Editorial

Acute myocardial infarction with normal coronary arteries: Role of coronary artery spasm and arrhythmic complications

The Cardiovascular Disease in Women Committee of the American College of Cardiology convened a working group to develop a consensus regarding the continuing rise of mortality rates in young women aged 35 to 54 years. Heart disease mortality rates in young women continue to increase. Young women have increased mortality secondary to ischemic heart disease (IHD) compared with comparably aged men and similar mortality to that observed among older women. The authors reviewed the published evidence, including observational and mechanistic/translational data, and identified knowledge gaps pertaining to young women. This paper provides clinicians with pragmatic, evidence-based management strategies for young women at risk for IHD. Next-step research opportunities are outlined. This report presents highlights of the working group review and a summary of suggested research directions to advance the IHD field in the next decade.

L’échocardiographie à la dobutamine (EDS) est utilisée de façon courante comme un test non invasif d’ischémie indépendant de l’effort et visant à détecter la présence d’une atteinte coronaire et pour évaluer l’étendue de l’ischémie myocardique. Elle peut cependant être associée à du spasme coronaire. Dans cette étude, notre objectif est d’évaluer la prévalence et les facteurs prédictifs de spasme coronaire lié à la dobutamine chez les patients sans coronaropathie connue et avec des EDS faussement positives (test positif mais sans lésions coronaires significatives à la coro).

Trois mille neuf cent cinquante-deux patients ayant bénéficié d’EDS dans notre laboratoire d’échographie entre janvier 2010 et mai 2012 ont été prospectivement évalués. Ceux avec une EDS positive ont bénéficié de coronarographies avec injection de méthylergotamine en cas d’absence de lésions coronaires ou de vasospasme spontané sévère. Les patients avec un spasme spontané sévère ou un test à la méthylergometrine positif mais sans lésions coronaires ont été inclus et comparés à ceux avec EDS positives mais sans lésions coronaires ni spasme (« vrais » faux positifs).

Vingt-neuf patients avec spasme (19,4 % des EDS positives sans histoire coronaire) ont été comparés avec 56 patients sans lésions ni spasme (« vrais » faux positifs). Ils étaient plus souvent fumeurs (72,4 % vs 37,5 % ; p = 0,003) ; avaient plus souvent une dyslipidémie (79,3 % vs 43 % ; p = 0,001) ; ils avaient une aire ischémique en pic de stress plus importante (3,4 segments vs 2,7 segments ; p = 0,05). En analyse multivariée, la dyslipidémie (HR = 10,7 ; 95 % CI = [2,7–42,1] ; p = 0,001) et le tabagisme actif (HR = 6,1 ; 95 % CI = [1,7–21,1] ; p = 0,004) étaient les facteurs prédictifs indépendants de spasme coronaire plutôt que de « vrais » faux positifs.

Le spasme coronaire lié à la dobutamine est présent chez une proportion significative des patients étiquetés faux positives et devraient systématiquement être recherchés. La dyslipidémie et le tabagisme actifs sont les 2 facteurs prédictifs indépendants de spasme plutôt que de fausse positivité.

Dobutamine stress echocardiography (DSE) is being consistently used as an exercise-independent stress modality aimed at the detection of coronary artery disease (CAD) and the evaluation of myocardial ischemia. It may though occasionally induce coronary vasospasm. In this study, we aimed to evaluate the prevalence and predictors of dobutamine-related coronary spasm in patients without known CAD and false positive DSE (positive DSE but no significant coronary lesions on angiogram).

Three thousand nine hundred and fifty-two patients referred to our echocardiography laboratory for DSE between January 2010 and May 2012 were prospectively investigated. Those with positive DSE underwent coronary angiograms with systematic methylergometrine intracoronary injection in case of absence of significant coronary stenosis or spontaneous occlusive coronary spasm. Patients with spontaneous occlusive coronary spasm or positive methylergometrine test but no significant stenoses were enrolled and compared with those with positive DSE but no coronary lesions nor spontaneous or induced spasm (“true” false positive DSE).

Twenty-nine patients with DSE-related vasospasm (19.4% of positive DES without known CAD) were compared with 56 patients with no lesions and no spasm (“true” false positive DSE). They were more frequently smokers (72.4% vs 37.5%; P = 0.003); they had more frequently dyslipidemia (79.3% vs 43%; P = 0.001); they also had a larger ischemic area at peak DSE (3.4 segments vs 2.7 segments; P = 0.05). On multivariate analysis, dyslipidemia (HR = 10.7; 95% CI = [2.7–42.1]; P = 0.001) and active smoking (HR = 6.1; 95% CI = [1.7–21.1]; P = 0.004) were found to be independent predictors of spasm-related DSE rather than “true” false positive DSE.

