Intravenous Dipyridamole Research Articles

CORONARY MICROVASCULAR DYSFUNCTION IN PATIENTS AFTER URGENT PERCUTANEOUS CORONARY INTERVENTION DUE TO ACUTE CORONARY SYNDROME

Background. Possible cause of residual myocardial ischemia after urgent PCI during ACS is coronary microvascular dysfunction. Aim: To study the frequency of coronary microvascular dysfunction in patients who underwent urgent PCI due to ACS. Materials and methods. The study included 38 participants with ACS. These patients underwent urgent PCI. After 28 days patients underwent echocardiography with intravenous dipyridamole. Coronary microvascular dysfunction was determined by an CFR less than 2. Quality of life was measured by the severity of angina using the SF-36 and SAQ questionnaires, respectively. To compare the results of the study, a cohort of 20 patients who underwent elective PCI without coronary microvascular dysfunction (CFR≥2) were selected. Results.About 2/3 of patients had complaints of shortness of breath, as the equivalent of angina pectoris, during routine physical exertion. In 83.3% patients presence of coronary microvascular dysfunction, was proven. Quality of life due to the SAQ and SF-36 questionnaires were significantly lower among patients, who underwent urgent PCI. Conclusion.The results of the work showed that 83.3% of patients after urgent PCI for ACS were diagnosed with coronary microvascular dysfunction.

Prevalence of Coronary Microvascular Dysfunction in Patients after Coronary Artery Bypass Grafting

The aim. To analyze the prevalence of coronary microvascular dysfunction (CMD) in patients with coronary artery disease after coronary artery bypass grafting (CABG).
 Materials and methods. The study was conducted in compliance with the provisions of the Declaration of Helsinki and was approved by the local ethics committee during 2018-2021. Due to recurrent complaints of discomfort/pain behind the sternum or shortness of breath during physical exertion in patients after CABG (average time of occurrence 18 ± 6 months after surgery), as well as positive or doubtful result of the stress testing, 31 patients were re-hospitalized for further examination. To diagnose CMD, echocardiography was performed with intravenous dipyridamole in order to determine the coronary flow reserve. The patency of the grafts was confirmed and newly formed hemodynamically significant coronary artery lesions were excluded during invasive coronary angiography.
 Results. The mean age was 61.2 ± 2.3 years, the majority of the patients were male (20 [64.5%]). The most common comorbid pathologies in the patients were: hypertension in 29 patients (93.5%), impaired glucose metabolism (diabetes/prediabetes) in 17 (54.8%) subjects, 13 (41.9%) patients had a history of myocardial infarction. Left ventricular ejection fraction according to echocardiography was reduced (less than 55%) in 5 (16.1%) of 31 patients, in others it was preserved. After CABG, there was a trend towards the coronary flow reserve increase, but no significant difference was found (1.89 ± 0.08 vs. 2.11 ± 0.13; p > 0.05). The presence of CMD before and after CABG did not change significantly (13 [41.9%] vs. 12 [38.7%]; p > 0.05).
 Conclusion. According to the results of the study, CMD is a common pathology in patients with obstructive coronary artery disease and is found in about 40% of patients with repeated myocardial ischemia after CABG. CABG did not affect the frequency of detection of CMD in patients with coronary artery disease before and after the operation.

Dynamics of Right Ventricle Pressure During Stress Echocardiography in Patients with Heart Failure with Preserved Ejection Fraction

