Helicobacter pylori and Pro-Inflammatory Protein Biomarkers in Myocardial Infarction with and without Obstructive Coronary Artery Disease.

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries.

BACKGROUND: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). OBJECTIVES: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C-protein C inhibitor (APC-PCI) complex. METHODS: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case-control study. Autoantibodies (IgA/G/M) targeting cardiolipin and ß2 glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC-PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. RESULTS: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-ß2 glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC-PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. CONCLUSIONS: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability-measured by increased levels of the APC-PCI complex-were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.

Recurrent Spontaneous Coronary Artery Dissection: Association with Takotsubo Syndrome and Fibromuscular Dysplasia; Comprehensive Review.

Spontaneous coronary artery dissection (SCAD) is a non-traumatic, non-iatrogenic, and non-atherosclerotic separation or dissection of the coronary arterial wall by the formation of an intramural hematoma causing a false lumen leading to compression of the true lumen with a varying degree of coronary blood flow obstruction. One of the important and frequent complications of the disease is the in-hospital and long-term SCAD recurrence. SCAD associated with takotsubo syndrome (TS) has been described in case reports, series of cases and in some studies. Some investigators believe that the association of SCAD and TS is a misdiagnosis. The association of SCAD and fibromuscular dysplasia (FMD) has received major attention during the last 10 years. In this report, the short and long-term SCAD recurrence, SCAD association with TS and FMD are reviewed and demonstrated with illustrative images.

Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries.

BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD). METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age- and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses. RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-κ-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls. CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts.

International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management.

The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians.

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology.

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.

Epidemiology, pathogenesis, and management of takotsubo syndrome.

Takotsubo syndrome is a recently recognized acute cardiac disease entity with a clinical presentation resembling that of an acute coronary syndrome. The typical takotsubo syndrome patient has a unique circumferential left (bi-) ventricular contraction abnormality profile that extends beyond a coronary artery supply territory and appears to follow the anatomical cardiac sympathetic innervation. The syndrome predominantly affects postmenopausal women and is often preceded by emotional or physical stress. Patients with predisposing factors such as malignancy and other chronic comorbidities are more prone to suffer from takotsubo syndrome. The pathogenesis of takotsubo syndrome is elusive. Several pathophysiological mechanisms involving myocardial ischemia (multivessel coronary artery spasm, microvascular dysfunction, aborted myocardial infarction), left ventricular outlet tract obstruction, blood-borne catecholamine myocardial toxicity, epinephrine-induced switch in signal trafficking, and autonomic nervous system dysfunction have been proposed. The syndrome is usually reversible; nevertheless, during the acute stage, a substantial number of patients develop severe complications such as arrhythmias, heart failure including pulmonary edema and cardiogenic shock, thromboembolism, cardiac arrest, and rupture. Treatment of precipitating factors, predisposing diseases, and complications is fundamental during the acute stage of the disease. The epidemiology, pathogenesis, and management of takotsubo syndrome are reviewed in this paper.

Spontaneous coronary artery dissection and takotsubo syndrome: The chicken or the egg causality dilemma.

Acute coronary syndrome (ACS) including spontaneous coronary artery dissection (SCAD) has been reported to trigger its own clinical twin takotsubo syndrome (TS). The pathogenetic association between SCAD and TS remains to be elucidated. The two diseases afflict predominantly women and both conditions may be triggered by an emotional stress factor and an unusual extreme physical exercise. Herein, we describe a case of 54-year-old woman presenting with ACS caused by an obtuso-marginal SCAD. Concurrently, the patient had typical clinical features and course of mid-apical pattern of TS. The causal link between the two conditions is discussed. © 2017 Wiley Periodicals, Inc.

Health-related quality-of-life up to one year after myocardial infarction with non-obstructive coronary arteries.

AIMS: Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) are a heterogenous group and previous studies indicate a decreased Health-related quality-of-life (HRQoL) compared with patients with myocardial infarction with obstructive coronary artery disease and healthy individuals. However, longitudinal data are scarce. Therefore, the aim was to explore HRQoL among patients with MINOCA during a one-year period after the acute event in comparison with a group of healthy individuals and to describe HRQoL in patients with Takotsubo Syndrome (TTS). METHODS AND RESULTS: Patients with MINOCA were recruited from five hospitals in the Stockholm region (SMINC-2 study, clinical trials: NCT2318498). Patients responded to the HRQoL questionnaire RAND-36 between days 2-4, after 6 and 12 months respectively. A sample of population-based individuals was used as a comparison group. A total of 142 MINOCA patients, (70% women) mean age of 56 years, responded. A population-based sample of 317 volunteers (66% women) mean age of 57 years. Patients with MINOCA scored lower than the comparison group in the domains role functioning physical, social functioning, and role functioning emotional (P = 0.01-0.02) at 12 months. In these domains of HRQoL there was no improvement in MINOCA patients during 12 months follow-up. In the domains of energy/fatigue vitality and emotional well-being the scores improved and were similar to the comparison group at 12 months. Patients with TTS scored generally lower on RAND-36 than MINOCA patients without TTS. CONCLUSION: Physical, social, and emotional functioning did not improve during the first year after MINOCA, indicating a need for increased follow-up including psychological support.

