There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

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.

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

Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome, myocardial infarction, and sudden death, particularly among young women and individuals with few conventional atherosclerotic risk factors. Patient-initiated research has spurred increased awareness of SCAD, and improved diagnostic capabilities and findings from large case series have led to changes in approaches to initial and long-term management and increasing evidence that SCAD not only is more common than previously believed but also must be evaluated and treated differently from atherosclerotic myocardial infarction. High rates of recurrent SCAD; its association with female sex, pregnancy, and physical and emotional stress triggers; and concurrent systemic arteriopathies, particularly fibromuscular dysplasia, highlight the differences in clinical characteristics of SCAD compared with atherosclerotic disease. Recent insights into the causes of, clinical course of, treatment options for, outcomes of, and associated conditions of SCAD and the many persistent knowledge gaps are presented.

/pdf/spontaneous-coronary-artery-dissection-current-state-of-the-2tmhkoj05i.pdf

Spontaneous Coronary Artery Dissection: Current State of the Science: A Scientific Statement From the American Heart Association.

Background— Catheter-based intracoronary vascular endothelial growth factor (VEGF) gene transfer is a potential treatment for coronary heart disease. However, only limited data are available about local VEGF gene transfer given during angioplasty (PTCA) and stenting. Methods and Results— Patients with coronary heart disease (n=103; Canadian Cardiovascular Society class II to III; mean age, 58±6 years) were recruited in this randomized, placebo-controlled, double-blind phase II study. PTCA was performed with standard methods, followed by gene transfer with a perfusion-infusion catheter. Ninety percent of the patients were given stents; 37 patients received VEGF adenovirus (VEGF-Adv, 2×1010 pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 μg of DNA with 2000 μL of DOTMA:DOPE [1:1 wt/wt]), and 38 control patients received Ringer’s lactate. Follow-up time was 6 months. Gene transfer to coronary arteries was feasible and well tolerated. The overall clinical restenosis rate was 6%. In quantitati...

Safety and Feasibility of Catheter-Based Local Intracoronary Vascular Endothelial Growth Factor Gene Transfer in the Prevention of Postangioplasty and In-Stent Restenosis and in the Treatment of Chronic Myocardial Ischemia Phase II Results of the Kuopio Angiogenesis Trial (KAT)

Myocardial infarction in the absence of obstructive coronary artery disease is found in ≈5% to 6% of all patients with acute infarction who are referred for coronary angiography. There are a variety of causes that can result in this clinical condition. As such, it is important that patients are appropriately diagnosed and an evaluation to uncover the correct cause is performed so that, when possible, specific therapies to treat the underlying cause can be prescribed. This statement provides a formal and updated definition for the broadly labelled term MINOCA (incorporating the definition of acute myocardial infarction from the newly released "Fourth Universal Definition of Myocardial Infarction") and provides a clinically useful framework and algorithms for the diagnostic evaluation and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.

Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association

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.

/pdf/epidemiology-pathogenesis-and-management-of-takotsubo-3w5ndtbs7f.pdf

Epidemiology, pathogenesis, and management of takotsubo syndrome.

Myriads of physical stress factors including pheochromocytoma have been reported triggering takotsubo syndrome (TS). The aim of this study was to report on the clinical features and outcome of pheochromocytoma-induced TS (Pheo-TS) in a large cohort of patients. Eighty published cases of Pheo-TS were retrieved from the literature and compared with 1,750 cases of all patients with TS (All-TS) published recently by Templin et al. Patients with Pheo-TS were on average 19.87 years younger than those with All-TS (p <0.0001). The women were still predominating in Pheo-TS but significantly in a lower percentage (70% in Pheo-TS vs 89.8% in All-TS, p <0.00001). Almost 1/3 (30%) of Pheo-TS cases had basal TS pattern compared with 2.2% of cases in All-TS (p <0.00001) and 1/5 (20%) had global TS compared with no cases in All-TS. Two thirds of Pheo-TS cases (67.9%) developed complications, which was significantly higher than complication rates in All-TS (21.8%), but there was no difference in the inhospital mortality between the 2 studies. The most important risk factors for the development of complications in Pheo-TS were age <50 years and global and basal TS localization patterns. The recurrence rate of 17.7% in Pheo-TS was significantly higher than the 3.26% in All-TS (p <0.00001). In conclusion, Pheo-TS is characterized by a dramatic clinical presentation with high complication rates and relatively high recurrence rate. Patients with Pheo-TS are significantly younger than All-TS. The TS localization pattern in Pheo-TS differed significantly from All-TS with basal pattern in almost 1/3 of cases and global pattern in 1/5 of the cases.