Shortness of breath during physical exertion is a non-specific symptom that can hide such potentially dangerous diseases as structural or functional bronchopulmonary, coronary heart disease, structural cardiac disease, but the frequent cause is left ventricle diastolic dysfunction due to its significant hypertrophy. Pathogenetic mechanisms leading to this symptom require detailed study for the possibility of a comprehensive approach in the treatment of such patients with the aim of maximally improving their prognosis and quality of life. Objective — evaluate changes in right ventricle systolic pressure during stress echocardiography in patients with LV myocardial hypertrophy and clinical manifestations of heart failure, search for other mechanisms leading to clinical symptoms. Materials and methods. The study included 49 patients with shortness of breath during physical exertion, who underwent further diagnostic examination after exclusion of coronary stenotic lesions by invasive coronary and ventricular angiography. Patients were excluded from bronchopulmonary pathology using spirometry and chest radiography, structural heart pathology using echocardiography, microvascular angina using echocardiography with intravenous dipyridamole infusion, and the change in systolic pressure in the right ventricle was investigated using echocardiography during a physical exercise test. Results and discussion. There were no cases of infiltrative lung changes, signs of emphysema, or other manifestations of significant pathology according to X-ray data. Spirometry also showed the absence of significant functional abnormalities. Echocardiography revealed significant hypertrophy of LV myocar­dium (thickness of IVS — on average (14.1 ± 0.5) mm, posterior wall thickness — on average (13.5 ± 0.3) mm) with the presence of LV diastolic dysfunction and echocardiographic signs of increased end-diastolic pressure in the LV, which was confirmed invasively during coronary and ventricular angiography. In 9 (18.4 %) cases, heart wall thickening was due to hypertrophic cardiomyopathy according to cardiac MRI, these patients had LV outflow tract obstruction and mild pulmonary hypertension at rest. Conducting strain imaging showed the presence of signs of myocardial ischemia (segmental contractility disorder) with varying degrees of severity (from 1 to 5 segments), which spread to the IVS, the apex of the heart and, less often, to the anterior wall of the LV. All patients experienced an increase in pulmonary artery systolic pressure during exercise, on average, from (37.4 ± 2.1) to (47.1 ± 1.6) mm Hg. Conclusions. The pathogenic mechanism underlying shortness of breath in patients with LV myocardial hypertrophy involves transient pulmonary hypertension occurring during exercise due to left ventricular diastolic dysfunction. Another contributing factor is the development of myocardial ischemia during physical exertion, which, in the absence of coronary stenosis and microvascular angina, is attributed to inadequate supply of coronary blood flow volume velocity relative to the significant left ventricular hypertrophy.

Arterial Spin Labeling Imaging Assessment of Cerebrovascular Reactivity in Hypertensive Small Vessel Disease.

Objective: Cerebrovascular reactivity (CVR) represents the phenomenon where cerebral vessels dilate or constrict in response to vasoactive stimuli. CVR impairment may contribute to brain injury due to cerebral small vessel disease (SVD). We aimed to determine the CVR in hypertensive intracerebral hemorrhage (ICH) and to identify its vascular dysfunction.Methods: A total of 21 patients with spontaneous hypertensive ICH (strictly deep or mixed deep and lobar hemorrhages, mean age 62.5 ± 11.3 years) and 10 control subjects (mean age 66.1 ± 6.0 years) were enrolled for CVR measurement at least 3 months after the symptomatic ICH event. Each participant underwent a brain MRI study, and CVR was calculated as the cerebral blood flow (CBF) reduction using arterial spin labeling (ASL) between baseline and 10 min after an intravenous dipyridamole injection (0.57 mg/kg). Traditional MRI markers for SVD were also evaluated, including cerebral microbleed, white matter hyperintensity, lacune, and MRI-visible enlarged perivascular space, which were used to determine the total small vessel disease score.Results: Compared to control subjects, hypertensive ICH patients showed reduced CVR in the basal ganglia (CBF reduction 22.4 ± 22.7% vs. 41.7 ± 18.3, p = 0.026), the frontal lobe (15.1 ± 11.9 vs. 26.6 ± 9.9, p = 0.013), and the temporal lobe (14.7 ± 11.1 vs. 26.2 ± 10.0, p = 0.010). These differences remained significant in multivariable models after adjusting for age and sex. Within ICH groups, the CBF reduction in the basal ganglia was significantly correlated with the total small vessel disease score (R = 0.58, p = 0.006), but not with individual MRI markers.Conclusion: Patients with advanced hypertensive SVD demonstrated impaired vasoconstriction after dipyridamole challenge in the basal ganglia and the frontal and temporal lobes. Our findings provide safe approaches for whole-brain CVR mapping in SVD and identify a potential physiological basis for vascular dysfunction in hypertensive SVD.

