Hans Berglund

Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: An in vivo intravascular ultrasound study☆

OBJECTIVES This intravascular ultrasound study sought to examine to what extent native coronary artery stenosis is accompanied by vessel wall thickening or inadequate compensatory enlargement (relative vessel constriction), or both. BACKGROUND In human femoral arteries, inadequate compensatory enlargement is reported to be a paradoxic mechanism for the development of severe arterial lumen narrowing. However, it is unclear in human coronary arteries whether inadequate compensatory enlargement contributes to the development of critical arterial stenosis. METHODS Thirty-five primary coronary artery lesions from 30 patients (19 men, 11 women; mean [+/- SD] age 65 +/- 13 years) were imaged by intravascular ultrasound. The vessel cross-sectional area and lumen area were measured, and the wall area (vessel cross-sectional area minus lumen area) was calculated at the lesion site and at the proximal and distal reference sites. We defined compensatory enlargement to be present when the vessel cross-sectional area at the lesion site was larger than that at the proximal reference site, inadequate compensatory enlargement when the vessel cross-sectional area at the lesion site was smaller than that at the distal reference site and intermediate remodeling when the vessel cross-sectional area at the lesion site was intermediate between the two reference sites. RESULTS Compensatory enlargement was observed in 19 (54%) of 35 lesions, inadequate compensatory enlargement in 9 (26%) of 35 and intermediate remodeling in 7 (20%) of 35. In the inadequate compensatory enlargement group, reduction of the vessel cross-sectional area contributed to 39% of lumen reduction. CONCLUSIONS Compensatory enlargement commonly (54%) occurs at stenotic coronary lesions. However inadequate compensatory enlargement results in a substantial amount (39%) of the lumen area reduction in 26% of primary coronary artery lesions.

Clinical validation of intravascular ultrasound imaging for assessment of coronary stenosis severity: comparison with stress myocardial perfusion imaging.

OBJECTIVES To validate intravascular ultrasound (IVUS) measurements for differentiating functionally significant from nonsignificant coronary stenosis. BACKGROUND To date, there are no validated criteria for the definition of a flow-limiting coronary artery stenosis by IVUS. METHODS Preinterventional IVUS imaging (30-MHz imaging catheter) of 70 de novo coronary lesions was performed. The lesion lumen area and three IVUS-derived stenosis indixes comparing lesion lumen area with the lesion external elastic lamina (EEL) area, the mean reference lumen area and the mean reference EEL area were compared with the results of stress myocardial perfusion imaging. RESULTS The lesion lumen area and three IVUS-derived stenosis indexes showed sensitivities and specificities ranging between 80% and 90% using stress myocardial perfusion imaging as the gold standard. The lesion lumen area < or =4 mm2 is a simple and highly accurate criterion for significant coronary narrowing. CONCLUSIONS Quantitative IVUS indices can be reliably used for identifying significant epicardial coronary artery stenoses.

Transcutaneous Ultrasound Augments Lysis of Arterial Thrombi In Vivo

BACKGROUND External ultrasound has a synergistic effect on thrombus disruption with thrombolytic agents in vitro. We hypothesized that transcutaneous ultrasound could augment thrombolysis in vivo. METHOD AND RESULTS Thrombus formation was induced electrically in 48 pairs of iliofemoral arteries of 24 rabbits; arterial occlusions were documented angiographically. In 17 of 24 rabbits, 25000 units/kg streptokinase was then administered intravenously. The pairs of iliofemoral arteries were randomized to receive ultrasound treatment or no ultrasound treatment. Low-frequency (26 kHz) ultrasound (continuous wave, 18 W/cm2) was applied transcutaneously over the area of occlusion. In 7 of 24 rabbits, 14 thrombotically occluded iliofemoral arteries were exposed to ultrasound alone without streptokinase. The results were evaluated through the use of angiography (TIMI grade flow) and histopathology. After 30 +/- 10 minutes of activated sonication combined with intravenous streptokinase, 10 of 17 iliofemoral arteries (59%) treated with transcutaneous ultrasound were widely patent angiographically, with TIMI grade 3 flow. Histologically, the patent arteries had only minimal focal moral thrombus. The angiographic patency rate was significantly lower in the control groups: 1 of 17 arteries (6%) treated with streptokinase alone (P = .0012) and 1 of 14 arteries (7%) treated with ultrasound alone (P = .0036). CONCLUSIONS In vivo transcutaneous ultrasound significantly augments lysis of thrombi with streptokinase in rabbit iliofemoral arteries.

