Recurrent apical ballooning despite treatment with verapamil.

OBJECTIVE: To report a case of recurrent tako-tsubo syndrome that developed despite treatment with calcium channel antagonists. CASE SUMMARY: A 76-year-old woman with past medical history of ischemic heart disease and mild chronic asthma presented in 2001 with clinical characteristics and laboratory markers consistent with myocardial ischemia. Coronary angiogram was done with successful balloon angioplasty to LAD stenosis. Ventriculogram and echocardiography demonstrated apical ballooning believed to represent aneurysm formation. Several months later, a follow-up echocardiogram (ECG) revealed normal LV size and function with no wall motion abnormalities. ECG was unremarkable. In 2004, the patient was admitted with dyspnea, chest pain and ST elevation in ECG with normal troponin. Coronary angiogram demonstrated patent coronary tree. Left ventriculogram revealed apical ballooning sparing the base of the heart. Medically controlling the asthma attack led to clinical, echocardiographic and remarkable electrocardiographic normalization within days. Rest thallium perfusion scan done within 48 h demonstrated isolated fully reversible defect in the apex after 24 h suggesting a microvessel etiology. CONCLUSION: Tako-tsubo cardiomyopathy is an increasingly recognized condition. We report here the first case of tako-tsubo recurrence despite treatment with verapamil, and suggest a microvessel pathophysiology supported by rest thallium scan.

Serum of cytomegalovirus-infected mice induces monocyte chemoattractant protein-1 expression by endothelial cells.

Inflammation plays a central role in atherogenesis. It was hypothesized that infection of apolipoprotein E-deficient mice with murine cytomegalovirus (MCMV) increases serum levels of proinflammatory cytokines, which may induce "proatherosclerotic" changes in endothelial cells (ECs). Serum samples were collected from uninfected and infected mice. ELISA was used to determine cytokine serum levels and monocyte chemoattractant protein-1 (MCP-1) levels in the supernatant of mouse ECs incubated with serum-containing medium. Serum samples from infected mice induced MCP-1 expression by ECs. These serum samples contain interferon (IFN)-gamma, whereas IFN-gamma was undetectable in serum samples from uninfected mice. Preincubating infected mouse serum with anti-IFN-gamma monoclonal antibody significantly decreased serum-induced EC expression of MCP-1. Thus, MCMV infection increases IFN-gamma serum levels, such serum can induce MCP-1 in ECs, and the serum-induced MCP-1 expression is due, at least in part, to IFN-gamma. If these changes in EC function also occur in vivo in response to infection, they could exacerbate atherogenesis.

Effect on survival of acute myocardial infarction in Killip classes II or III patients undergoing invasive coronary procedures.

The purpose of the present study was to determine whether patients with acute myocardial infarction (AMI) in Killip class II or III are likely to benefit from catheterization and coronary revascularization performed within 30 days of AMI. The study population was drawn from 2 national surveys performed during 1996 and 1998 in 26 coronary care units operating in Israel. Our analysis included 3,113 patients with AMI who were divided into 2 groups according to their admission Killip class: 2,484 patients (80%) in Killip class I, of whom 1,408 (57%) underwent cardiac catheterization and 1,076 were treated noninvasively; and 629 patients in Killip class II or III, of whom 314 (50%) underwent cardiac catheterization and 315 were managed conservatively. Patients in Killip class II or III who were treated invasively had lower mortality rates than their counterparts who were treated noninvasively at 30 days: 7.6% versus 15.6%, respectively (adjusted odds ratio [OR] 0.52, 95% confidence interval [CI] 0.28 to 0.92), and thereafter from 30 days to 6 months, 4.3% versus 13.6%, respectively (OR 0.34, 95% CI 0.16 to 0.68). In Killip class I patients, an invasive versus noninvasive management was not associated with a better outcome at 30 days: 1.6% versus 3.2%, respectively (OR 0.58, 95% CI 0.32 to 1.05), but with similar mortality rates at 30 days to 6 months, 1.9% versus 2.0%, respectively (OR 1.46, 95% CI 0.79 to 2.74). Thus, the present study suggests that patients with AMI in Killip class II or III on admission may benefit from cardiac catheterization and revascularization performed within 30 days from admission, whereas patients with AMI in Killip class I are less likely to benefit from this approach.