Reverse redistribution-like change on dipyridamole-stress 99mTc-tetrofosmin imaging in a patient with angiographically mild coronary artery stenosis

A 50-year-old man with a 1-month history of chest pain presented to our hospital. Transthoracic echocardiography showed normal left ventricular wall motion. Coronary computed tomography angiography revealed a mild stenosis with low-density non-calcified plaque in the proximal left anterior descending coronary artery (LAD) (Figure 1A, yellow arrows); therefore, the patient underwent a 1-day protocol of dipyridamole stress and rest 99mTc-tetrofosmin myocardial perfusion imaging (MPI). Baseline electrocardiography was normal; however, he developed angina 8 minutes after the start of .56 mg·kg−1 (.14 mg·kg−1·min−1 for 4 minutes) of intravenous dipyridamole infusion and his electrocardiogram showed ST-segment elevation in the precordial leads (Figure 2). After intravenous aminophylline with sublingual nitroglycerin was given, the ST-segment elevation was gradually resolved. Stress MPI showed no perfusion defect (Figure 1B) with abnormal wall motion in the anterior and septal walls on gated MPI (Supplementary Material). He had recurrent angina after the stress MPI. Rest MPI at 2 hours after the stress test showed reverse redistribution-like reduced uptake in the LAD territory (Figure 1B) with normal left ventricular wall motion on gated MPI (Supplementary Material). As with the coronary computed tomography, invasive coronary angiography via the right radial artery demonstrated the mild stenosis in the proximal LAD (Figure 3, yellow arrow). Intravascular ultrasound and optical coherence tomography images showed coronary plaque with neovascularization (Figure 3, red arrows) and small thrombi (Figure 3, white arrows) at the minimum lumen area site, indicating the increased vulnerability of the coronary plaque.1 Percutaneous coronary intervention (PCI) with a drug-eluting stent (4.0 × 33 mm) was successfully performed (Figure 3, red arrows). On the day following the PCI, he underwent cardiopulmonary exercise testing and did not present with chest pain at peak exercise (VO2 at peak was 22.5 mL·kg−1·min−1 [6.4 METs]). Open in a separate window Figure 1 (A) Coronary computed tomography angiography revealed a mild stenosis (yellow arrows) with low-density non-calcified plaque in the proximal left anterior descending coronary artery (LAD). (B) Dipyridamole stress and rest 99mTc-tetrofosmin myocardial perfusion imaging (MPI). Stress MPI (300 MBq of 99mTc-tetrofosmin) showed no perfusion defect, whereas rest MPI (900 MBq of 99mTc-tetrofosmin) 2 hours after the stress test showed reduced uptake (reverse redistribution) in the LAD territory

Análise Comparativa do Padrão de Fluxo de Artérias Coronárias das Hipertrofias Miocárdicas Secundárias e por Mutação Sarcomérica

Background: Coronary flow with a diastolic predominance increases two to five times in hyperemia, mediated by vasodilation (coronary flow reserve, CFR) and, in hypertrophy, relative ischemia may occur. In secondary hypertrophy (LVH), the flow, normal at rest, becomes ischemic due to increased demand. In hypertrophic cardiomyopathy (HCM) with perivascular fibrosis, collateral vessels appear to increase the irrigation of hypertrophied segments. Objective: To determine the coronary flow pattern in patients with secondary hypertrophy and hypertrophic cardiomyopathy,evaluating the coronary flow reserve. Methods: Coronary flow was evaluated in 34 patients with secondary hypertrophy, 24 with hypertrophic cardiomyopathy and in 16 controls. The anterior descending artery was detected with transthoracic Doppler with adequate equipment calibration. In the hypertrophic cardiomyopathy group, the flow of collaterals from the hypertrophic region was evaluated. In the control and secondary hypertrophy groups and in six patients in the hypertrophic cardiomyopathy group, the intravenous dipyridamole (0.84 mg) coronary flow reserve was calculated. The data were compared by variance with a significance of 5%. Results: In secondary hypertrophy there was an increase in mass index and blood pressure, and in hypertrophic cardiomyopathy an increase in relative thickness predominated. Ejection fraction and diastolic dysfunction were higher in the hypertrophic cardiomyopathy group. The coronary flow reserve was lower in the hypertrophic cardiomyopathy group, and flow of collaterals was also detected, with a reduction in the coronary flow reserve. Conclusion: the analysis of coronary circulation with transthoracic Doppler is possible in normal and hypertrophic individuals. Patients with secondary hypertrophy and hypertrophic cardiomyopathy have a decrease in the coronary flow reserve, and patients with hypertrophic cardiomyopathy show a hyper flow of dilated collateral vessels observed in the hypertrophic region, with a decrease in the coronary flow reserve.

