In this article, we advance a hypothesis for the rupture of thin fibrous cap atheroma, namely that minute (10-μm-diameter) cellular-level microcalcifications in the cap, which heretofore have gone undetected because they lie below the visibility of current in vivo imaging techniques, cause local stress concentrations that lead to interfacial debonding. New theoretical solutions are presented for the local stress concentration around these minute spherical inclusions that predict a nearly 2-fold increase in interfacial stress that is relatively insensitive to the location of the hypothesized microinclusions in the cap. To experimentally confirm the existence of the hypothesized cellular-level microcalcifications, we examined autopsy specimens of coronary atheromatous lesions using in vitro imaging techniques whose resolution far exceeds conventional magnetic resonance imaging, intravascular ultrasound, and optical coherence tomography approaches. These high-resolution imaging modalities, which include confocal microscopy with calcium-specific staining and micro-computed tomography imaging, provide images of cellular-level calcifications within the cap proper. As anticipated, the minute inclusions in the cap are very rare compared with the numerous calcified macrophages observed in the necrotic core. Our mathematical model predicts that inclusions located in an area of high circumferential stress (>300 kPa) in the cap can intensify this stress to nearly 600 kPa when the cap thickness is <65 μm. The most likely candidates for the inclusions are either calcified macrophages or smooth muscle cells that have undergone apoptosis.

Background— We used intravascular ultrasound (IVUS) to evaluate recurrence after sirolimus-eluting stent (SES) implantation treatment of in-stent restenosis (ISR). Methods and Results— Forty-eight ISR lesions (41 patients with objective evidence of ischemia) were treated with SES. Recurrent ISR was identified in 11 lesions (all focal); repeat revascularization was performed in 10. These were compared with 16 patients (19 lesions) without recurrence as documented by angiography. Nine of 11 recurrent lesions had a minimum stent area (MSA) <5.0 mm ² versus 5 of 19 nonrecurrent lesions ( P =0.003); 7 of 11 recurrent lesions had an MSA <4.0 mm ² versus 4 of 19 nonrecurrent lesions ( P =0.02); and 4 of 11 recurrent lesions had an MSA <3.0 mm ² versus 1 of 19 nonrecurrent lesions ( P =0.03). A gap between SESs was identified in 3 of 11 recurrences versus 1 of 19 nonrecurrent lesions. Conclusions— Stent underexpansion is a significant cause of failure after SES implantation treatment of ISR.

Intravascular optical coherence tomography (OCT) has been proven a powerful diagnostic tool for cardiovascular diseases. However, the optical mechanism for the qualitative observations are still absent. We address the fundamental issues that underlie the tissue characterization of OCT images obtained from coronary arteries. For this, we investigate both the attenuation and the backscattering properties of different plaque components of postmortem human cadaver coronary arteries. The artery samples are examined both from lumen surface using a catheter and from transversely cut surface using an OCT microscope, where OCT images could be matched to histology exactly. Light backscattering coefficient $μb$ and attenuation coefficients $μt$ are determined for three basic plaque types based on a single-scattering physical model: calcification ($μb=4.9±1.5mm−1$, $μt=5.7±1.4mm−1$), fibers ($μb=18.4±6.4mm−1$, $μt=6.4±1.2mm−1$), and lipid pool ($μb=28.1±8.9mm−1$, $μt=13.7±4.5mm−1$). Our results not only explain the origins of many qualitative OCT features, but also show that combination of backscattering and attenuation coefficient measurements can be used for contrast enhancing and better tissue characterization.

Objectives: To examine the relation of arterial compliance to diastolic dysfunction in hypertensive patients with suspected diastolic heart failure (HF). Patients: 70 medically treated hypertensive patients with exertional dyspnoea (40 women, mean (SD) age 58 (8) years) and 15 normotensive controls. Main outcome measures: Mitral annular early diastolic velocity with tissue Doppler imaging and flow propagation velocity were used as linear measures of diastolic function. Arterial compliance was determined by the pulse pressure method. Results: According to conventional Doppler echocardiography of transmitral and pulmonary venous flow, diastolic function was classified as normal in 33 patients and abnormal in 37 patients. Of those with diastolic dysfunction, 28 had mild (impaired relaxation) and nine had advanced (pseudonormal filling) dysfunction. Arterial compliance was highest in controls (mean (SD) 1.32 (0.58) ml/mm Hg) and became progressively lower in patients with hypertension and normal function (1.04 (0.37) ml/mm Hg), impaired relaxation (0.89 (0.42) ml/mm Hg), and pseudonormal filling (0.80 (0.45) ml/mm Hg, p = 0.011). In patients with diastolic dysfunction, arterial compliance was inversely related to age (p = 0.02), blood pressure (p < 0.001), and estimated filling pressures (p < 0.01) and directly related to diastolic function (p < 0.01). After adjustment for age, sex, body size, blood pressure, and ventricular hypertrophy, arterial compliance was independently predictive of diastolic dysfunction. Conclusions: In hypertensive patients with exertional dyspnoea, progressively abnormal diastolic function is associated with reduced arterial compliance. Arterial compliance is an independent predictor of diastolic dysfunction in patients with hypertensive heart disease and should be considered a potential target for intervention in diastolic HF.