Discordant cellular and humoral immune responses to cytomegalovirus infection in healthy blood donors: existence of a Th1-type dominant response.

Previous studies have documented discordant cellular and humoral immune responses to subjects exposed to HIV-1, and that the nature of such responses may determine susceptibility and resistance to disease. We determined whether there is a spectrum of cellular versus humoral immunodominant responses to cytomegalovirus (CMV) infection. Blood samples from 50 healthy blood donors were tested for anti-CMV IgG antibodies and for proliferative responses of peripheral blood mononuclear cells (PBMC) to CMV antigens. Four patterns of immune responses to CMV were found: no detectable response (30%, Ab(-)/Tc(-)), anti-CMV IgG only (28%, Ab(+)/Tc(-)), both anti-CMV IgG and T lymphocyte proliferation to CMV antigens (18%, Ab(+)/Tc(+)), and, interestingly, T lymphocyte proliferation to CMV only (24%, Ab(-)/Tc(+)). To determine whether these immunodominant phenotypes correlate with the ability of PBMC to secrete IL-2 and IFN-gamma in response to CMV antigens, we found that a greater percentage of individuals with a T cell proliferative response to CMV antigens (Ab(-)/Tc(+) and Ab(+)/Tc(+)) responded with increased IL-2 (P = 0.001) and IFN-gamma levels (P = 0.002), compared to those without a proliferative response (Ab(-)/Tc(-) and Ab(+)/Tc(-)). Our data therefore demonstrate that different individuals exhibit different immunodominant patterns of response to CMV. In particular, some individuals who are exposed to CMV fail to develop an antibody response but do develop cellular immunity. Whether these different patterns predict susceptibility or resistance to CMV-induced disease remains to be determined.

Improved survival of patients with acute myocardial infarction with significant left ventricular dysfunction undergoing invasive coronary procedures.

BACKGROUND: Acute myocardial infarction (AMI) associated with significant left ventricular dysfunction (LVD) indicates a poor prognosis. Previous studies suggested that revascularization improves survival of patients with AMI complicated by cardiogenic shock. However, other studies that suggested that revascularization improves survival of stable patients with significant LVD did not specifically address patients who had recently had an AMI. OBJECTIVES: Our purpose was to determine whether patients with thrombolysis-treated AMI associated with significant LVD are likely to incur a survival advantage from catheterization and coronary revascularization performed within 30 days after AMI. METHODS: The study population was drawn from the Argatroban in Acute Myocardial Infarction-2 (ARGAMI-2) trial, which included 1200 patients with AMI, all of whom received thrombolytic therapy. Our analysis included 737 patients for whom LV function was estimated by echocardiography. Two hundred two patients had significant LVD; of them, 117 (58%) underwent cardiac catheterization and 85 were treated noninvasively. Among 535 patients without significant LVD, 291 (54%) underwent cardiac catheterization and 244 were treated noninvasively. RESULTS: Compared with a noninvasive approach, an invasive approach resulted in reduced 30-day and 6-month mortality rates in patients with significant LVD: 4.3% versus 10.6%, adjusted odds ratio (OR) 0.26, 95% confidence interval (CI) 0.04 to 1.18, and 6.1% versus 15.5%, OR 0.27, 95% CI 0.06 to 0.98, respectively. A similar comparison in patients without significant LVD resulted in comparable 30-day and 6-month mortality rates for both patient groups: invasively versus noninvasively treated, 0.7% versus 0.8%, OR 1.04, 95% CI 0.04 to 12.7, and 1.4% versus 1.7%, adjusted OR 1.60, 95% CI 0.20 to 9.87. CONCLUSIONS: The current study suggests that AMI patients with significant LVD may benefit from cardiac catheterization and revascularization performed early after AMI, whereas in patients without significant LVD the outcome of those treated invasively or conservatively was similar.

Antibodies to human heat-shock protein 60 are associated with the presence and severity of coronary artery disease: evidence for an autoimmune component of atherogenesis.