Clinical Features and Outcome of Pheochromocytoma-Induced Takotsubo Syndrome: Analysis of 80 Published Cases.

. Sarkar N, Ruck A, Kallner G, Y-Hassan S, Blomberg P, Islam KB, van der Linden J, Lindblom D, Nygren AT, Lind B, Brodin L-A, Drvota V, Sylven C (Karolinska Institute, Huddinge University Hospital, Novum, Stockholm, Sweden). Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease: 12-month follow-up. Angiogenic gene therapy. J Intern Med 2001; 250: 373–381.



Objective. To test the safety and bioactivity of phVEGF-A165 after intramyocardial injection during 12-month follow-up.



Design. Open-labelled study.



Subjects. Inclusion criteria were angina pectoris, Canadian Cardiovascular Society (CCS) class III–IV, unamenable to further revascularization, ejection fraction (EF) >30%, perfusion defects extending over >10% of the anterolateral left ventricle wall detectable with adenosine single photon emission computerized tomography (SPECT) and at least one patent vessel visible by coronary angiography. Seven of 39 patients referred for gene therapy were included.



Intervention. Via a mini-thoracotomy under general anaesthesia, phVEGF-A165 was injected directly into the myocardium at four sites in the anterolateral region of the left ventricle.



Results. Operative procedures were uneventful. Perioperative release of myocardial markers and electrocardiogram (ECG) changes were detected in two patients. There were no perioperative deaths but one patient died 7 months postoperatively because of myocardial infarction. Plasma vascular endothelial growth factor (VEGF)-A levels increased two to threefold peaking 6 days postoperatively (P < 0.004) and returning to baseline by day 30. A significant reduction in angina pectoris was reported. The CCS class improved from 3.3 ± 0.2 to 1.9 ± 0.3 (P < 0.01) and nitroglycerine intake decreased from 39 ± 15 to 12 ± 5 tablets week–1 (P < 0.001) 2 months after gene transfer. Improvements remained after 12 months when nitroglycerine consumption approached zero. Improved myocardial function in the phVEGF-A165 injection region was documented in all patients (P < 0.016) by tissue velocity imaging (TVI). Reduced reversible ischaemia was detected by adenosine SPECT in four patients. Improved collateralization was detected in four patients with coronary angiography.



Conclusion. Intramyocardial injection of phVEGF-A165 is safe and may lead to improved myocardial perfusion and function with longstanding symptomatic relief in end-stage angina pectoris. Based on these results this therapeutic potential is being tested in a double-blind placebo controlled multicentre trial, EUROINJECT ONE.

Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease – 12-month follow-up: Angiogenic gene therapy

Shams Y-Hassan

Papers

Epidemiology, pathogenesis, and management of takotsubo syndrome.

Clinical Features and Outcome of Pheochromocytoma-Induced Takotsubo Syndrome: Analysis of 80 Published Cases.

Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease – 12-month follow-up: Angiogenic gene therapy

Acute cardiac sympathetic disruption in the pathogenesis of the takotsubo syndrome: a systematic review of the literature to date.

Capecitabine caused cardiogenic shock through induction of global Takotsubo syndrome