Arie Roth

Acute Myocardial Infarction Associated With Pregnancy

Acute myocardial infarction (AMI) during pregnancy or the early post-partum period is rare but has been shown to be associated with poor maternal as well as fetal outcome. Major changes in both diagnosis and treatment of AMI in the nonpregnant patient have lead to improved outcome which may also affect pregnant patients. The purpose of this paper is to review available information related to the pathophysiology and clinical profile and provide recommendations for the diagnosis and management of AMI occuring during pregnancy and the early post-partum period.

Acute Myocardial Infarction Associated with Pregnancy

Acute myocardial infarction rarely occurs in women of childbearing age and has been estimated to occur in only 1 in 10 000 women during pregnancy [1, 2]. Since the first report in 1922 [3], many additional cases have been published in the literature [4-109], indicating the unique features of acute myocardial infarction that can significantly affect maternal and fetal outcomes. With the current trend of childbearing at an older age and the ongoing effects of cigarette smoking, stress, and cocaine use, the occurrence of acute myocardial infarction during pregnancy can be expected to increase. We review the clinical aspects of acute myocardial infarction in the gestational and early postpartum period in 125 well-documented cases and attempt to establish recommendations for the management of this condition. Methods A literature search for acute myocardial infarction during pregnancy was done using MEDLINE and Index Medicus. All original articles were obtained from the University of Southern California library, interlibrary communications, or the authors of the articles. Translators were used to translate all original articles written in foreign languages. Only cases of acute myocardial infarction that were documented by chest pain, standard electrocardiographic criteria, and enzymatic changes (or histologic changes in patients who died) were selected for review. Six cases that were described as acute myocardial infarction but did not fulfill the aforementioned criteria were excluded from the analysis. Epidemiologic data were used to compare selected patients who had acute myocardial infarction in the antepartum (as many as 24 hours before labor), peripartum (within 24 hours before or after delivery), and postpartum (from 24 hours to 3 months after delivery) periods. We make recommendations on the basis of available information, with the understanding that the 125 cases identified in our review may not represent all patients who have acute myocardial infarction associated with pregnancy and that reporting may be biased in favor of unusual cause, presentation course, and outcome. Epidemiology Although acute myocardial infarction has occurred in pregnant women at all stages of pregnancy and at ages between 16 and 45 years, this event usually occurs in the third trimester in women older than 33 years (Table 1). Patients who had acute myocardial infarction in the postpartum period (mean age SD, 29 6 years) were substantially younger than women who had acute myocardial infarction in the antepartum (mean age, 33 6 years) or peripartum (mean age, 34 5 years) period. In addition, acute myocardial infarction associated with pregnancy has been noted to occur most commonly in multigravidas and is most commonly located in the anterior wall. Most maternal deaths occurred either at the time of infarction (usually resulting in an undelivered child) or within 2 weeks of infarction [1] (usually in association with labor and delivery). No association could be found, however, between maternal death and method of delivery (Table 2). The cumulative reported maternal mortality rate was 21%; rates in the peripartum or postpartum period were higher than those in the antepartum period. Most fetal deaths (10 of 16 [62%]) were associated with maternal deaths, and maternal survival was usually accompanied by normal fetal outcome. The remaining fetal deaths resulted from spontaneous abortion or unexplained stillbirth. Overall, fetal mortality (13%) was lower than maternal mortality. Table 1. Select Data in 123 Pregnancies Complicated by 125 Myocardial Infarctions Table 2. Select Data in Survivors and Nonsurvivors of Myocardial Infarction during Pregnancy and the Puerperium When coronary artery morphology was studied (through use of angiography or at autopsy) during pregnancy or shortly thereafter (54% of reported patients), coronary atherosclerosis with or without intracoronary thrombus was found in 43% of patients (29 of 68) and definite or probable coronary thrombus without evidence of atherosclerotic disease was present in 21% of patients (14 of 68). Atherosclerotic disease was found more commonly in women with acute myocardial infarction in the antepartum period (58%) than in those with acute myocardial infarction in the peripartum (12%) or postpartum (29%) period. Coronary dissection was found in 16% of patients (11 of 68) and was the primary cause of infarction in the postpartum period (33%). Normal coronary arteries were reported in 29% (20 of 68) of all cases and 75% of those with acute myocardial infarction in the peripartum period. Causes Risk factors for myocardial infarction in young women generally include a family history