DSE-related coronary spasm is present in a significant proportion of patients with erroneously labelled “false” positive DSE and should systematically be ruled out. Dyslipidemia and active smoking were independent predictors of spasm rather than “true” false positive DSE.

The purpose of this study was to determine if cholesterol crystals can injure the endothelial surface by their jagged edges altering vasoreactivity and contributing to no-reflow after intervention.

After plaque rupture, cholesterol crystals are released into the circulation and flow downstream contacting the arterial wall.

Both carotid arteries from 22 rabbits were placed in a dual perfusion chamber and challenged with norepinephrine followed by acetylcholine and nitroprusside. Arterial diameters were measured before and after exposure to cholesterol crystals or microspheres and compared with diameters of normal control arteries. Arteries were examined by light, confocal, atomic force and scanning electron microscopy.

Pre-exposure mean arterial diameter was 2.33 ± 0.27 mm. With baseline norepinephrine there was vasoconstriction of 0.82 ± 0.19 mm, 0.79 ± 0.18 mm, and 0.83 ± 0.16 mm in lumen diameter in the crystal, microsphere, and control groups, respectively. After cholesterol crystals or microspheres, vasoconstriction was significantly less for cholesterol crystals but not for microspheres (0.71 ± 0.28 mm and 0.81 ± 0.15 mm; p < 0.02 and p = 0.68). After acetylcholine in the same artery, there was significantly less dilation before versus after crystals (0.49 ± 0.24 mm vs. 0.38 ± 0.22 mm, p = 0.04) but not with microspheres or in the control group. There was no significant difference after nitroprusside in any group, suggesting endothelial injury. By scanning electron microscopy, cholesterol crystals were found embedded in the intima with endothelial cell tears whereas the microsphere treatment and control groups had minimal or no injury (93% vs. 31% vs. 14%; p < 0.01). By atomic force microscopy, surface roughness was significantly greater with cholesterol crystals compared with microspheres or in control arteries (p < 0.05).

Cholesterol crystals damaged the endothelium and reduced vasodilator response, potentially aggravating myocardial ischemia after interventions.

The pathogenetic mechanism of premature myocardial infarction (MI) remains unknown. We explored the association of homocysteine and its main genetic modulator methylenetetrahydrofolate reductase (MTHFR) 677C->T polymorphism with the development of MI ≤35 years of age.

We performed a case-control study of 147 patients with a first MI ≤35 years and 103 age and sex-matched controls. We assessed plasma lipids, homocysteine, folate, vitamin B₁₂ levels and MTHFR 677C->T polymorphism.

Patients with premature MI had higher homocysteine levels (13.9 ± 8.6 vs. 11.8 ± 4.9 mmol/l, p = 0.02) and higher prevalence of TT homozygocity compared to controls (27.1% vs. 14.6%, p = 0.02). Thirty-four patients (23.6%) had angiographically “normal” coronary arteries. Subgroup analysis according to angiographic findings (“normal” coronary arteries versus significant coronary heart disease) showed that only patients with MI and “normal” coronary arteries (MINCA) had higher homocysteine levels compared to controls (17.6 ± 12.2 vs. 11.8 ± 4.9 mmol/l, p < 0.001). The prevalence of TT genotype was higher only in patients with MINCA compared to controls (44.1% vs. 14.6%, p = 0.001) (odds ratio 4.6, 95% confidence interval (CI), 1.9–11, p = 0.001). This association remained after adjusting for conventional risk factors (odds ratio 3.4, 95% CI, 1.1–10.4, p = 0.03). The adjusted odds ratio for MINCA of young individuals with MTHFR TT genotype and folate levels in the lowest quartile (≤5 ng/ml) was 6.1 (95% CI, 1.1–31, p = 0.04).

Homozygocity for the 677C->T mutation of MTHFR is independently associated with the development of premature MINCA.

Normal coronary arteries were found in 22 (5.8%) of 379 patients presented with acute inferior myocardial infarction. These patients were significantly younger, had less cardiovascular risk factors, better systolic heart function, and lower cardiac enzymes level. Electrocardiography significantly showed more (1) ratio of ST-segment elevation in II/ III ≥ 1; (2) isoelectric ST-segment in I; (3) ST-segment elevation in I; and less (4) paroxysmal atrial fibrillation; (5) ST-segment depression in I; and (6) ST-segment elevation in V4R. In conclusion, this subset of patients had clinical features suggestive of smaller infarct size compared with those suffering from atherosclerotic disease. They may have more left circumflex artery involvement and distal right coronary artery occlusion, as deduced from electrocardiography.