The value of a new cardiac magnetic resonance imaging protocol in Myocardial Infarction with Non-obstructive Coronary Arteries (MINOCA) - a case-control study using historical controls from a previous study with similar inclusion criteria.

BACKGROUND: Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is common with a prevalence of 6% of all patients fulfilling the diagnosis of myocardial infarction. MINOCA should be considered a working diagnosis. Cardiac Magnetic Resonance (CMR) imaging has recently been suggested to be of great value to determine the cause behind MINOCA. The objectives of this paper are to describe the rationale behind the second Stockholm Myocardial Infarction with Normal Coronaries (SMINC-2) study and to discuss the protocol for investigation of MINOCA patients in the light of the recently published position paper from the European Society of Cardiology. METHODS: The SMINC-2 study is an open non-randomised study using historical controls for comparison. The primary aim is to prove that MINOCA patients investigated with the latest CMR imaging technique can achieve a diagnosis in 70% of all cases entirely by imaging. By including 150 patients we will have >80% chance to prove that the diagnostic accuracy can be improved by 20 absolute % with a p-value of less than 0.05 when compared with CMR imaging in the SMINC-1 study. Furthermore, in addition to invasive coronary angiography, coronary arteries are evaluated by computed tomography angiography to investigate coronary causes and questionnaires are used to describe Quality-of-Life (QoL). By January 1st 2017, 75 patients have been included. DISCUSSION: Whether CMR imaging can provide a diagnosis to an adequate proportion of MINOCA patients is unknown. Well-defined inclusion and exclusion criteria will be used to compare a MINOCA cohort from the population with an appropriate control group. Positive results are likely to influence future guidelines of the management of MINOCA. Furthermore, the study will give mechanistic insights into MINOCA in particular in patients with "true" myocardial infarction and describe QoL in this vulnerable group of patients. TRIAL REGISTRATION: Clinical Trials NCT02318498 .

Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study.

OBJECTIVES: Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients. DESIGN: The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study. SETTING: Coronary care units in the Stockholm metropolitan area. SUBJECTS: Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded. RESULTS: In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 6-28) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified. CONCLUSION: In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.

Risk factors for myocardial infarction with normal coronary arteries and myocarditis compared with myocardial infarction with coronary artery stenosis.

The interest and awareness of myocardial infarction with normal coronary arteries (MINCA) have increased recently due to the frequent use of coronary angiography, the description of Takotsubo stress cardiomyopathy, and new sensitive troponin analyses. The prevalence of MINCA in all patients with myocardial infarction (MI) was registered during a 3-month period in the Stockholm metropolitan area in Sweden. The results showed that MINCA is more common than previously thought (7%) and affecting one third of every woman with MI. Patients with myocarditis were younger and more often presented with signs of inflammation such as elevated C-reactive protein and fever. Myocarditis constitutes an important differential diagnosis for coronary artery disease. There is a need for larger studies of MINCA, including investigation with cardiac magnetic resonance imaging, to establish prevalence and pathological process in this important subgroup of MI.

Myocardial infarction with angiographically normal coronary arteries.

Myocardial Infarction with Normal Coronary Arteries (MINCA) is an important subgroup of myocardial infarction with a frequency of at least 3-4% of all myocardial infarctions. The interest and awareness of MINCA have increased recently due to the frequent use of coronary angiography, the description of Takotsubo stress cardiomyopathy and new sensitive troponin assays. Since myocarditis may mimic myocardial infarction it is essential to exclude this in patients with myocardial infarction with angiographically normal coronary arteries. Cardiac magnetic resonance imaging is a cornerstone not only to establish the diagnosis but also an important tool in the search for different causes of myocardial damage. In the future, atherosclerotic burden, hemostatic function, characterization of stressors and inflammation will be important targets for research in this group of patients.

Continuous haemodynamic monitoring during withdrawal of diuretics in patients with congestive heart failure.

AIMS: Right heart pressure parameters can be recorded continuously with the help of an implanted haemodynamic monitor. The aim of this study was to investigate the usefulness of the device in adjusting diuretic medication in patients with chronic congestive heart failure, and to evaluate the response of right ventricular pressure to increased volume load induced by diuretic withdrawal. METHODS AND RESULTS: Four patients with stable congestive heart failure were implanted with an implantable haemodynamic monitor. Furosemide, the only diuretic used, was reduced by 50% the first week, withdrawn completely for the second week and then reinstituted in the initial dose. Right ventricular systolic and diastolic pressure, pulse pressure, dP/dt, estimated diastolic pulmonary artery pressure and heart rate were sampled continuously. Patients were evaluated by body weight, NYHA class, serum creatinine, serum brain natriuretic peptide, the 6 min walk test, quality of life and echocardiography on days 0, 7, 14 and 21. We observed significant changes in right ventricular pressure parameters in parallel with clinical signs and symptoms of worsening heart failure, such as increased body weight, a shorter walking distance and impaired quality of life. Moreover elevated levels of brain natriuretic peptide and lower creatinine levels were observed. CONCLUSION: Haemodynamic changes due to increased volume load can be detected with an implantable haemodynamic monitor. Such data provide useful information for tailoring an optimal diuretic dose in patients with congestive heart failure.