Abstract MP42: Arterial Spin Labeling Imaging Assessment of Cerebrovascular Reactivity in Hypertensive Small Vessel Disease

Objective: Cerebrovascular reactivity (CVR) represents the phenomenon that cerebral vessels dilate or constrict in response to vasoactive stimuli, and CVR impairment may contribute to the brain injury caused by cerebral small vessel disease (SVD). We aim to determine the CVR in hypertensive intracerebral hemorrhage (ICH) and to identify its vascular dysfunction. Methods: 21 patients with spontaneous hypertensive ICH (strictly deep or mixed deep and lobar hemorrhages, mean age 62.5 ± 11.3 years) and 10 control subjects (mean age 66.1 ± 6.0) were enrolled for CVR measurement. Each participant received a brain MRI study, and CVR was calculated as cerebral blood flow (CBF) change using arterial spin labeling (ASL) sequence at baseline and 10 minutes after intravenous dipyridamole injection (0.57mg/Kg). Traditional MRI markers for SVD including cerebral microbleed, white matter hyperintensity, lacune and MRI-visible enlarged perivascular space were also evaluated to determine the total small vessel disease score. Results: Hypertensive ICH patients showed reduced CVR in the basal ganglia (CBF change 22.4 ± 22.7% vs. 41.7 ± 18.3, p=0.026), the frontal (15.1 ± 11.9 vs. 26.6 ± 9.9, p=0.013) and the temporal lobes (14.7 ± 11.1 vs. 26.2 ± 10.0, p=0.010) compared to control subjects (Figure). These differences remained significant in multivariable models after adjusting for age, sex, hypertension, diabetes, and hyperlipidemia. Within ICH groups, the CBF change in basal ganglia was significantly correlated with total small vessel disease score (R=-0.58, p=0.006), but not with individual MRI markers. Conclusion: Patients with advanced HTN-SVD demonstrated impaired vasoconstriction after dipyridamole challenge in basal ganglia, frontal and temporal lobes. Our findings provide safe approaches for whole brain CVR mapping in small vessel disease, and identify the potential physiological basis of vascular dysfunction in HTN-SVD.

Sudden sensorineural hearing loss during pregnancy: etiology, treatment, and outcome.

ObjectiveTo analyze the etiologies, treatments, and outcomes of sensorineural hearing loss (SSNHL) during pregnancy.Study designRetrospective chart review of 25 pregnant patients treated for SSNHL between January 2012 and September 2019. Forty-nine age matched non-pregnant women with severe and profound hearing loss diagnosed with SSNHL during the same period served as controls. Data were recorded on age, symptoms, onset of hearing loss, audiometric results, treatments, and outcomes.ResultsThe mean age was 29.6 years (range 23–38 years). Intratympanic steroids (ITS) were administered in 15 (60.0%) pregnant women with SSNHL. Three women were treated with postauricular steroids only, while another woman was treated with intravenous ginkgo leaf extract and dipyridamole. The remaining six women received no medications. More than half (8/15, 53.3%) of pregnant women with SSNHL receiving ITS experienced hearing improvement. Pregnant women with profound hearing loss who received no medication had no hearing improvement. Most pregnant women with SSNHL (12/15, 80.0%) had higher fibrinogen levels than controls (mean values 3.77±0.71 g/L and 2.54±0.48 g/L, respectively).ConclusionFibrinogen could be a risk factor for SSNHL during pregnancy. ITS may benefit pregnant women with severe and profound SSNHL.

Detection of silent cerebral microcirculatory abnormalities in patients with manifest ischemic coronary disease: a perfusion brain MRI study combined with dipyridamole stress

