Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles.

OBJECTIVE: The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis. METHODS: This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed. RESULTS: The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group. CONCLUSION: Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size.

Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles

OBJECTIVE: The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis. METHODS: This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed. RESULTS: The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group. CONCLUSION: Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size.

Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary Lumen in Segments with or without Atherosclerotic Plaques.

BACKGROUND: The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has been poorly described and is mainly restricted to reports analyzing segments with documented atherosclerotic plaques. OBJECTIVES: We compared 64-slice multidetector computed tomography (MDCT) with gray scale intravascular ultrasound (IVUS) for the evaluation of coronary lumen dimensions in the context of a comprehensive analysis, including segments with absent or mild disease. METHODS: The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was obtained for at least one coronary, regardless of the presence of luminal stenosis at angiography. A total of 21 patients were included, with 70 imaged vessels (total length 114.6 ± 38.3 mm per patient). A coronary plaque was diagnosed in segments with plaque burden > 40%. RESULTS: At patient, vessel, and segment levels, average lumen area, minimal lumen area, and minimal lumen diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01). However, 64-slice MDCT tended to underestimate the lumen size with a relatively wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS lumen measurements was not substantially affected by the presence or absence of an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for the detection of IVUS parameters associated with flow-limiting lesions. CONCLUSIONS: In a comprehensive, multi-territory, and whole-artery analysis, the assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed a good overall diagnostic ability, regardless of the presence or absence of underlying atherosclerotic plaques.

Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary Lumen in Segments with or without Atherosclerotic Plaques / Comparação da TCMD e da USIV em escala de cinza na Análise Quantitativa da Luz Coronária em Segmentos com ou sem Placas Ateroscleróticas

Background: The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has been poorly described and is mainly restricted to reports analyzing segments with documented atherosclerotic plaques. Objectives: We compared 64-slice multidetector computed tomography (MDCT) with gray scale intravascular ultrasound (IVUS) for the evaluation of coronary lumen dimensions in the context of a comprehensive analysis, including segments with absent or mild disease. Methods: The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was obtained for at least one coronary, regardless of the presence of luminal stenosis at angiography. A total of 21 patients were included, with 70 imaged vessels (total length 114.6 ± 38.3 mm per patient). A coronary plaque was diagnosed in segments with plaque burden > 40%. Results: At patient, vessel, and segment levels, average lumen area, minimal lumen area, and minimal lumen diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01). However, 64-slice MDCT tended to underestimate the lumen size with a relatively wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS lumen measurements was not substantially affected by the presence or absence of an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for the detection of IVUS parameters associated with flow-limiting lesions. Conclusions: In a comprehensive, multi-territory, and whole-artery analysis, the assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed a good overall diagnostic ability, regardless of the presence or absence of underlying atherosclerotic plaques. .

Fundamento: A comparação do rigor diagnóstico da TCMD e da USIV foi pouco descrita, estando restrita principalmente a estudos que avaliaram segmentos com placas ateroscleróticas já documentadas. Objetivos: Este estudo objetiva avaliar o desempenho diagnóstico da tomografia computadorizada com 64 colunas de detectores (tomografia computadorizada multidetector- TCMD) e da ultrassonografia intravascular (USIV) em escala de cinza na verificação das dimensões da luz coronária, em um contexto mais amplo, incluindo também segmentos coronários sadios e com patologia leve. Métodos: A TCMD foi realizada em todos os pacientes antes da realização da USIV, com um intervalo < 72 horas entre os dois exames. Imagens de USIV foram obtidas de pelo menos uma coronária, independente da presença de estenose luminal durante a angiografia. Um total de 21 pacientes foram incluídos, com imagens de 70 vasos (comprimento total 114,6 ± 38.3 mm por paciente). Placas coronárias foram diagnosticada em segmentos com carga de placas > 40%. Resultados: Uma alta correlação entre as medidas de TCMD e USIV para área luminar média, área luminar mínima e diâmetro luminar mínimo foi encontrada no nível de paciente, vaso e segmento (p-valor < 0,01 para todas as correlações). A TCMD, no entanto, tendeu a subestimar o tamanho luminar com uma dispersão de diferenças relativamente ampla. A comparação entre as medidas da luz por TCMD e USIV não foi substancialmente afetada pela presença ou ausência de placa subjacente. Além disso, a TCMD mostrou boa precisão geral na detecção de parâmetros associados a lesões limitantes de fluxo. Conclusão: Em uma análise compreensiva e multi-focal da luz coronária, demonstramos bom desempenho diagnóstico da TCMD, quando comparada a USIV, independente da presença de placas ateroscleróticas adjacentes. .

Dipyridamole stress and rest transmural myocardial perfusion ratio evaluation by 64 detector-row computed tomography.