Chronic cobalt exposure affects antioxidants and ATP production in rat myocardium.

Chronic cobalt exposure is characterized by severe cardiac insufficiency. Since the mechanisms of cobalt toxicity are not yet clear, we analysed the effects of chronic cobalt exposure on antioxidant enzyme activities and myocardial mitochondrial ATP production rate in a rat model. One group of rats was fed a conventional diet and another a cobalt supplemented diet for 24 weeks. The manganese-superoxide dismutase activity was markedly reduced in the cobalt rats (18+/-4.7 U/mg protein) compared to the control rats (100+/-22 U/mg protein; p <0.001). Activity in the respiratory chain enzymes succinate-cytochrome c reductase, NADH-cytochrome c reductase and cytochrome c oxidase was also reduced in the cobalt rats (p<0.01). Glutamate dehydrogenase activity, located in the mitochondrial matrix, was unchanged. The mitochondrial ATP production rate in relation to myocardial mass was lower in the cobalt rats for all substrates tested except palmitoyl-l-carnitine + malate. In conclusion, 24 weeks of chronic cobalt exposure induces a marked decrease in manganese-superoxide dismutase activity, a moderate decrease in mitochondrial ATP production rate and a general reduction in the capacity of the respiratory chain. The impairment in mitochondrial ATP production might be secondary to the decreased manganese-superoxide dismutase activity, causing inactivation of mitochondrial factors susceptible to superoxide radicals.

Myocardial morphology and cardiac function in rats with renal failure.

The effects of chronic renal failure on cardiac performance and myocardial morphology were studied in rats: 17 with 5/6 nephrectomy (CRF rats) and 12 with sham operation (controls). Cardiac function was assessed 8 weeks postoperatively, using the Langendorff technique for an isolated working heart model. After the hemodynamic study the hearts were fixed for electron and light microscopy. In the CRF rats left ventricular systolic pressure was significantly higher at all preloads (10-20 cmH2O) and afterloads (70-90 cmH2O), and left ventricular stroke work was significantly increased at preload 20 cmH2O with afterloads 70 or 90 cmH2O. Light microscopy revealed fibronecrotic lesions consisting of fibroblastic proliferation with newly formed collagen interposed between or entrapping degenerative myocytes. The changes were focally distributed, with perivascular accentuation and were most frequent in the basal half of the ventricular wall. Electron microscopy of non-necrotic myocytes showed intact myocytes, with mitochondria morphometrically similar in the 2 groups, but a significantly lower incidence of mitochondrial granules in the CRF rats. Thus 8 weeks of CRF showed no cardiac dysfunction associated with the focally distributed fibronecrotic myocardial lesions and decrease in mitochondrial granules. The precise mechanism of the discrepancy between the morphological change and the cardiac function is unclear. One possible explanation may be that because the pathological changes in the myocardium were focal or mild to moderate, some compensation mechanism may be involved or it may be the turning point of functional change from acute renal failure to the chronic state.

Two-year results of a controlled study of residential rehabilitation for patients treated with percutaneous transluminal coronary angioplasty. A randomized study of a multifactorial programme.

AIMS: In a multifactorial lifestyle behaviour programme, of 2 years duration, to study the maintenance of achieved behaviour and risk factor-related changes. METHODS AND RESULTS: Out of a consecutive population of 151 patients treated with percutaneous transluminal angioplasty under 65 years of age, 87 were randomly allocated to an intervention group (n=46) or to a control group (n=41). The programme started with a 4 week residential stay, which was focused on health education and the achievement of behaviour change. During the first year of follow-up, a maintenance programme included regular contacts with a nurse, while no further rehabilitative efforts were offered during the second year. One patient died (control). During the second year the proportion of hospitalized patients was lower in the intervention group (4% vs 20%;P<0.05). Patients in the intervention group improved several lifestyle dependent behaviours: diet (index at 0, 12 and 24 months): 10.5+/-3. 4, 12.9+/-2.5 and 12.4+/-2.6 in the intervention group (I) vs 10. 1+/-3.2, 10.7+/-3.0 and 11.8+/-3.2 in the control group (C);P<0.05, exercise sessions per week: 2.5+/-2.3, 4.5+/-1.9 and 4.4+/-2.1 (I) vs 3.1+/-2.2, 3.5+/-2.3 and 3.7+/-2.7 (C);P<0.05, and smoking; 18%, 6% and 9% (I) vs 12%, 21% and 18% (C);P<0.05. This corresponded to improvement in exercise capacity (0, 12 and 24 months): 156+/-42, 174+/-49 and 165+/-47 W (I) vs 164+/-40, 163+/-49 and 156+/-48 watts (C);P<0.05. There were no significant differences between the two groups with regard to serum cholesterol levels at 0 and 24 months: 5. 4+/-0.8 and 5.2+/-0.9 mmol. l(-1)(I) vs 5.4+/-1.0 and 4.9+/-0.9 mmol. l(-1)(C); ns, low density lipoprotein cholesterol level: 3.6+/-0.8 and 3.4+/-0.8 mmol. l(-1)(I) vs 3.7+/-0.9 and 3.3+/-0.7 mmol. l(-1)(C); ns, triglyceride level: 2.2+/-1.6 and 1.8+/-1.3 mmol. l(-1)(I) vs 2.2+/-1.4 and 1.6+/-0.6 mmol. l(-1)(C); ns, body mass index (0, 12 and 24 months): 27.5+/-4.5, 27.0+/-4.3 and 27.4+/- 4.5 kg. m(-2)(I) vs 26.8+/-2.8, 26.9+/-2.7 and 26.9+/- 3.2 kg. m(-2)(C); ns, waist/hip ratio or blood pressure. The two groups did not differ in quality of life, or psychological factors. Return to work after 12 and 24 months was 74% and 78% (I) vs 68% and 61% (C); ns. CONCLUSION: This rehabilitation programme influenced important lifestyle behaviour and reduced some, but not all, important risk factors

