Epicardial and microvascular coronary vasomotor dysfunction and its relation to myocardial ischemic burden in patients with non-obstructive coronary artery disease.

AIM: To assess the relative contribution of epicardial endothelium-dependent (EDD) and microvascular endothelium-independent (EIMVD) coronary vasomotor dysfunction to the extent of myocardial ischemia in patients with normal angiograms or non-obstructive coronary artery disease (NOCAD). METHODS: Coronary vasomotion was evaluated by quantitative angiography and blood flow (CBF) measurements during intracoronary acetylcholine, nitroglycerine, and adenosine in 101 patients. Myocardial SPECT ischemic burden was evaluated by semi-quantitative scoring of summed stress (SSS) and summed ischemic (SDS) perfusion defect size. RESULTS: Coronary vasomotor dysfunction was found in most patients (83; 77%) with a divergent behavior of EDD and EIMVD in one half of them (52.4%). There was no significant difference in SDS between patients with and without EIMVD, whereas SDS was significantly greater in subjects with EDD as compared to patients with normal response to acetylcholine (4.31 ± 2.44 vs 1.35 ± 1.45; P < .0001). Patients with EDD, either alone or in combination with EIMVD, had significantly higher SSS as compared to patients with lone EIMVD or normal vasomotor function (8.50 ± 5.32; 5.55 ± 3.21; 2.60 ± 2.14; and 1.74 ± 1.66, respectively; P < .0001). Acetylcholine CBF correlated inversely with both SDS (r = -0.545; P < .001) and SSS (r = 0.538; P < .001). CONCLUSIONS: In NOCAD patients with symptoms and signs of myocardial ischemia, vasomotor dysfunction is common. EDD is associated with greater extent of ischemia as compared to isolated EIMVD. Thus, assessment of both EIMVD and EDD is needed to recognize mechanisms of ischemia and identify patients with greater ischemic burden.

Abnormal coronary vasoreactivity in transient left ventricular apical ballooning (tako-tsubo) syndrome.

BACKGROUND: The exact etiology and pathophysiologic mechanisms of tako-tsubo syndrome (TTS) remain controversial. OBJECTIVE: To further evaluate the abnormal coronary vasoreactivity and its possible anatomical substrate in TTS. METHODS: We studied 47 patients (46 women; age 67±12years) who underwent diagnostic cardiac catheterization and evaluation of coronary vasoreactivity by sequential acetylcholine (Ach), nitroglycerine and adenosine testing with angiographic and intracoronary pressure-Doppler flow monitoring. Coronary artery wall morphology was also evaluated by intravascular ultrasound (IVUS) imaging in 45 vessels of 43 patients. RESULTS: Abnormal coronary vasoconstriction to Ach stimulation was elicited in 40 patients (85%) involving the LAD artery and its branches in 39 (83%). Abnormal microvascular function was seen in 39 (83%) patients. Overall, hyperemic microvascular resistance index (HMR) was higher and Doppler coronary flow velocity reserve (CFVR) was lower in the LAD artery territory as compared to the reference territories (2.64±1.23 vs 2.05±0.56; p=0.008 and 1.95±0.7 vs 2.3±0.6; p=0.018, respectively). IVUS revealed no plaque rupture, dissection or thrombosis but occult plaque formation and myocardial bridging were found as a possible anatomical substrate of endothelial dysfunction in 67% and 48.8% patients respectively. CONCLUSIONS: A global failure of coronary vasomotor function was demonstrated in most TTS patients. These findings implicate abnormal vasoconstrictive response to the activation of the sympathetic system as a potential mechanism involved in the pathogenesis of myocardial stunning in TTS. PERSPECTIVES: Competency in medical knowledge: Abnormal coronary vasoconstriction secondary to endothelial dysfunction may actively contribute to the clinical manifestation of acute coronary syndromes in patients with non-obstructive coronary disease. Translational outlook 1: TTS patients reveal a global failure of vasomotor function with both vasoconstrictive response to acetylcholine and increased hyperemic microvascular resistances in the territory of myocardial stunning. They may also show occult coronary atherosclerosis and myocardial bridging as the anatomic substrates of endothelial dysfunction. Translational outlook 2: The cardiac phenotype of TTS includes a high prevalence of coronary vasomotor disturbances. These findings implicate abnormal vasoconstrictive response to the activation of the sympathetic system as a potential mechanism involved in the pathogenesis of TTS in post-menopausal women. Thus, a systematic evaluation of coronary vasoreactivity could better characterize the syndrome.