Objectives Intravenous dipyridamole (DP) can induce transient perfusion abnormalities in the heart but also the brain indicated by brain SPECT. L-arginine can regulate the vascular tone via nitric oxide (NO). Therefore, we examined cerebral blood volume (CBV) by perfusion MRI and L-arginine level before and after DP stress in patients, who developed transient neurological signs, and compared these to unaffected patients. Design A total of nine patients with ischemic coronary disease after myocardial perfusion scintigraphy were selected for this prospective pilot study. Four had DP-induced transient mild neurologic signs during myocardial perfusion scintigraphy, while five had no neurological signs. By using perfusion MRI in both groups in a second stage, we examined CBV in identical areas of the two hemispheres before and during DP stress. Besides, pre-and post-stress L-arginine serum levels were also analyzed by high-performance liquid chromatography. Trial registration: NCT03688815. Results CBV in the sensory-motor area at baseline was significantly higher in patients with DP-induced transient neurological signs compared to patients without signs (p = 0.028). Intravenous DP normalized the higher perfusion by decreasing CBV, and also increased serum L-arginine level (p = 0.001). Conclusions Intravenous DP changed the CBV accompanied by a systemic elevation of L-arginine: this indicates a direct vasorelaxing effect on brain vessels, and an indirect vasodilator effect through L-arginine release presumably via NO. In areas with decreased CBV before DP, such double effects caused transient neurological symptoms presumably due to steal phenomenon. Therefore, intravenous DP may have a potential to identify patients with high risk for cerebral ischemia.

Does intravenous dipyridamole administration cause acute renal impairment?

Does intravenous dipyridamole administration cause acute renal impairment?

Myocardial Perfusion Imaging in Takayasu Arteritis

Myocardial perfusion defects using scintigraphy have been frequently observed in patients with Takayasu arteritis (TA) without coronary stenosis. The aim of our study was to evaluate coronary microcirculation in TA using thallium-201 (201Tl) myocardial scintigraphy and dipyridamole (DPM) as vasodilator agent. Twenty-five consecutive patients with TA were prospectively recruited. They were asymptomatic for cardiac issues and examined using 201Tl myocardial scintigraphy at rest and after coronary artery vasodilation with intravenous DPM. Factors associated with improvement in myocardial perfusion after DPM were identified in patients with TA. Among 25 patients with TA, 21 (84%) had 201Tl myocardial perfusion defects and 4 (16%) had normal resting myocardial perfusion. Using a 17-segments model for quantitative image analysis, DPM significantly improved resting 201Tl myocardial perfusion in 14 patients (61%) versus 9 patients without improvement (39%). We were able to examine coronary artery stenoses in 11 patients, including 10 patients with thallium perfusion defects, and significant coronary artery stenoses were present in only 2 patients (18.2%). No significant difference was found in traditional cardiovascular risk factors between TA patients with or without improvement of myocardial perfusion after DPM. The absence of improvement in myocardial perfusion after DPM tended to be closely associated with specific features and prognostic factors of TA, such as aortic regurgitation at diagnosis, renovascular hypertension, longer duration of TA disease, and male sex. We found the significantly high prevalence of myocardial perfusion defects mostly improved after vasodilation with DPM, which may indicate the major role of microcirculatory dysfunction in myocardial ischemia in TA.

Impact of Low‐Dose Dipyridamole Injection on Adenosine Test after Pulmonary Vein Isolation

Dipyridamole increases the levels of extracellular adenosine. The study investigates the impact of low-dose intravenous dipyridamole on adenosine test after pulmonary vein (PV) isolation (PVI). This prospective study included 12 paroxysmal atrial fibrillation (AF) patients (61 ± 12 years; nine men) who underwent PVI at the first procedure. Transient PV reconnection was provoked by adenosine test in 4/48 PVs. In 44 PVs without reconnection, intravenous infusion of low-dose (10 mg) dipyridamole preceded the adenosine test. Additional six patients (PVs) with transient dormant conduction were included. Among the total 10 PVs with transient reconnection, it was eliminated by radiofrequency (RF) application(s) until no dormant conduction was exposed by adenosine test(s) in five PVs. Then, dipyridamole potentiated adenosine test was undertaken to provoke dormant conduction (group 1). In the remaining five PVs, dipyridamole potentiated adenosine test was followed by RF elimination of conduction gap and repeat adenosine test to confirm complete elimination (group 2). Low-dose dipyridamole prolonged the duration of adenosine-induced atrioventricular block without vasodilatatory hypotension. There was no evidence of reconnection in 44 PVs without dormant conduction and in group 1 wherein transient reconnection was eliminated by 4.8 ± 3.2 RF applications in 8.8 ± 3.0 minutes and adenosine injected 3.1 ± 1.8 times. In group 2, dipyridamole plus adenosine test revealed the same dormant conduction that persisted longer than during adenosine alone. It was eliminated by single RF application in 3.4 ± 0.9 minutes, and adenosine was injected once. Low-dose dipyridamole safely prolongs the electrophysiological effects of adenosine test without provoking additional PV reconnection. This allows sustained visualization and facilitates complete RF elimination of the electrical conduction gap.