Multifactorial evaluation of a program for lifestyle behavior change in rehabilitation and secondary prevention of coronary artery disease.

A comprehensive, multifactorial lifestyle behavior change program was developed for rehabilitation and secondary prevention of subjects with coronary artery disease. The purpose of the present report is to describe this intervention model and to analyze results achieved in a first group of consecutive participants. Main inclusion criteria for the 292 subjects were a recent history of acute myocardial infarction, coronary artery bypass surgery, or percutaneous transluminal coronary angioplasty. The program commenced with a 4-week residential stay, with the focus on health education and the achievement of behavior change in major lifestyle areas. During the year of follow-up a systematic maintenance program included regular contact with a nurse. Morbidity and mortality was low. Self-reported quality of life improved and there were significant improvements in blood lipids, exercise capacity and body mass index. There were also significant changes both in psychological variables such as Type A behavior, anger, hostility, and in major lifestyle areas such as stress reactions, diet, exercise and smoking. These changes compared favorably with data from relevant samples from the Swedish normal population. This program had a considerable effect on a number of important factors for rehabilitation and secondary prevention of coronary artery disease.

Behavioral effects of a comprehensive, multifactorial program for lifestyle change after percutaneous transluminal coronary angioplasty: a prospective, randomized controlled study.

A group of 93 coronary patients recently treated with percutaneous transluminal coronary angioplasty (PTCA) were randomly assigned to either an intervention or a control group. Subjects in the intervention group participated in a comprehensive behaviorally oriented program aimed at achieving significant long-term changes in risk factor-related lifestyle behavior. Assessments of lifestyle behaviors, psychological factors, biological risk factors, and rehabilitation as well as secondary prevention endpoints were carried out, at inclusion and after 12 months. Results showed that the intervention patients, as compared with controls, improved significantly on measures assessing smoking, exercise, and diet habits. These self-rated changes were confirmed by weight reductions and improved exercise capacity, as well as by between-group differences in subclinical chest pain during an exercise test. However, few effects were found on the different psychological variables, as well as on morbidity or return to work.

Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group.

Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 +/- 10 years, ejection fraction at rest was 22% +/- 10%, and maximal exercise tolerance was 91 +/- 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% +/- 12% versus 23% +/- 12% (NS), 25% +/- 13% versus 23% +/- 12% (P < .05), and 23% +/- 11% versus 22% +/- 11% (NS). Maximal exercise capacity increased from 94 +/- 31 W during the placebo period to 100 +/- 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 +/- 23 during the placebo period to 113 +/- 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.

Acute cobalt exposure and oxygen radical scavengers in the rat myocardium.

Excessive amounts of cobalt are cardiotoxic, although the mechanism for this toxicity remains unclear. We studied the effects of acute cobalt exposure on the activities of free radical scavengers in the myocardium in 5 groups of rats. Six rats served as a control group and were given a daily subcutaneous injection of 1 ml saline for 8 days. The other 4 groups of rats received a daily injection subcutaneously of cobalt chloride in doses of 1 mg/kg bw, 5 mg/kg bw, 20 mg/kg bw and 50 mg/kg bw, respectively for 8 days. There was a marked and dose-dependent accumulation of cobalt in the myocardium of the cobalt exposed rats. Creatine kinase, copper-zinc superoxide dismutase (CuZn-SOD) and alpha-tocopherol content did not differ between the control and the cobalt exposed groups. The activity of glutathione peroxidase increased, while the activity of manganese-superoxide dismutase (Mn-SOD) was significantly reduced in the cobalt exposed groups. There was an inverse relationship (r = 0.60, P < 0.0001) between the cobalt content and Mn-SOD activity in the myocardium. These results suggest that acute cobalt cardiotoxicity may involve a reduction of intrinsic scavengers resulting in an increased vulnerability to oxygen free radical toxicity.