Dissolution of Thrombotic Arterial Occlusion by High Intensity, Low Frequency Ultrasound and Dodecafluoropentane Emulsion: An In Vitro and In Vivo Study ☆

OBJECTIVES We examined the effectiveness of the microbubbles of an echo contrast agent, dodecafluoropentane (DDFP) emulsion, to enhance low frequency ultrasound clot disruption in vitro and in vivo. BACKGROUND Ultrasound is reported to facilitate clot dissolution, and microbubbles could theoretically enhance ultrasound clot dissolution by augmenting cavitational effects. METHODS IN VITRO STUDIES The disruption rate of fresh human clots by ultrasound (24 kHz, 2.9 W/cm2) was examined in saline and DDFP emulsion. In vivo studies: Using a rabbit iliofemoral thrombotic occlusion model, recanalization rate and histopathologic findings were compared among groups treated with DDFP emulsion alone, transcutaneous ultrasound (20 kHz, 1.5 W/cm2) alone and with DDFP emulsion and ultrasound combined. RESULTS The ultrasound clot disruption rate was significantly (p < 0.01) increased, from 72 +/- 18% (mean +/- SD) in saline to 98 +/- 4% in DDFP emulsion in 3 min in vitro. No vessel was recanalized by DDFP emulsion alone (0%), and only a single artery was patent after ultrasound treatment alone (9%). In contrast, 82% of iliofemoral arteries were angiographically recanalized after ultrasound treatment with DDFP emulsion. Histologically, the patent arteries had only minimal focal mural thrombus, with no evidence of vessel wall damage. However, substantial damage was observed in rabbit dermis and subcutaneous tissue. CONCLUSIONS 1) DDFP emulsion, an echo contrast agent, significantly enhances the clot-disrupting effect of low frequency ultrasound in vitro and in an in vivo rabbit iliofemoral occlusion model. 2) This simple combination therapy has potential for clinical application in patients with thrombotic arterial occlusions.

Heterogeneous aortic response to acute β-adrenergic blockade in Marfan syndrome ☆ ☆☆ ★ ★★

Abstract Although prophylactic treatment with β-blockers is used to retard aortic root dilatation in Marfan syndrome, it is not effective in all patients. To assess the effects of β-adrenergic blockade on the aortas elastic properties, aortic stiffness index and distensibility were calculated in 13 patients with Marfan syndrome and 10 control subjects before and after β-adrenergic blockade. At baseline, patients with Marfan syndrome had a significantly increased stiffness index and decreased distensibility. After β-adrenergic blockade, 8 patients with Marfan syndrome developed stiffness indexes and distensibility values that were closer to normal, whereas these variables deteriorated in 5 patients. Thus the benefit of β-adrenergic blockade in Marfan syndrome may be the reduction in pulse pressure and myocardial contractility and also promotion of the elastic properties of the aorta. Moreover, the differential responses of aortic mechanics (normalizing or worsening) to β-adrenergic blockade may possibly have implications for the prognosis in these patients. (Am Heart J 1997;133:60-3.)

Highly Localized Arterial Remodeling in Patients With Coronary Atherosclerosis An Intravascular Ultrasound Study

BACKGROUND Preservation of luminal area and symmetry in the presence of irregular plaques necessitates local expansion of the artery wall. METHODS AND RESULTS Cross-sectional dimensions of coronary arteries in 65 patients were measured with the use of intravascular ultrasound. A total of 104 arterial segments were studied, of which 88 had atherosclerosis; 16 served as nonatherosclerotic control segments. Three features of atherosclerotic arterial segments were classified: (1) plaque formation, (2) lumen shape, and (3) shape of arterial external elastic lamina. With our intravascular ultrasound-based three-level classification system, we identified three patterns that accounted for 89% of all atherosclerotic arterial segments: (1) concentric plaque with a circular lumen and a circular external elastic lamina (n= 17), (2) eccentric plaque with a circular lumen and an oval external elastic lamina (n=35), and (3) eccentric plaque with an oval lumen and a circular external elastic lamina (n=26). A circular lumen was preserved in 66% of all atherosclerotic arterial segments. Arterial segments with a circular lumen in the presence of an eccentric plaque had a significantly larger lumen area than the other two main groups (P<.05). CONCLUSIONS With our intravascular ultrasound-based classification, we provided information regarding the local remodeling response in the coronary artery wall. In a majority of cases, a circular lumen is maintained. Failure of this highly localized response to be operative may contribute to the development of stenotic lesions at a specific site in the artery.

