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.

Myocardial contrast echocardiography yields best accuracy using quantitative analysis of digital data from pulse inversion technique: comparison with second harmonic imaging and harmonic power Doppler during simultaneous dipyridamole stress SPECT studies.

AIMS: This prospective study assesses the (1) feasibility of quantifying ultrasound myocardial perfusion studies based on the densitometric analysis of digital data and the (2) comparison of pulse inversion, second harmonic and harmonic power Doppler modalities with SPECT. METHODS AND RESULTS: Twenty-three patients with suspected ischaemic heart disease had i.v. injections of Tc-Sestamibi and Optison during a dipyridamole stress test for echocardiography in pulse inversion, second harmonic and harmonic power Doppler mode. Analysis was (a) visual by scoring and (b) quantitative by densitometry of digital data for background subtracted myocardial opacification (a.u.) and normalized contrast effect (%). In the nine control patients, myocardial opacification at stress was greater (P< or =0.002) than in the pathologic group (5. +/- 3.3 vs 2.6 +/- 2.5 a.u. in pulse inversion, 5.4 +/- 2.1 vs 2.4 +/- 1.8 in second harmonic and 7.1 +/- 3.7 vs 4.9 +/- 3.7 a.u. in harmonic power Doppler). In the pathologic group, normalized contrast effect decreased significantly during stress (23.7 +/- 18.8 to 11.3 +/- 10.8%, P<0.003) only in pulse inversion. Kappa values for patient based diagnostic agreement with SPECT were 0.75 by pulse inversion, 0.62 by second harmonic and 0.52 by harmonic power Doppler for quantitative analysis, and 0.51, 0.37 and 0.35 respectively, for visual assessment. CONCLUSION: Myocardial contrast echocardiography should be analysed using densitometry of digital data. The new technique pulse inversion demonstrates best agreement with SPECT data.

Organization and development of the perivascular space system in the neurohypophysis of the laboratory mouse.

The organization of the system of perivascular space around the capillaries in the neurohypophysis was studied in the adult and developing laboratory mouse by the use of histological silver impregnation and electron microscopical techniques. In the median eminence short and long extensions, arising mainly from the shallow space around capillary loops of the primary plexus of the portal system, formed radiations into the adjacent neural tissue of the external zone. The tissue of the neural lobe was separable into non-vascular regions dominated by undilated portions of neurosecretory nerve fibres and pituicytes, and neurovascular regions with perivascular space extensions forming an extensive system of connections between neighbouring capillaries. In the median eminence, the system of extensions of the perivascular space was estimated to increase the neurovascular contact surface area by at least 50%, implying an increased efficiency of the organ without a notable increase of its volume. The possibility that the ramifications of the perivascular space imply an enhanced uptake rate into the bloodstream and a subsequent increased concentration of the neurohormones in the portal blood, was discussed. During development of the median eminence, differentiation of perivascular space extensions of the adult type started in the juvenile of about three weeks of age, when shallow capillary loops had been formed. In the neural lobe, perivascular space ramifications were already present when the internal capillaries were formed and were fairly frequent in ten-day young. At the age of three to four weeks the organization of the system was similar to that of the adult animal.

An electron microscope study of the differentiating capillaries of the mouse neurohypophysis.

The developing capillaries of the mouse neurohypophysis were studied in the electron microscope to elucidate the fine structural differentiation of the vascular component of the neuro-hemal contact zones in the external median eminence and the neural lobe. In the embryo the growth of the superficial net of the primary plexus of the hypophysial portal system is largely manifested by the presence of proliferation areas located within the capillary plexus covering the surface of the median eminence. Presumptive shallow capillary loops diverge from these ares in the first postnatal week. Differentiation of the capillary wall follows the pattern outlined for continuous capillaries. A few fenestrae appear in the endothelium of immature, superficial vessels at the 17th gestational day, increase in frequency during the following embryonic days, and occur regularly in the postnatal animal. In the neural lobe the internal capillaries proliferative by vascular sprouts emanating from the vessels on the surface of the gland. At the end of embryonic time an extensive net has developed, composed of capillaries with immature characteristics. Proliferation is largely finished by the end of the third postnatal week, when mature capillaries dominate the picture. Formation of attenuated, porous areas is a postnatal process, apart from single fenestrae appearing in the walls of a few immature capillaries in late fetal life. The structural possibilities for an onset of neurohypophysial function in the mouse is discussed.

Electron microscope studies on the intermediate lobe of the embryonic mouse.

The development of the intermediate lobe of the hypophysis was studied in the embryonic C3H mouse; at least four glands from embryos of every gestational day from 15 to 19 were examined. In the 16 day-old embryo prospective secretory cells proliferate at the centre of the intermediate lobe anlage. At the same stage cylindrical cells bordering the hypophyseal cleft begin to reorganize into marginal cells. By the end of fetal life marginal cells are well differentiated. In the 17 day-old embryo a few granular inclusions appear in some centrally located cells. Secretory cells increase in number during the following two embryonic days. Some of these cells contain polymorphic populations of granular and vesicular inclusions by gestational day 19. The possibility of a dual formation of secretory inclusions is discussed. The result implies that the onset of granule-formation by these cells is not contemporaneous with the start of production of melanophore-expanding substances, the presence of which has been detected by earlier biological assays.