Search

Background: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is a recently recognized condition where biomarkers and prognosis are less well studied than in MI with obstructive coronary artery disease (MI-CAD). We therefore aimed to investigate the one-year prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) levels in MINOCA in comparison to MI-CAD., Methods: In this registry-based cohort study, we used data from patients with a discharge diagnosis of MI, admitted between 2009 and 2013 to Swedish hospitals using the hs-cTnT assay. Only patients without previously known coronary artery disease were considered. Patients with and without coronary stenosis >50% were regarded to have MI-CAD and MINOCA, respectively. Assessed outcomes included all-cause mortality, cardiovascular (CV) mortality and major CV events (MACE), defined as the composite of CV death or admissions for non-fatal MI, heart failure (HF) or ischemic stroke., Results: The study cohort consisted of 1639 MINOCA and 17,304 MI-CAD patients. In adjusted analyses, hs-cTnT (ln) in MINOCA patients predicted all-cause mortality (HR 1.32 [95% CI 1.11-1.56]), CV mortality (HR 2.11 [95% CI 1.51-2.96]) and MACE (HR 1.44 [95% CI 1.20-1.72]). Hs-cTnT (ln) also predicted readmissions for HF (HR 1.51 [95% CI 1.51-2.96]) but not non-fatal MI or stroke. Interaction analyses suggested that hs-cTnT (ln) was at least as prognostic in patients with MINOCA compared to MI-CAD., Conclusions: Hs-cTnT levels in MINOCA patients are strong and independent predictors of adverse outcome. Consideration of hs-cTnT levels is important for risk assessment of MINOCA patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

B-type (brain) natriuretic peptide (BNP) forms a peptide family with A-type (atrial) natriuretic peptide (ANP), which is involved in the regulation of blood pressure and fluid volume. We have demonstrated that BNP is a novel cardiac hormone secreted predominantly from the ventricle and that plasma levels of BNP markedly increase in proportion to the severity of congestive heart failure. Spasm of a major coronary artery (coronary spasm) is the cause of variant angina and can be induced by hyperventilation. We examined whether BNP infusion suppresses coronary spasm in patients with variant angina. The effect of BNP infusion on anginal attacks induced by hyperventilation was studied in 11 patients with variant angina in whom the attacks were reproducibly induced by hyperventilation. This study was performed in the early morning on 3 consecutive days. Fourteen minutes after infusion of BNP was begun (day 2, 0.05 micrograms/kg/min) or saline (days 1 and 3), hyperventilation was started and continued for 6 minutes. Anginal attacks were induced in all 11 patients by hyperventilation on days 1 and 3, respectively. Anginal attacks were not induced in any patient on day 2 (BNP infusion). Fourteen minutes after BNP infusion was begun, plasma BNP levels increased from 23.7 +/- 6.7 pg/ml to peak levels of 2591 +/- 255 pg/ml (p < 0.01) and plasma ANP levels increased from 28.9 +/- 7.5 pg/ml to peak levels of 69.2 +/- 13.2 pg/ml. Five minutes after BNP infusion was finished, plasma levels of cyclic guanosine monophosphate (cGMP) increased from 20.3 +/- 7.4 pg/ml to peak levels of 63.5 +/- 13.7 pg/ml (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of coronary vasospasm in the pathogenesis of myocardial infarction is unclarified. Among 212 patients with myocardial infarction in whom percutaneous transluminal coronary angioplasty (PTCA) or coronary thrombolysis was not performed at the acute stage, 21 patients (10%) showed no significant coronary stenosis (the degree of stenosis was less than 50% of the luminal diameter) by coronary angiography 4 weeks after myocardial infarction. Among them, 11 (52%) had preinfarction angina at rest, including two with variant angina, and nine (43%) had postinfarction angina at rest. Intracoronary ergonovine maleate induced coronary vasospasm in 12 (75%) of 16 patients examined. Coronary vasospasm occurred in the infarct-related coronary arteries in all patients, and importantly, multivessel coronary vasospasm occurred in 11 patients (69%). The infarct size was relatively small in these patients: (1) seven patients (33%) had Q wave myocardial infarction while 14 patients (67%) had non-Q wave myocardial infarction; (2) peak creatine phosphokinase (CPK) was lower than 1000 IU/ml in all patients; and (3) thallium-201 (Tl-201) scintigraphic study showed no perfusion defect in 8 of 18 patients. There was only one patient with congestive heart failure and no patient died. These results suggest that coronary vasospasm may play an important role in the pathogenesis of myocardial infarction in patients without significant coronary stenosis. The relatively small infarct size suggests that coronary reperfusion occurred in the early stages of myocardial infarction.