Cerebrovascular steal phenomenon in a patient undergoing dipyridamole nuclear perfusion cardiac imaging

Transient ischemic neurological deficits following intravenous dipyridamole administration during pharmacological cardiac stress test are seldom reported, but there can be serious vascular complications. We report a case of a 58-year-old Caucasian male who developed expressive aphasia after dipyridamole infusion during an elective dipyridamole-technetium cardiac stress test performed for chest pain. Computed tomography angiogram of the neck revealed a known total occlusion of the right internal carotid artery and 50% stenosis of the left internal carotid artery. The patient's aphasia spontaneously resolved within 24h. In this paper, we report a unique case in which the administration of intravenous dipyridamole precipitated transient ischemic attack in a patient with stable asymptomatic bilateral carotid artery disease and prior carotid endarterectomy. We also discuss the intracerebral vascular steal phenomenon as a possible pathophysiological mechanism in this patient.

Cyanotic Congenital Heart Disease The Coronary Arterial Circulation

Background:The coronary circulation in cyanotic congenital heart disease (CCHD) includes the extramural coronary arteries, basal coronary blood flow, flow reserve, the coronary microcirculation, and coronary atherogenesis.Methods:Coronary arteriograms were analyzed in 59 adults with CCHD. Dilated extramural coronaries were examined histologically in six patients. Basal coronary blood flow was determined with N-13 positron emission tomography in 14 patients and in 10 controls. Hyperemic flow was induced by intravenous dipyridamole pharmacologic stress. Immunostaining against SM alpha-actin permitted microcirculatory morphometric analysis. Non-fasting total cholesterols were retrieved in 279 patients divided into four groups: Group A---143 cyanotic unoperated, Group B---47 rendered acyanotic by reparative surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic before and after operation.Results:Extramural coronary arteries were mildly or moderately dilated to ectatic in 49/59 angiograms. Histologic examination disclosed loss of medial smooth muscle, increased medial collagen, and duplication of internal elastic lamina. Basal coronary flow was appreciably increased. Hyperemic flow was comparable to controls. Remodeling of the microcirculation was based upon coronary arteriolar length, volume and surface densities. Coronary atherosclerosis was absent in both the arteriograms and the necropsy specimens.Conclusions:Extramural coronary arteries in CCHD dilate in response to endothelial vasodilator substances supplemented by mural attenuation caused by medial abnormalities. Basal coronary flow was appreciably increased, but hyperemic flow was normal. Remodeling of the microcirculation was responsible for preservation of flow reserve. The coronaries were atheroma-free because of the salutory effects of hypocholesterolemia, hypoxemia, upregulated nitric oxide, low platelet counts, and hyperbilirubinrmia.

Effects of the Antianginal Drug Trapidil on Atrioventricular Conduction Disturbances During Acute Myocardial Ischemia

Adenosine and related compounds have been shown to produce atrioventricular (AV) conduction block during acute myocardial ischemia. We investigated the effects of the antianginal drug trapidil, which has been shown to inhibit phosphodiesterase, on AV conduction disturbances in a canine model of acute myocardial ischemia. In 35 anesthetized dogs, the AV node artery was cannulated and perfused with arterial blood. Adenosine (300 µg, 650 µg, or 1000 µg) was injected into the AV node artery. With administration of adenosine at 300 µg, 650 µg, or 1000 µg, the atrio-His (AH) interval was increased by 14.6 ms, 22.3 ms, and 29.7 ms, respectively. The effects of adenosine were potentiated by pretreatment with intravenous dipyridamole (250 µg/kg), an inhibitor of adenosine uptake, but the effects of adenosine were attenuated with intravenous trapidil (3 mg/kg), an inhibitor of phosphodiesterase. AV node artery occlusion resulted in prolongation of the AH interval in 4 of 12 dogs. The ischemia-induced AH prolongation was potentiated with intravenous dipyridamole and attenuated with intravenous trapidil. AV conduction disturbances associated with inferior myocardial infarction may be related in part to endogenously released adenosine, and trapidil may be useful in treating AV block associated with acute AV node ischemia.

