic-physiologic links between acute coronary syndromes.

THE BEST THERAPY for a given morbid condition is possible only when both its pathoanatomy and pathophysiology are clearly understood. This certainly applies to the acute ischemic syndromes of the heart. Early in the study of myocardial infarction the term was considered to be synonymous with acute coronary thrombosis. 2 This theory remained intact for many years, to be challenged only within the past two decades when it was seen that autopsies did not always uncover an acute coronary thrombosis subtending an area of established infarction. While the elegant pathologic studies of Mitchell and Schwartz3 did demonstrate a close relationship, they also found coronary thrombosis less often as death occurred further in time from the acute event. They hypothesized that recanalization might well have occurred in the interim. Roberts4 later proposed that coronary thrombosis might occur secondary to the acute myocardial infarction rather than as a cause. However, during the last few years, technical advances have brought to light a definitive role of thrombosis in the pathogenesis of the acute coronary syndromes. The role of plaque rupture and thrombosis in the acute coronary syndromes. Recent pathologic studies of the coronary arterial system have revealed that rupture, cracking, or ulceration of atherosclerotic plaques is a common finding at autopsy in patients with coronary atherosclerotic disease.58 Disrupted atherosclerotic plaques are often associated with mural or occlusive thrombi, usually anchored in cracks in the ruptured plaque. The part of the thrombus directly overlying the fissure is composed predominantly of platelets. Evidence derived from serial coronary arteriography,9 and that obtained after reperfusion by thrombolysis,0 at operation during acute coronary artery syndromes, and from postmortem coronary arteriography,2 have

Angiographic demonstration of a common link between unstable angina pectoris and non-Q-wave acute myocardial infarction.

The coronary morphology of ischemia-related arteries in unstable angina and Q-wave acute myocardial infarction (AMI) has been described. An eccentric stenosis with overhanging edges or irregular borders (type II eccentric) was seen in most lesions less than 100% occluded and probably represented plaque disruption, nonocclusive thrombus or both. The coronary morphology of non-Q AMI has not been described. Thus, the angiograms of 106 consecutive patients catheterized with either unstable angina (n = 73) or non-Q AMI (n = 33) and an identifiable ischemia-related artery were prospectively analyzed. Non-Q AMI was diagnosed by prolonged chest pain and new and persistent ST-T changes or creatine phosphokinase twice the normal level. The results showed a higher incidence of total occlusion of the ischemia-related artery in non-Q AMI (21%) compared with unstable angina (8%) (p = 0.1). The coronary morphology of nonoccluded ischemia-related arteries was similar with preponderance of type II eccentric lesions in both unstable angina and non-Q AMI. These lesions were found in 65% of ischemia-related arteries in non-Q AMI but were uncommon (3%) in nonischemia-related arteries with significant (50% to 100%) stenoses. Therefore, the type II eccentric lesion is a sensitive and specific marker of less than 100% occluded ischemia-related arteries in both unstable angina and non-Q AMI. These similarities in coronary morphology suggest a similar pathogenesis, which, as previously suggested, may relate to plaque disruption with or without thrombus. Unstable angina and non-Q AMI appear to represent part of a continuous spectrum of acute coronary artery disease. Further, the management of patients with non-Q AMI should be similar to patients with unstable angina and possibly include anticoagulation and consideration for early catheterization.

Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man.

The administration of verapamil to patients receiving, β-adrenergic blocking drugs is reported to produce adverse circulatory reactions, but a systematic investigation of this potential drug interaction has not been performed in man. We administered 40-, 80- and 120-mg doses of verapamil orally to 15 patients with angina pectoris who were receiving high doses of propranolol or metoprolol. Verapamil produced dose-dependent decreases in cardiac performance: with 120 mg, cardiac index decreased by 0.38 I/min/m2, stroke volume index decreased by 2.8 ml/beat/m2 and heart rate decreased by 6 beats/min, associated with increases in pulmonary capillary wedge (2.2 mm Hg) and mean right atrial pressures (1.7 mm Hg) (all p < 0.01); two patients had marked, but asymptomatic, hypotensive reactions. In contrast, repeat administration of 120-mg doses of verapamil 24–30 hours after withdrawal of A blockade produced no significant cardiodepressant effects despite significantly higher plasma levels of verapamil than during propranolol therapy (383.1 vs 205.1 ng/ml, p < 0.01). In conclusion, verapamil produces significant negative inotropic and chronotropic effects in patients treated with 3-adrenergic antagonists; combination therapy should therefore be used with caution in patients with angina pectoris.