Experiences in 81 patients with variant angina were reviewed with the goal of determining which clinical features were associated with the greatest risk of angina-linked cardiac arrest (13 patients) or sudden unexpected death (9 patients). The risk of occurrence of one of these actually or potentially fatal events was approximately tripled by the presence of either a history of angina-linked syncope or documentation of serious arrhythmia complicating attacks. An unexpected finding was that the risk was increased 1.5-fold by the absence of high-grade organic coronary stenosis. Cardiac arrest and sudden death are important risks of variant angina, which can occur without the presence of severe organic coronary stenosis. These risks can be reduced by adequate vasodilator therapy that includes a calcium channel blocker.

The serum lipid and lipoprotein levels in 15 patients with vasospastic angina were compared with those in 33 patients with no angiographic coronary stenosis and no vasospastic angina after intracoronary acetylcholine infusion. The serum level of apolipoprotein A-I in patients with vasospastic angina (112 +/- 6 mg/dl) was significantly lower (p < 0.05) than that in patients without vasospasm (128 +/- 4 mg/dl). However, there were no differences between the two groups in the serum levels of cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein A-II, and apolipoprotein B. Thus apolipoprotein A-I may play some role in the prevention of vasospastic angina.

Electrocardiographic signs of diffuse three-vessel coronary artery spasm may show various findings including no ST segment changes, according to whether or not a difference of an electrical gradient develops between the anterior and inferior regions because of global ischemia. This study suggests that diffuse three-vessel coronary artery spasm must be considered when the 12-lead electrocardiogram (ECG) shows no important ST segment changes with episodes of angina and diffuse coronary artery spasm during an ergonovine provocation test in patients with strongly suspected variant angina.

We examined the pathogenesis of angina pectoris in 101 patients with one-vessel disease except those with 99% to 100% occlusion. The attacks could not be induced or could not be reproducibly induced by maximal treadmill exercise at the same hour of different days within a week period in 54 (53.5%) of the patients. In the 47 patients whose attacks were reproducibly induced by the exercise, propranolol, 80 mg orally, did not suppress the attacks in 41 (87.2%) of the patients. Diltiazem, 90 mg, and nifedipine, 20 mg given orally, suppressed the attacks completely in 39 (83.0%) of the 47 patients and in 36 (81.8%) of the 44 patients, respectively. Coronary arteriography showed that dynamic obstruction of the artery supplying the area of myocardium represented by ST segment deviation appeared during the attacks and disappeared with subsidence of the attacks in all 55 patients in whom coronary arteriography was done during the attack. We conclude that angina pectoris is usually caused not by increased myocardial oxygen demand but by dynamic coronary obstruction or by a combination of both in most patients with one-vessel disease.

The association of coronary thrombosis and transmural myocardial infarction is well documented. We have recently observed apparent intracoronary thrombi in patients with unstable myocardial ischemia without transmural infarction. To assess the frequency and angiographic characteristics of intracoronary defects consistent with thrombi, we reviewed the angiograms of all patients undergoing catheterization within 1 month of the onset of unstable angina or the intermediate coronary syndrome. Of 129 such patients, eight (6.2%) had nonoccluding, hazy, or nonopacified intracoronary filling defects consistent with thrombus in angiographically well-opacified vessels. All defects were just distal to a significant (80% to 99%) coronary stenosis. In each instance the thrombus-involved vessel supplied a myocardial segment referable to the electrocardiographically defined area of ischemia. Support for the theory that the intracoronary defects were thrombi includes three patients with enlargement of the filling defects, who underwent repeat angiography within 7 days, and two patients with embolization of defect fragments. Furthermore these defects were angiographically similar to poststenotic intraluminal defects seen transiently in some patients after partial intracoronary streptokinase recanalization. In conclusion, we have observed, angiographically, intracoronary filling defects consistent with thrombus in some patients with unstable myocardial ischemia.

To examine the alteration in control function of the heart, which may account for the pathophysiologic condition precipitating coronary arterial spasm, the dynamic property of heart rate response to exercise in vasospastic angina was evaluated by using our previously developed frequency analytic procedure. We studied 21 patients with vasospastic angina, divided into two groups (active angina and inactive angina) and 12 normal control subjects. When compared with the transfer function of the heart rate control system in normal control subjects, the transfer function in patients with active vasospastic angina showed moderately lower gain, especially in the middle frequency range, and significantly delayed phase angle over the whole frequency range, especially in the middle and high frequency ranges. These abnormalities were not observed in inactive vasospastic angina. The present exercise test to detect abnormal heart rate control can feasibly be used in the detection and management of vasospastic angina.