Hemodynamic response, arrhythmic risk, and overall safety of Regadenoson as a pharmacologic stress agent for myocardial perfusion imaging in chronic obstructive pulmonary disease and bronchial asthma patients

Regadenoson (REG) is a A2a receptor selective pharmacologic SPECT imaging agent. Its safety in unselected chronic obstructive pulmonary disease (COPD) or asthma (AM) undergoing SPECT imaging has not been well evaluated. We retrospectively identified 228 patients (COPD n = 126 and AM n = 102, Grp 1) undergoing REG SPECT from Jan to Nov 2009 and compared to 1,142 patients without COPD and AM (control, Grp 2). A standard 400 μg REG bolus was used and gated Tc-99 m tetrofosmin SPECT done. Patient demographics, REG SPECT data, side effects, arrhythmia occurrences, and any exacerbation of COPD or AM leading to treatment, hospitalization or death were evaluated. The side effect profile of Grp 1 was also compared to a historical cohort who underwent intravenous dipyridamole thallium-201 imaging and adenosine SPECT. Both groups were comparable with regards to baseline characteristics. There was 0% incidence of clinical exacerbation of COPD or AM after REG. COPD patients had more non-significant arrhythmias (58.3% vs. Grp 2, 43%, P = 0.004). There was 0% incidence of any atrio-ventricular block and only 2 instances of brief supraventricular tachycardia. When compared to the historical cohort of COPD who underwent IV dipyridamole thallium imaging, COPD in Grp 1, had more dyspnea and flushing and when compared to COPD/AM patients who underwent adenosine SPECT, Grp 1 pts had more of flushing and headache (24.9% vs. 2.8%, P = <0.001) but less of bronchospasm (1.3% vs. 6.9%, P = 0.022) and AV block (0% vs. 4.2%, P = 0.014). REG SPECT can be safely performed in COPD and AM population.

Effect of diallyl trisulfide on the pharmacokinetics of dipyridamole in rats

This study was aimed to evaluate the effect of diallyl trisulfide (DATS), a major component derived from garlic used to inhibit platelet thromboxane formation, on the pharmacokinetics of dipyridamole. Pharmacokinetic parameters of dipyridamole were determined in rats following intragastric (80 mg/kg suspension or 40 mg/kg solution) or intravenous (3 mg/kg) administration of dipyridamole with coadministration (20 mg/kg) and long-term pretreatment of DATS (10 or 20 mg/kg/day for 15 consecutive days). In addition, everted gut sac models were used to assess transepithelial transport of dipyridamole and the effect of DATS on the intestinal absorption of dipyridamole. After coadministration and long-term pretreatment of DATS, significantly lower Cmax and AUC(0-24 h) were observed for intragastric administration of dipyridamole, whereas little change was noted after intravenous dipyridamole administration. After adding DATS (10 and 50 μg/mL) in the everted gut sacs, absorption of dipyridamole was remarkably decreased in the ileum and jejunum (p < 0.01). In conclusion, DATS reduced the oral exposure of dipyridamole in rats likely by the modification of the dissolution rate and intestinal absorption of dipyridamole, indicating that combined use of DATS or DATS-containing supplements with dipyridamole may require caution as low plasma concentrations of dipyridamole may lead to a subtherapeutic effect of this agent.

Microvascular Function Is Selectively Impaired in Patients With Hypertrophic Cardiomyopathy and Sarcomere Myofilament Gene Mutations