Atrio-ventricular block and takotsubo syndrome: A review illustrated with two case reports.

Takotsubo syndrome (TS) can be complicated by life-threatening arrhythmias. Data on the association of AV-block, pacemaker implantation, and TS are scarce. We describe two cases of AV-block associated with TS. AV-block persisted despite the recovery of left ventricular dysfunction during follow-up. A review of AV-block and TS association is provided.

A Novel Descriptive, Intelligible and Ordered (DINO) classification of coronary bifurcation lesions. Review of current classifications.

BACKGROUND: Several classification systems for coronary artery bifurcation lesions (CABL) have been described in the literature, but despite the commendable effort to simplify a difficult subject in interventional cardiology, all of them have certain limitations and shortcomings. METHODS AND RESULTS: The proposed Descriptive, INtelligible and Ordered (DINO) is a new descriptive and clinically oriented system of classifying CABLs. This classification system takes into consideration more details of the side branch angulation relative to the main branch. It uses self-explanatory terms and mnemonic characters (acronyms related to the branches of the bifurcation and the shape of side branch angulation). The DINO classification describes the extent of CABL distribution and designates its localization at the bifurcation region. Moreover, systematized simple and easy to remember terms may form a relevant classification basis for multicenter and meta-analysis investigations. CONCLUSIONS: The DINO is the first verbally anchored, all-inclusive classification system of CABLs. It describes precisely side branch angulation, using self-explanatory and instructive terms that describe both the extent of the lesion's distribution and its localization. The current coronary bifurcation lesion classifications are reviewed.

Bromocriptine-induced coronary spasm caused acute coronary syndrome, which triggered its own clinical twin--Takotsubo syndrome.

Bromocriptine-induced coronary spasm (BICS) causing myocardial infarction has been reported. Association between BICS and Takotsubo syndrome (TS) has not been described. We report on a 37-year-old woman presenting with a clinical picture of acute coronary syndrome 1 day after initiation of treatment with bromocriptine for ablactation 3 weeks after a full-term spontaneous vaginal delivery. Coronary angiography showed diffuse narrowing of a large diagonal branch. Left ventriculography showed widespread hypokinesia extending beyond the diagonal branch supply region. There was a slight elevation of myocardial infarction biomarkers that was disproportional to the degree of left ventricular dysfunction. Follow-up coronary angiography, intravascular ultrasound and left ventriculography showed normal coronary arteries including the diagonal branch and complete normalization of the left ventricular function. Cardiac magnetic resonance examination showed no signs of late myocardial gadolinium enhancement. The clinical picture and course of the disease was consistent with TS. Consequently, we describe for the first time a case of TS triggered by myocardial ischemia caused by BICS. Furthermore, our case and sufficient supporting data from the literature demonstrate that acute coronary syndrome is an important and frequent but up till now missed trigger factor for TS.

Coronary microvascular dysfunction in Takotsubo syndrome: cause or consequence.

Takotsubo syndrome (TS) is an acute cardiac disease entity, characterized by a transient myocardial stunning in a distinctive predominantly regional circumferential pattern. One of the discussed pathological mechanisms of TS is coronary ischemia including coronary microvascular dysfunction (CMVD). Many studies have revealed invasive or non-invasive signs of CMVD in patients with TS, and therefore some investigators believe that CMVD is the primary cause of TS. Nevertheless, other studies have not shown any sign of CMVD. In addition, those studies, which have shown signs of CMVD, do not reveal such signs in all the three coronary vessel distribution; some of the patients show signs of CMVD in two or only one coronary artery territory. Moreover, signs of CMVD in TS are more prevalent and more pronounced in the left anterior descending artery (LAD) distribution. The CMVD in TS is reversible in a pattern parallel to the improvement of myocardial wall motion abnormality. In this review, substantial evidences challenging CMVD as the primary cause of TS and supporting the concept that CMVD is a secondary or epiphenomenon in TS are provided. Furthermore, convincing explanation is given for the causes of the more prevalent and the more pronounced signs of CMVD observed in the LAD distribution.