of coronary artery disease; familial hyperlipoproteinemia; low levels of high-density lipoprotein cholesterol, high levels of low-density lipoprotein cholesterol, or both; diabetes mellitus; cigarette smoking; and previous use of oral contraceptives [110]. Although it seems to be the primary cause of acute myocardial infarction during pregnancy, atherosclerotic disease was found in less than half of patients in whom coronary anatomy was investigated (Table 1). Other potential causes include thrombosis, coronary artery spasm (either spontaneous [37] or induced by bromocriptine mesylate [7, 17]), coronary artery dissection [15, 31, 71], collagen vascular disease [16, 41], Kawasaki disease [18], cocaine use [24], aortic valvular stenosis, aortic prosthetic valve thrombosis [23], sickle cell chronic lung disease [65], pheochromocytoma [93], and fibrosis of a coronary ostium secondary to repeated trauma by a papillary fibroelastoma with a long stalk that was strategically located in front of the ostium [100]. Despite the many potential causes, their rarity during childbearing age may explain the low rate of acute myocardial infarction during pregnancy. Twenty-nine percent of patients in whom coronary artery anatomy was defined were found to have normal coronary arteries (Table 1). Because a thrombus was found without atherosclerotic disease in 21% of the patients, a transient coronary spasm resulting in acute coronary thrombosis as a result of the hypercoagulable state of pregnancy is a possible explanation. Failure to identify similar cases of thrombosis in other patients may be related to doing angiography in late stages of pregnancy. Because acute myocardial infarction has been related to pregnancy-induced hypertension and preeclampsia, enhanced vascular reactivity to angiotensin II [111] and norepinephrine [112] and endothelial dysfunction [113] [which have been reported in these conditions] may also promote coronary constriction. Other suggested causes of coronary spasm are 1) decreased uterine perfusion in the supine position leading to renin release and angiotensin production [32] and 2) ergot derivatives that are used to control postpartum [33] or postabortion [21] hemorrhage or to suppress lactation [7, 13, 14]. The profound alterations in the coagulation and fibrinolytic system that occur during pregnancy increase the risk for thrombosis. These alterations include decreased releasable tissue plasminogen activator (t-PA) [114-116], increased fast-acting t-PA inhibitor [116, 117], change in the level of coagulation factors [115, 118], and reduction in functional protein S levels [26, 119, 120]. Cigarette smoking during pregnancy further increases risk for thrombosis because of enhanced platelet aggregability [121]. Hypercoagulation is further augmented at the time of separation of the placenta, which is a major source of t-PA inhibitor [119]. Coronary arterial dissections related to pregnancy have been reported to occur in the antepartum and postpartum periods, but most cases seem to occur in the immediate postpartum period (Table 1) [122, 123]. It has been suggested [15] that angiographically normal coronary arteries seen in many patients who had acute myocardial infarction in the peripartum period may represent healed or spontaneously repaired coronary dissections. The cause for dissection may be hormonally mediated biochemical and histologic changes that have been reported to occur in arterial walls during gestation, such as loss of normal corrugation in elastic fibers, fragmentation of reticular fibers, and decrease in the content of acid mucopolysaccharide [124, 125]. The marked increases in blood volume, stroke volume, and heart rate that are usually seen during pregnancy [126] can increase myocardial oxygen demand. At the same time, the physiologic anemia and decreased diastolic blood pressure that occur during gestation may reduce myocardial oxygen supply and contribute to the development of myocardial ischemia when coronary blood supply is compromised. Anxiety, pain, and uterine contraction may further augment these ischemic events during labor and delivery and may be associated with as much as a threefold increase in oxygen consumption. In the puerperium, increased hemodynamic load may be further increased by enhanced return of venous blood to the heart with relief of caval compression and shift of blood from the contracting emptied uterus into the systemic circulation. The hemodynamic changes that normally occur during late pregnancy and during labor, delivery, and the puerperium [126] may contribute to poor outcome in women who have an acute myocardial infarction in the peripartum period. Diagnosis and Clinical Considerations Early diagnosis of acute myocardial infarction during pregnancy is often hindered by mistaking its signs and symptoms for normal manifestations of pregnancy [127] and because of a low level of suspicion. Diagnosis in pregnant women is confirmed as it is in nonpregnant patients, primarily by electrocardiographic and changes in enzyme levels. Therefore, it is important to note that electrocardiographic changes that mimic myocardial ischemia have been reported in as many as 37% of parturients having elective cesarean section [128, 129]. Echocardiography can be done safely durin

Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure.