Absence of Focal Compensatory Enlargement or Constriction in Diseased Human Coronary Saphenous Vein Bypass Grafts An Intravascular Ultrasound Study

BACKGROUND No in vivo data are available on the occurrence of compensatory enlargement or vessel constriction in diseased human coronary saphenous vein bypass grafts (SVBGs). The aim of this intravascular ultrasound (IVUS) study was to examine to what extent lumen reduction is accompanied by (1) vessel wall thickening and (2) arterial wall constriction in SVBGs. METHODS AND RESULTS We used IVUS to examine 43 SVBGs from 42 patients (32 men, 10 women; mean age, 72 +/- 5 years) 8 to 23 (11 +/- 4) years after SVBG. IVUS images were obtained with a 3.5F monorail ultrasound catheter with a 30-MHz frequency and were analyzed at the lesion site, the reference site, and an intermediate site. The lumen area was significantly (P < .01) decreased; the vessel wall area (SVBG cross-sectional area minus lumen area) and the plaque area (area within the external elastic lamina minus lumen area) were significantly (P < .01) increased from the reference site through the lesion site. However, SVBG cross-sectional area was the same at these three sites (24.0 +/- 8.1 versus 24.4 +/- 8.6 versus 24.5 +/- 8.6 mm2, P = NS), and the external elastic lamina area was also quite constant in each vessel (17.8 +/- 6.0 versus 17.7 +/- 6.4 versus 17.6 +/- 6.2 mm2, P = NS). CONCLUSIONS These in vivo IVUS data from human coronary SVBGs demonstrate that (1) no focal compensatory enlargement or vessel constriction occurred in stenotic segments compared with the reference segments and that (2) the absence of focal compensatory enlargement appears to be a potentially important factor in the progression of stenoses in coronary SVBGs.

Effect of external ultrasound frequency on thrombus disruption in vitro

Objectives: This in vitro study assesses the effect of different external ultrasound frequencies on the disruption of human thrombi. Background: Ultrasound energy has been shown to disrupt human thrombi in vitro. However, there have been no previous studies to assess the effect of a range of different ultrasound frequencies on the rate and extent of thrombus disruption. Methods: In vitro, we exposed 56, 1- to 3-hour-old human blood thrombi to continuous wave ultra-sound (2.9 W/cm2) for 3 minutes. Seven different frequencies, ranging from 243 kHz to 25 kHz, were used. Results: There was a gradual increase in the total reduction of thrombus weight as well as the percent thrombus disruption with the use of lower ultrasound frequencies, reaching 99% at 25 kHz (p < 0.001) and 86% (p < 0.001) at 39 kHz, compared with 25% at 243 kHz. The average particle size of the disrupted thrombi was 3.26 μm (range 2.8–3.8). Conclusions: Our in vitro data with external ultrasound show that for a given power intensity of ultrasound, the extent and magnitude of thrombus disruption is progressively increased as frequencies decrease from 243 to 25 kHz. This might be related to the fact that larger acoustic bubbles are induced by lower frequency ultrasound, which gives rise to greater mechanical energy for thrombus disruption during bubble vibration and their collapse.

Cooling System Permits Effective Transcutaneous Ultrasound Clot Lysis In Vivo Without Skin Damage

Previous in vivo studies have shown that transcutaneous ultrasound enhances clot dissolution in the presence of either streptokinase or microbubbles. However, ultrasound-induced skin damage has been a major drawback. The objective was to evaluate the effect of a cooling system to prevent the skin damage that has heretofore been associated with transcutaneous low-frequency, high-intensity ultrasound clot dissolution. After thrombi were induced in both iliofemoral arteries in 15 rabbits, streptokinase (25,000 U/kg) was given intravenously and dodecafluoropentane was injected slowly (2 mL/15 min) through an infusion catheter into the abdominal aorta. One iliofemoral artery was randomized to receive ultrasound treatment, and the contralateral artery was treated as a control (receiving streptokinase and dodecafluoropentane alone). In six rabbits (group 1), the skin below the ultrasound transducer was protected by the use of a balloon cooling system, and in the other nine rabbits (group 2), ultrasound was used without a cooling system. Seven of nine (78%) arteries treated without the cooling system, and six of six (100%) arteries treated with the cooling system were angiographically recanalized after ultrasound + streptokinase + dodecafluoropentane treatment. Thermal damage was present in the skin and soft tissues of all nine rabbits treated without a cooling system. However, the skin and soft tissues were grossly and histologically normal in the six rabbits in which the transcutaneous ultrasound was used with the cooling system. Low-frequency, high-intensity ultrasound energy can be delivered transcutaneously for clot dissolution without concomitant tissue damage when coupled with the use of a cooling system to prevent thermal injury.

Usefulness of transesophageal echocardiography for positioning the intraaortic balloon pump in the operating room

Abstract In conclusion, TEE is useful for precise positioning of the IABP catheter in the operating room without the use of x-ray fluoroscopy.