Coronary angiography was performed at rest and during bicycle exercise immediately after the onset of angina and significant ST segment elevation or depression in the ECG. Of 11 patients, six showed significant reduction of coronary lumen diameter at the site of organic stenosis; mean values of stenosis (range) before and during exercise were 55% (25% to 88%) and 98% (89% to 100%), respectively. Five patients did not have any diameter change of the organic lesion; mean values of stenosis (range) before and during exercise were 84% (74% to 89%) and 84% (73% to 92%), respectively. Excluding the areas of these stenoses, diameters of left main coronary artery, proximal, middle, and distal left anterior descending, circumflex, and right coronary artery segments were measured before and during exercise. Diameter in each coronary artery segment during exercise was not significantly changed from that before exercise, both in the groups with and without diameter reduction. Exercise provoked a localized worsening of coronary artery stenosis without changing the diameter in the remaining artery. These findings suggest that the worsening of stenosis might be caused by a regional abnormality of the coronary artery that is not necessarily related to the degree of organic stenosis.

Recent clinical and laboratory observations indicate that coronary artery spasm may play a role in the pathophysiology of ischemic heart disease. The majority of patients with ischemic heart disease have coronary atherosclerosis. The prevalence of coronary artery spasm in these patients is unknown. However, current evidence suggests that patients with rest angina have a higher incidence of coronary artery spasm than do patients with reproducible effort angina. Coronary artery spasm may initiate or contribute to acute myocardial infarction, but recent evidence obtained in patients undergoing thrombolytic therapy during the early phases of myocardial infarction suggests that it is not a common occurrence. Although numerous examples of ventricular tachycardia and ventricular fibrillation occur during episodes of coronary artery spasm, the incidence of coronary artery spasm in association with sudden death is unknown. Provocative testing with ergonovine maleate reveals that the highest incidence of provocable coronary artery spasm is found in patients with rest angina. In patients with the syndrome of variant angina, coronary artery spasm is nearly always provocable.

Spasm, either of heart muscle or of coronary arteries, has long been postulated as a possible cause of anginal pain. Yet early necropsy observations of obstructed coronary arteries in cases of cardiac death so focused attention on the fixed obstruction as the source of myocardial ischemia that the role of vasospasm is only now becoming evident. Further, the fact that spasm most commonly occurs together with a fixed obstruction has obscured its presence and its role in producing myocardial ischemia. In classic angina, ischemia results when increased oxygen demand is placed on the heart; the variant form of angina results from a restriction in myocardial oxygen supply, frequently even at rest. The mechanisms of coronary vasospasm are unclear, although such factors as excessive alpha-adrenergic activity, imbalances in prostaglandin synthesis, and increased Ca++ entry into myocytes through alterations in pH and blood gas tensions have been implicated.

Twelve patients were entered prospectively into a randomized double-blind study comparing the efficacy of nifedipine and isosorbide dinitrate (ISDN) in the treatment of variant angina pectoris due to coronary artery spasm. Using the diary technique, both anginal episodes and nitroglycerin tablets consumed were recorded during the pretrial, no drug period, and both active drug phases. During the baseline pretrial period, an average of 1.1 anginal episodes/day occurred with reduction to 0.28/day during nifedipine treatment and 0.39/day during ISDN treatment. Headache was the major side effect during ISDN treatment, occurring in 9 of 11 (81%) patients; and nonheart failure related pedal edema during nifedipine treatment, occurring in 4 of 12 (33%) patients. Intolerable side effects necessitating cessation of treatment occurred in two patients during nifedipine treatment and in three patients during ISDN treatment. Patients preferred nifedipine over ISDN because of increased efficacy and fewer uncomfortable side effects. We conclude that both nifedipine and ISDN are effective therapy for coronary spasm, but that nifedipine was more effective and was preferred by the majority of patients.