BACKGROUND: Antibodies to mycobacterial heat-shock protein (HSP) 65 have been reported to be associated with carotid artery thickening. We examined whether antibodies to human HSP60 are associated with the risk of coronary artery disease (CAD). METHODS AND RESULTS: Blood samples from 391 patients (62% men, mean age 57 years) being evaluated for CAD by coronary angiography were tested for IgG antibodies to human HSP60 by ELISA. We found that 75% of the study subjects had anti-HSP60 antibodies. The prevalence of CAD was increased in seropositive compared with seronegative patients (68% versus 49%, P:=0.0009). Mean titers of HSP60 antibodies were higher in CAD patients than in non-CAD patients (P:=0.008). No association between HSP60 antibodies and infection or inflammation was found. Importantly, HSP60 antibodies were related to disease severity. The prevalence of HSP60 antibodies was 76%, 80%, and 85% in patients with 1-, 2-, and 3-vessel disease, compared with 64% in patients without CAD (P: for trend=0.003). A similar association between increasing antibody titers and number of diseased vessels was also found (P:=0.03). Significant associations between antibodies to HSP60 and CAD severity persisted after adjustment for traditional risk factors by age, race, sex, smoking, diabetes, hypercholesterolemia, hypertension, and C-reactive protein levels. Adjusted OR for number of vessels diseased was 1.86 (95% CI 1.13 to 3.04). CONCLUSIONS: This is the first study demonstrating a significant association between human HSP60 antibodies and both the presence and severity of CAD.

Coronary vasomotor tone: determinants and effect on coronary angioplasty.

BACKGROUND: Coronary artery reference diameters increase during coronary angioplasty (PTCA). However, in clinical practice, balloon selection is often based on a preceding diagnostic coronary angiogram. It is common to find that the initially selected balloon is undersized due to resting vasomotor tone. This may contribute to a suboptimal angioplasty result. METHODS: Quantitative coronary angiography (QCA) was used to determine the magnitude of coronary artery vasodilatation over baseline angiography and its impact on balloon size choice. Pre-PTCA clinical and treatment variables were analyzed for their potential contribution to resting vasomotor tone. RESULTS: QCA of reference coronary diameters was performed in a group of 103 patients undergoing PTCA. Post PTCA proximal and distal reference diameters significantly increased over baseline. The average increase of the proximal segment was 0.368 mm (13.6%) p < 0. 001 and of the distal segment 0.567 mm (24.8%) p < 0.001. The initial nominal balloon diameter was smaller than the post PTCA proximal segment by an average of 0.34 mm (12.6%) p < 0.001. Of the clinical and treatment variables examined age < 65 years and pre-PTCA beta blocker use, significantly affected baseline vasomotor tone p < 0.05. CONCLUSIONS: Routine diagnostic angiography underestimates the true diameter of the coronary artery. Due to baseline vasomotor tone, coronary reference segments can be expected to increase approximately 13% in diameter during successful PTCA. Patients under 65 years of age and those using beta-blockers may have a significantly increased baseline vasomotor tone. Underestimation of coronary artery diameter based on initial angiography necessitated a second, larger balloon in 16.5% of cases.

Usefulness of the Killip classification for early risk stratification of patients with acute myocardial infarction in the 1990s compared with those treated in the 1980s. Israeli Thrombolytic Survey Group and the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.

The classification introduced in 1967 by Killip et al has proved to be a useful method for early risk stratification of patients with acute myocardial infarction (AMI). Over the past 3 decades the overall mortality due to AMI has decreased significantly. The present study evaluates the usefulness of the Killip classification as a method for early risk stratification of patients with AMI in the 1990s. One thousand eight hundred seventy-three consecutive AMI patients were hospitalized in 25 coronary care units operating in Israel, and were followed for 1 year. Higher Killip class was found to be associated with increased in-hospital and 1-year mortality, in thrombolysis- and nonthrombolysis-treated patients (30-day mortality for all patients was 5%, 21%, 35%, and 67% in Killip classes I to IV, respectively). The overall mortality among AMI patients in the 1990s was found to be lower for each Killip class compared with a comparable patient population with AMI, hospitalized in Israel in the 1980s. Thus, the Killip classification is a useful method for early risk stratification of AMI patients in the 1990s.