BACKGROUND: Myocardial stress CT perfusion (CTP) can detect myocardial ischemia. OBJECTIVE: We evaluated the transmural perfusion ratio (TPR) of dipyridamole stress CTP to detect significant coronary stenosis (>70%) defined by quantitative invasive coronary angiography (ICA). METHODS: Twenty-six patients (61.6 ± 8.0 years old; 14 males), without prior myocardial infarction, with positive single-photon emission computed tomography (SPECT; <2 months) and clinical indication for ICA, underwent a customized multidetector-row CT (MDCT) protocol with rest/stress myocardial perfusion evaluation and coronary CT angiography. TPR was defined as mean subendocardial divided by mean subepicardial attenuation and quantified on rest and stress MDCT images. Abnormal TPR was defined as 2 SDs below the mean rest TPR. RESULTS: All 26 patients completed the CT protocol with no adverse events. Rest TPR was measured in all patients with a mean of 1.06 ± 0.11, and abnormal TPR was considered <0.85. For 6 patients with normal coronary arteries by ICA, the mean TPR of territories with a previous positive perfusion defect in SPECT was 1.02 ± 0.18 (95% CI, 0.86-1.18; n = 6), and mean TPR of territories without perfusion defect in SPECT was 1.03 ± 0.09 (95% CI, -0.95 to 1.11; n = 12; P = 0.83). Mean stress TPR in territories with positive SPECT and significant coronary artery disease by quantitative ICA was 0.71 ± 0.13 (95% CI, -0.64 to 0.77) and in the remote myocardial was 1.01 ± 0.09 (95% CI, -0.96 to 1.06; P < 0001). In these territories, a significant Pearson's correlation was observed (r = -0.74, P < 0.001). CONCLUSION: TPR has a good correlation with SPECT and ICA to detect significant coronary stenosis.

Late gadolinium enhancement magnetic resonance imaging in the diagnosis and prognosis of endomyocardial fibrosis patients.

BACKGROUND: Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiography is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of EMF has not been investigated. METHODS AND RESULTS: Thirty-six patients (29 women; age, 54±12 years) with EMF diagnosis after clinical evaluation and comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes, ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole (mL/m(2)). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most prominent. There was a relation between increased FT/body surface area and worse New York Heart Association functional class and with increased probability of surgery (P<0.05). The histopathologic examination of resected FT showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area >19 mL/m(2) had an increased mortality rate, with a relative risk of 10.8. CONCLUSIONS: Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition.

Dipyridamole stress and rest myocardial perfusion by 64-detector row computed tomography in patients with suspected coronary artery disease.

Recently, stress myocardial computed tomographic perfusion (CTP) was shown to detect myocardial ischemia. Our main objective was to evaluate the feasibility of dipyridamole stress CTP and compare it to single-photon emission computed tomography (SPECT) to detect significant coronary stenosis using invasive conventional coronary angiography (CCA; stenosis >70%) as the reference method. Thirty-six patients (62 +/- 8 years old, 20 men) with previous positive results with SPECT (<2 months) as the primary inclusion criterion and suspected coronary artery disease underwent a customized multidetector-row CT protocol with myocardial perfusion evaluation at rest and during stress and coronary CT angiography (CTA). Multidetector-row computed tomography was performed in a 64-slice scanner with dipyridamole stress perfusion acquisition before a second perfusion/CT angiographic acquisition at rest. Independent blinded observers performed analysis of images from CTP, CTA, and CCA. All 36 patients completed the CT protocol with no adverse events (mean radiation dose 14.7 +/- 3.0 mSv) and with interpretable scans. CTP results were positive in 27 of 36 patients (75%). From the 9 (25%) disagreements, 6 patients had normal coronary arteries and 2 had no significant stenosis (8 false-positive results with SPECT, 22%). The remaining patient had an occluded artery with collateral flow confirmed by conventional coronary angiogram. Good agreement was demonstrated between CTP and SPECT on a per-patient analysis (kappa 0.53). In 26 patients using CCA as reference, sensitivity, specificity, and positive and negative predictive values were 88.0%, 79.3%, 66.7%, and 93.3% for CTP and 68.8, 76.1%, 66.7%, and 77.8%, for SPECT, respectively (p = NS). In conclusion, dipyridamole CT myocardial perfusion at rest and during stress is feasible and results are similar to single-photon emission CT scintigraphy. The anatomical-perfusion information provided by this combined CT protocol may allow identification of false-positive results by SPECT.

An unusual case of angina pectoris: a patient with isolated non-compaction of the left ventricular myocardium.

A 29-year-old white woman with typical angina pectoris presented diastolic dysfunction and was suggestive of isolated non-compaction of the ventricular myocardium (INCM) by echocardiography. Cardiac catheterization disclosed normal coronary arteries. Cardiovascular magnetic resonance (CMR) depicted prominent left ventricular INCM areas with non-compaction/compaction ratio of 3.7, and dipyridamole CMR demonstrated global perfusion defect at stress and normal perfusion at rest. Adenosine-induced vasodilation showed subnormal coronary velocity flow reserve in the right, left circumflex, and left anterior descending coronary arteries. The evidence of our case indicates that patients with INCM may present angina pectoris and, probably, relative chronic myocardial ischaemia related to an impaired microvascular function is responsible for this symptom as demonstrated invasively here. It is a possible mechanism for progressive myocardial dysfunction seen in these patients.

Spontaneous aortic dissection limited to sinus of Valsalva and involving the left main coronary artery.

Aortic dissection limited to one sinus of Valsalva has been described exclusively as an iatrogenic complication during catheterization interventions. This life-threatening subtype had a very small area of dissection, when coronary ostia are frequently involved. We report a 43-year-old man with dissection limited to left sinus of Valsalva, involving the left main coronary artery and causing non-ST-myocardial infarction, including severe reversible ST-depression, maximum of 9 mm in V5 lead. Dissection was suggested by cineangiography, transesophageal echocardiogram, and contrast-enhanced multidetector computed tomography. Surgical treatment was successful. There were not any associated diseases in the sinuses of Valsalsa, aortic valve or coronary arteries. Unlike previous reported cases of aortic dissection with such limited localization, the present case was spontaneous, and not iatrogenic.