This study was performed to determine the sensitivity of thallium imaging vs ECG monitoring for detecting coronary artery spasm noninvasively following intravenous ergonovine administration as compared to simultaneous coronary angiography. Thirty-two patients with insignificant coronary artery disease and chest pain underwent 12-lead ECG monitoring, thallium imaging, and coronary arteriography following the administration of 0.05, 0.1, 0.2, and 0.3 mg of ergonovine given 5 minutes apart or until chest pain occurred. One minute following the last dose of ergonovine, 2.5 mCi of thallium-201 was injected intravenously, and a final ECG was recorded and repeat coronary arteriography performed. Within 10 minutes following the injection of thallium, imaging was performed in the 40-degree and 70-degree left anterior oblique and anterior projections. The ECG, thallium study, and coronary arteriogram were read blindly and results were compared. The ECG, angiogram, and thallium study were read as positive if the following occurred, respectively: greater than or equal to 1 mm ST segment elevation, depression, or T wave reversal; greater than 50% vessel narrowing,; and reversible perfusion defect. Five patients were excluded from analysis because of either catheter-induced spasm, suboptimal thallium studies, or protocol violations. Of the 27 patients included for analysis, six had chest pain, five had a positive angiogram, five had a positive thallium study, and one had a positive ECG. The sensitivity of thallium vs ECG monitoring was 80% vs 25%, and the accuracy was 92% vs 80%. We conclude that thallium imaging greatly increases the noninvasive detection of ergonovine-induced coronary spasm as compared with the ECG with no loss of accuracy.

To assess the contribution of coronary vasospasm to chest pain in patients with nontransmural myocardial infarction, we performed a controlled trial of prophylactic antivasospastic therapy. Fifty patients with nontransmural infarction received either nifedipine or placebo in a double-blind randomized trial. Chest pain occurred in 52% of treated patients (38 episodes on 35 days) compared to 48% of control patients (42 episodes on 33 days). Concurrent therapy was comparable in the two groups. Recurrent infarction occurred in 12% and was comparable between groups. Ejection fraction was similar and was unchanged throughout the study in both groups. Logistic regression failed to identify predictors for recurrent chest discomfort. These data indicate that potent antivasospastic therapy does not reduce the incidence of recurrent chest pain or infarction. Thus, remediable coronary vasospasm is not likely to be a major cause of post infarction ischemia in patients with nontransmural infarction.

Coronary angiography of both right and left coronary arteries, using the Sones technique, was performed during the attack of total spastic obstruction in 11 patients with clinically documented history of variant angina. None of the patients had more than 70% stenosis of organic atherosclerosis in any coronary artery and none had a history of myocardial infarction. Total spastic obstruction occurred spontaneously in 3 of 11 patients, and was provoked by ergonovine maleate in eight patients. Six patients had total spastic obstruction in the left anterior descending coronary artery, four patients had total obstruction in the right coronary artery, and one patient had total obstruction in the left anterior descending and right coronary arteries. In 7 of 11 patients, the coronary artery distal to the total spastic obstruction received collaterals from the nonspastic artery. The collaterals disappeared promptly when the spastic coronary artery was patent. These patients had ST segment elevation in the ECG during the attacks. In the remaining four patients, the spastic artery did not receive any collaterals from the nonspastic artery, associated with ST segment elevation during the attacks. These findings suggest that the brief, repetitive total occlusion of the coronary artery may stimulate the enlargement of collaterals. These collaterals may not always function to prevent the ischemia of the myocardium on the ECG.

Twelve cases of myocardial infarction (MI) were documented in 11 of 39 patients who had coronary artery spasm (CAS) that was observed by angiography either before MI (3 patients), after MI (5 patients), or both before and after MI (3 patients). MI corresponded in location to sites of ECG changes of myocardial ischemia during spontaneous angina pectoris in 7 of 7 patients and to the region of myocardium supplied by the vessel in which CAS was observed by angiography in each patient. MI occurred in the distribution of the right coronary artery in 8 patients and of the left coronary artery in 4 patients. Of 12 vessels that supplied infarcted regions of myocardium, 7 vessels had greater than or equal to 50% diameter fixed coronary artery narrowing (CAN), but the remaining 5 vessels had minimal (10%) or no fixed CAN. In those patients who were studied after MI, coronary angiography demonstrated that only 3 of 9 vessels in the distribution of infarcted regions of myocardium were completely occluded. Clinical follow-up for an average of 1.3 years after MI showed that 7 patients continued to have chest pain, 2 patients were asymptomatic, and 2 patients died suddenly 9 weeks and 1 year, respectively, after MI. Therefore, among our patients with CAS demonstrated by angiography, MIs (1) were frequent (28%), (2) occurred in the distribution of observed coronary spasm, (3) were frequently (5 of 12 arteries) in the distribution of vessels having minimal or no fixed narrowing, and (4) were often (6 of 9 arteries) in the distribution of vessels that were demonstrated to be patient after MI.