Clinical role of post-angioplasty hyperemic microvascular resistances in chronic ischemic left ventricular dysfunction.

AIMS: To investigate the impact of hyperemic microvascular resistances (HMRs) on myocardial perfusion and contractility after percutaneous coronary intervention (PCI) in chronic ischemic left ventricular dysfunction (CILVD). METHODS: The current retrospective study included 48 patients with CILVD of the left anterior descending territory undergoing HMRs assessment before and after PCI with a dual-sensor intracoronary pressure-flow wire. The severity of resting myocardial underperfusion and contractile dysfunction of the left anterior descending territory was scored as summed rest score (SRS-T) by single photon emission tomography, wall motion score index (WMSI-T) and left ventricular ejection fraction (LVEF) by transthoracic echocardiography before PCI and after 3 months. Patients were divided into two groups according to the mean post-PCI HMRs. RESULTS: Mean post-PCI HMRs were 2.05 ±â€Š0.43 mmHg/cm/s; increased HMRs (i.e. >2 mmHg/cm/s) were found in 17 patients (35.4%, group B) (3.29 ±â€Š0.77 mmHg/cm/s), whereas 31 patients (64.6%, group A) showed lower values (1.35 ±â€Š0.34 mmHg/cm/s; P < 0.001). Pre-PCI HMRs, WMSI-T and SRS-T were similar among groups.After PCI, a significant improvement of LVEF, WMSI-T and SRS-T was observed only in group A (6.6 ±â€Š7.4%, 0.44 ±â€Š0.42 and 3.9 ±â€Š2.9, respectively) compared with group B (1.3 ±â€Š1.9%, 0.02 ±â€Š0.07 and 1.1 ±â€Š1.9; P = 0.011, P < 0.001 and P = 0.028, respectively).Post-PCI HMRs predicted the absence of improvement of LVEF and WMSI-T at a cutoff value of 1.95 mmHg/cm/s (area under the curve 0.69 and 0.73; P = 0.038 and 0.017, respectively), with a positive predictive value of 96 and 100%, respectively. CONCLUSION: Increased post-PCI HMRs may predict the lack of functional improvement of the revascularized myocardium in CILVD.

A mathematical model for the vessel recruitment in coronary microcirculation in the absence of active autoregulation.

This paper proposes a mathematical model for vessel recruitment in the microvascular coronary network. The model is based on microvascular network units (MVNUs), where we define a MVNU as a portion of the microvascular network comprising seven generations of identical, parallel-arranged vessels (upstream arteries, large and small arterioles, capillaries, small and large venules, and downstream veins). The model implements a new mechanism to describe the variation in the number of MVNU in response to sudden variations of the local input pressure. In particular, it describes a recruitment mechanism dependent on distal pressure which operates in the coronary microcirculatory network even in maximally dilated conditions. We apply the model to interpret data from 29 patients who underwent revascularization by percutaneous coronary intervention (PCI). Treated vessels were the left anterior descending coronary artery, the left circumflex and the right coronary artery in 26, 2 and 1 patients, respectively. Following intracoronary adenosine administration, distal coronary pressure and blood flow were 48 ± 18 mmHg and 45 ± 30 ml/min before PCI, respectively, and significantly increased afterwards to 80 ± 17 mmHg and 68 ± 32 ml/min (p<0.001). The model predicts an increase in MVNU number in patients with preserved wall motion in the myocardial region which underwent PCI. On the contrary, a decrease in MVNU number is predicted by the model in patients with regional dysfunction and implies a relatively lower response of maximal flow to revascularization.

Larger perfusion defects with exercise compared with dipyridamole SPECT (exercise-dipyridamole mismatch) may reflect differences in epicardial and microvascular coronary dysfunction: when the stressor matters.