Sustained therapy with nitroglycerin (NTG) has been reported to provoke the development of early tolerance. Because continuous intravenous NTG infusion is commonly used in patients with coronary artery disease and heart failure, we evaluated the incidence of early tolerance developed within the first 24 hr of therapy in 31 responders to NTG. After documentation of response to NTG, defined as a 10 mm Hg or greater or a 30% or greater reduction in mean pulmonary arterial wedge pressure (PAWP), 16 patients were blindly, randomly assigned to receive placebo and 15 patients were continued on same-dose NTG. Both groups showed an identical fall in PAWP at peak NTG titration (11 +/- 4 mm Hg). Discontinuation of NTG in the placebo group resulted in a rapid increase in PAWP to levels not significantly different from baseline (19 +/- 5 mm Hg at 2 hr vs 23 +/- 6 mm Hg at baseline; p = NS). In the NTG group, PAWP fell from 27 +/- 9 to 14 +/- 7 mm Hg, was 16 +/- 9 mm Hg at 2 hr (p less than .05 vs baseline), and continued to be significantly lower than baseline for 8 hr; however, due to attenuation of effect, PAWP values at 12, 20, and 24 hr were not significantly different from placebo or baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating adiponectin concentrations in patients with congestive heart failure

Objectives: To determine concentrations of adiponectin and its predictive value on outcome in a cohort of patients with congestive heart failure (CHF). Methods: Serum and clinical data were obtained for outpatients with clinically controlled CHF (n  =  175). Serum concentrations of adiponectin, C reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin (IL) -1β, IL-6, IL-8, IL-10, IL-12, tumour necrosis factor α and CD-40 ligand were determined. The association of adiponectin with the clinical severity of CHF was sought as well as the predictive value of this adipokine on mortality, CHF hospitalisations or the occurrence of each of these end points. Results: Concentrations of adiponectin were significantly increased in patients with CHF. Patients with higher New York Heart Association class had significantly higher serum concentrations of adiponectin. Adiponectin serum concentrations were lower in patients with diabetes and CHF as well as in patients with ischaemic cardiomyopathy. Serum adiponectin concentration was positively associated with age and NT-proBNP but was negatively correlated with C reactive protein concentrations. Serum adiponectin above the 75th centile was found to be an independent predictor of total mortality, CHF hospitalisations or a composite of these end points over a two-year prospective follow up. Conclusion: Adiponectin is increased in CHF patients and predicts mortality and morbidity.

Analysis of Coronary Ultrasound Thrombolysis Endpoints in Acute Myocardial Infarction (ACUTE Trial) Results of the Feasibility Phase

BACKGROUND It has been demonstrated that therapeutic ultrasound effects ultrasound thrombolysis by selectively disrupting the fibrin matrix of the thrombus. This study was conducted to evaluate the clinical feasibility of percutaneous transluminal coronary ultrasound thrombolysis in acute myocardial infarction (AMI). METHODS AND RESULTS Consecutive patients (n = 15) with evidence of anterior AMI and Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow in the left anterior descending artery underwent coronary ultrasound thrombolysis. Angiographic follow-up was performed after 10 minutes and 12 to 24 hours. Ultrasound induced successful reperfusion (TIMI grade 3 flow) in 87% of the patients. Adjunct percutaneous transluminal coronary angioplasty (PTCA) after ultrasound thrombolysis produced a final residual stenosis of 20 +/- 12% as determined by quantitative coronary angiographic analysis. There were no adverse angiographic signs or clinical effects during the procedure. There was no change in the degree of flow in any of the patients at the 12- to 24-hour angiograms. During hospitalization, 1 patient had recurrent ischemia on the fifth day after the procedure, and emergent catheterization revealed occlusion at the treatment site. The patient was successfully treated with PTCA. CONCLUSIONS These results suggest that ultrasound thrombolysis has the potential to be a safe and effective catheter-based therapeutic modality in reperfusion therapy for patients with AMI and other clinical conditions associated with intracoronary thrombosis.

Rapid resolution of ST elevation and prediction of clinical outcome in patients undergoing thrombolysis with alteplase (recombinant tissue-type plasminogen activator): results of the Israeli Study of Early Intervention in Myocardial Infarction.

Alteplase (recombinant tissue-type plasminogen activator (rt-PA)) was infused within four hours of onset of symptoms in 286 patients with acute myocardial infarction. Delayed coronary angiography was performed 72 hours after admission with coronary angioplasty if indicated. Electrocardiographic monitoring was continuous during the first hour of treatment. The sum of the ST segment elevations (sigma ST) was calculated on electrocardiograms recorded at entry and an hour later. ST elevations resolved rapidly within one hour of treatment in 189 patients and persisted in 97 patients. Rapid resolution of ST elevation correlated with angiographic coronary patency as determined by coronary angiography 72 hours after admission. The patients with rapid resolution of sigma ST had significantly smaller infarcts and a better clinical outcome than the patients with persistent ST elevation. sigma ST values at entry and one hour after treatment had no additional independent predictive value. Rapid resolution of ST elevations in patients undergoing thrombolysis with alteplase was associated with a significantly smaller release of creatine kinase, better preservation of left ventricular function, lower morbidity, and less short and long term mortality. Rapid resolution of sigma ST elevation is an efficient indicator of clinical outcome in groups of patients with acute myocardial infarction undergoing thrombolysis with alteplase.

Randomized controlled trial of late in-hospital angiography and angioplasty versus conservative management after treatment with recombinant tissue-type plasminogen activator in acute myocardial infarction

Although both the European Cooperative Study Group and the Thrombolysis in Myocardial Infarction IIB trial indicated that angiography and angioplasty as routine measures after thrombolytic treatment do not improve clinical outcome in patients with acute myocardial infarction, the potential benefit of angioplasty may have been negated by the fact that the procedure was performed too soon (less than 32 hours) after admission. A similar study was designed in which delayed invasive treatment was compared with conservative treatment in 201 patients with acute myocardial infarction given recombinant tissue-type plasminogen activator. The 97 patients randomized to the invasive group underwent routine coronary angiography and angioplasty 5 +/- 2 days after thrombolytic therapy, whereas the 104 patients randomized to the conservative group underwent angiography only for recurrent postinfarction angina or exercise-induced ischemia. Baseline characteristics of both groups were similar. In the invasive group, 92 patients underwent angiography, 49 angioplasty and 11 coronary artery bypass surgery. In the conservative group, 40 patients experienced early ischemia, 39 underwent angiography, 20 angioplasty and 4 coronary artery bypass surgery. Reinfarction rate and preservation of left ventricular function at discharge or 8 weeks after discharge did not differ in the 2 groups. Total mortality after a mean follow-up of 10 months was 8 of 97 in the invasive and 4 of 104 in the conservative groups (p = 0.15). However, if only patients who died after the timing of the scheduled protocol catheterization in the invasive arm were included, mortality was 5 of 94 and 0 of 100 in the invasive and conservative treatment groups, respectively (p = 0.02). (ABSTRACT TRUNCATED AT 250 WORDS)

Shoulo thrombolytic therapy be administered in the mobile intensive care unit in patients with evolving myocardial infarction? A pilot study