BACKGROUND: Previous studies have reported larger myocardial perfusion defects with exercise as compared with dipyridamole. The aim of this study was to assess the hypothesis that this mismatch may reflect differences in epicardial and microvascular coronary vasomotor function. METHODS AND RESULTS: The response to intracoronary acetylcholine, nitroglycerin, and adenosine was studied in 36 patients with suspected angina and normal or near-normal coronary angiography findings who underwent both exercise and dipyridamole perfusion imaging. Of the patients, 27 (75%) had reversible defects with exercise (group I) and 9 had normal scans or nonreversible defects (group II). Repeated imaging with dipyridamole showed significant improvement or disappearance of perfusion defects in group I patients. The mean summed difference score (SDS) decreased from 5.52 +/- 3.19 with exercise to 1.11 +/- 1.60 with dipyridamole (P = .0001) in group I and did not change in group II. An abnormal epicardial response to acetylcholine, reflecting endothelial dysfunction, occurred in 93% of group I patients compared with only 33% of group II patients (chi(2) = 9.46, P = .002) and was significantly related to exercise SDS (r = 0.49, P = .002) but not to dipyridamole SDS. By contrast, most patients showed normal epicardial and microvascular responses to the mainly non-endothelium-dependent vasodilators nitroglycerin and adenosine with no differences in coronary flow reserve between groups (2.91 +/- 0.72 vs 2.98 +/- 0.52, P = .79). CONCLUSIONS: Exercise-dipyridamole perfusion mismatch may reflect differences in epicardial endothelial and microvascular dysfunction.

Performing versus deferring coronary angioplasty based on functional evaluation of vessel stenosis by pressure measurements: a clinical outcome study.

AIM: The present study aimed to prospectively evaluate whether application of the concept of fractional flow reserve (FFR) guides the immediate decision to perform or to defer coronary angioplasty in unselected consecutive patients with one or more angiographically intermediate (50-70%) stenoses and non-conclusive or lacking non-invasive testing. METHODS: We studied 112 patients (81 males and 31 females, aged 31-81 years) including 71 multivessel disease patients (63%) and 30 patients (27%) with unstable symptoms. FFR was measured with the use of a pressure-wire after adenosine-induced hyperaemia and compared with quantitative coronary angiography in 171 stenoses. Coronary angioplasty was performed in the presence of an FFR < 0.75 and deferred if FFR was > or = 0.75. Cardiac events including death, myocardial infarction, recurrent angina or symptoms requiring repeated hospitalization and target vessel revascularization (TVR) were recorded during a median period of 34 months (interquartile range 9-54 months). RESULTS: Coronary angioplasty was deferred based on FFR results in 54 patients (group I). In the remaining 58 patients, angioplasty was performed in one or more stenoses that were significant by FFR and deferred in non-significant stenoses (group II). Overall, coronary angioplasty was performed in 71 vessels (41%) and deferred in 100 (59%). Cumulative cardiac events occurred in 12.9% of group I patients and in 24.1% of group II patients (chi-squared = 1.57, P = 0.20). TVR was required in 5% of the stenoses untreated based on FFR result in both groups and in 12.6% of stenoses that underwent coronary angioplasty (chi-squared = 3.25, P = 0.07; relative risk = 2.5, 95% confidence interval = 0.88-8.61). CONCLUSIONS: In patients with angiographically intermediate stenoses, functional evaluation by FFR to select lesions that do not need to be treated invasively is safe. Unnecessary angioplasty and stenting may be saved in more than one half of individual coronary stenoses. The risk of major cardiac events and TVR of functionally non-significant stenoses is lower than the risk associated with coronary angioplasty. Our observations further support the use of pressure wire for physiological assessment of coronary artery stenosis in the catheterization room.

A case of transient left ventricular apical ballooning. A condition simulating an acute myocardial infarction.

Transient left ventricular apical ballooning, sometimes associated with intraventricular pressure gradient, is a condition simulating an acute myocardial infarction and may occur in patients presenting with chest pain, electrocardiographic changes and minimal myocardial enzyme release typically without coronary angiographic stenosis. It was originally described in the Japanese population and is often associated with cerebrovascular accidents, surgical procedures and emotional and physical stress. We report the case of a 65-year-old woman presenting with chest pain typical of myocardial ischemia, dyspnea, electrocardiographic abnormalities and signs of hemodynamic instability, occurring after a severe emotional stress. Echocardiography and contrast ventriculography showed normokinesis confined to the basal segments of the left ventricle, with a markedly decreased ejection fraction. Scintigraphy was suggestive of a large perfusion defect. The electrocardiographic abnormalities and dyskinesis persisted for many hours. Coronary angiography, performed in the acute phase, was completely normal. Five months later, the functional and electrocardiographic abnormalities had totally disappeared.