The growing recognition of the importance of early thrombolysis in evolving myocardial infarction was the basis for the present study, which evaluated the effectiveness, feasibility and safety of prehospital thrombolytic therapy. In a relatively small study, 118 patients were allocated to receive either prehospital treatment with recombinant tissue-type plasminogen activator (rt-PA) in the mobile intensive care unit (group A, 74 patients) or hospital treatment (group B, 44 patients). A total of 120 mg of rt-PA was infused over a period of 6 h. All patients were fully heparinized and underwent radionuclide left ventriculography and coronary angiography during hospitalization. Although group A was treated significantly earlier than group B after onset of symptoms (94 +/- 36 versus 137 +/- 45 min, respectively; p less than 0.001), no significant differences were observed between the groups in 1) extent of myocardial necrosis, 2) global left ventricular ejection fraction at discharge, 3) patency of infarct-related artery, 4) length of hospital stay, and 5) mortality at 60 days. However, a trend to a lower incidence of congestive heart failure at hospital discharge was observed in the prehospital-treated compared with the hospital-treated group (7% versus 16%, respectively; p = NS). No major complications occurred during transportation. It is concluded that myocardial infarction can be accurately diagnosed and thrombolytic therapy initiated relatively safely during the prehospital phase by the mobile intensive care team, thus instituting a beneficial clinical trend in favor of prehospital thrombolysis.

Pregnancy-Associated Acute Myocardial Infarction: A Review of Contemporary Experience in 150 Cases Between 2006 and 2011

The incidence of coronary artery disease (CAD) in women of child-bearing age is low, and acute myocardial infarction (AMI) is uncommon.1,2 Pregnancy, however, has been shown to increase the risk of AMI ≈3-fold compared with the risk in nonpregnant women of similar age.2–5 Although previous studies have provided some data related to the incidence of pregnancy-associated MI (PAMI), clinical characteristics, risk factors, and outcome1,2,4 more information is needed on the mechanisms of AMI, the efficacy and safety of standard therapy, and the applicability of guideline recommendations designed for the general AMI population, to women with PAMI. The aim of this study was therefore to review contemporary data on PAMI in an attempt to provide recommendations for the management of this condition. A literature search for cases with AMI related to pregnancy was performed using PubMed and Google Scholar. References from these studies were cross-checked to obtain additional studies that may have been missed by the original search. All original articles were obtained online or by interlibrary communication. Articles published in languages other than English were translated by medical translators. A total of 134 cases published in the literature from 2006 to 2011 not included in a previous review4 were included in this study.6–124 In addition, 7 cases presented at the First International Congress on Cardiac Problems in Pregnancy in 2010 (Valencia, Spain) and 9 patients treated or consulted by the authors were also included in the analysis. Recommendations were made on the basis of available clinical information, with the understanding that the cases published in the literature and reviewed by us do not represent all the patients who developed PAMI during the period of the study and that reporting may therefore be incomplete and biased. …

Pause-dependent torsade de pointes following acute myocardial infarction: a variant of the acquired long QT syndrome.

OBJECTIVES We report on a previously unrecognized form of the long QT syndrome (QT interval prolongation and pause-dependent polymorphic ventricular tachycardia [VT]) entirely related to myocardial infarction (MI). BACKGROUND Polymorphic VT in the setting of acute MI generally occurs during the hyperacute phase, is related to ischemia, and is not associated with QT prolongation. Although QT prolongation after MI is well described, typical pause-dependent polymorphic VT (torsade de pointes) secondary to uncomplicated MI was previously unknown. METHODS Of 434 consecutive admissions for acute MI, 8 patients had progressive QT prolongation that led to typical torsade de pointes. None of these patients had active ischemia or other known causes of QT prolongation. These patients were compared with 100 consecutive patients with uncomplicated MI who served as controls. RESULTS The incidence of torsade de pointes following MI was 1.8% (95% confidence interval 0.8% to 3.6%). The QTc intervals of patients and controls were similar on admission. The QTc lengthened by day 2 in both groups, but more so in patients with torsade de pointes (from 470 +/- 46 to 492 +/- 57 ms [p < 0.05] and from 445 +/- 58 to 558 +/- 84 ms, respectively [p < 0.01]). Maximal QT prolongation and torsade de pointes occurred 3 to 11 days after infarction. Therapy included defibrillation, magnesium, lidocaine and beta-blockers. Three patients required rapid cardiac pacing. The long-term course was uneventful. CONCLUSIONS Infarct-related torsade de pointes is uncommon but potentially lethal. An acquired long QT syndrome should be considered in patients recovering from MI who experience polymorphic VT as specific therapeutic measures are mandatory.