The purpose of this study was to assess myocardial blood flow (MBF) using positron emission tomography in patients with hypertrophic cardiomyopathy (HCM) according to genetic status. Coronary microvascular dysfunction is an important feature of HCM, associated with ventricular remodeling and heart failure. We recently demonstrated the increased prevalence of systolic dysfunction in patients with HCM with sarcomere myofilament gene mutations and postulated an association between genetic status and coronary microvascular dysfunction. Maximum MBF (intravenous dipyridamole, 0.56 mg/kg; Dip-MBF) was measured using (13)N-labeled ammonia in 61 patients with HCM (age 38 ± 14 years), genotyped by automatic DNA sequencing of 8 myofilament-encoding genes (myosin-binding protein C, beta-myosin heavy chain, regulatory and essential light chains, troponin T, troponin I, troponin C, alpha-tropomyosin, and alpha-actin). In 35 patients, cardiac magnetic resonance imaging was performed. Fifty-three mutations were identified in 42 of the 61 patients (genotype positive; 69%). Despite similar clinical profiles, genotype-positive patients with HCM showed substantially lower Dip-MBF compared with that of genotype-negative patients (1.7 ± 0.6 ml/min/g vs. 2.4 ± 1.2 ml/min/g; p < 0.02). A Dip-MBF <1.5 ml/min/g had 81% positive predictive value for genotype-positive status and implied a 3.5-fold independent increase in likelihood of carrying myofilament gene mutations (hazard ratio: 3.52; 95% confidence interval: 1.05 to 11.7; p = 0.04). At cardiac magnetic resonance imaging, the prevalence of late gadolinium enhancement was greater in genotype-positive patients (22 of 23 [96%] compared with 8 of 12 [67%] genotype-negative patients; p = 0.038). Patients with HCM with sarcomere myofilament mutations are characterized by more severe impairment of microvascular function and increased prevalence of myocardial fibrosis, compared with genotype-negative individuals. These findings suggest a direct link between sarcomere gene mutations and adverse remodeling of the microcirculation in HCM, accounting for the increased long-term prevalence of ventricular dysfunction and heart failure in genotype-positive patients.

Dipyridamole-Associated Shock and Pulmonary Edema

To report a case of fulminant shock and noncardiogenic pulmonary edema induced by intravenously administered dipyridamole. A 73-year-old woman presented to the office of her cardiologist for dipyridamole myocardial scintigraphy. Several minutes after administration of intravenous dipyridamole 0.57 mg/kg over 4 minutes she developed wheezing, followed by cardiovascular collapse and pulmonary edema requiring 100% oxygen and endotracheal intubation. She had never received dipyridamole before this, and no other medications or exposures were documented proximate to the collapse. On transfer to the hospital, she developed shock refractory to multiple vasopressors, which responded to continuous infusions of epinephrine. She also had severe pulmonary edema requiring invasive ventilation, 100% inspired oxygen, and 24 cm H₂O positive end-expiratory pressure. An echocardiogram did not show new left-ventricular dysfunction and there were signs of right-heart underfilling, supporting a diagnosis of noncardiogenic pulmonary edema. Both shock and pulmonary edema resolved within 12 hours. Dipyridamole-associated hypotension has been reported in a number of case series and registries. Detailed case descriptions, however, are not available in the literature to permit understanding of the mechanism of shock following hypotension resulting from dipyridamole myocardial scintigraphy. Our case is exceptional in that echocardiography results support a diagnosis of hypovolemic (rather than cardiogenic) shock. To our knowledge, this is the first case of severe (most likely noncardiogenic) pulmonary edema associated with intravenous infusion of dipyridamole. An objective causality assessment suggested that this patient's cardiopulmonary collapse was probably related to dipyridamole. While hypotension has been previously associated with intravenous use of dipyridamole, ours is the first report to suggest a noncardiogenic mechanism for shock. To our knowledge, this is the first reported case of noncardiogenic pulmonary edema following dipyridamole infusion.

Effect of Intravenous Dipyridamole on Coronary Flow Parameters in Patients with Isolated Coronary Artery Ectasia: Assessment by Transesophageal Echocardiography

In a prospective study design, we sought to assess the effect of dipyridamole on coronary flow parameters in patients with isolated coronary artery ectasia (CAE) as compared to subjects with normal coronaries. We enrolled 30 patients with ectasia of the left anterior descending (LAD) artery (study group), and 10 subjects with normal coronaries (control group). All subjects underwent transesophageal echocardiography to record flow velocities in the proximal LAD coronary artery, and velocity time integrals were calculated. The diameter of the proximal LAD coronary artery was measured and flow was calculated. Dipyridamole (0.56 mg/kg) was administered intravenously and measurements were repeated 5 minutes later. At baseline, systolic and diastolic velocities, systolic, diastolic, and total velocity time integrals were significantly higher in the control group (P < 0.05 for all), yet, systolic, diastolic, and total coronary flow were significantly higher in the study group (P < 0.05 for all). Following dipyridamole administration, systolic, diastolic, and total coronary flow were still significantly higher in the study group (P < 0.05 for all), yet, there was no significant difference between the two groups regarding the other parameters, and regarding coronary reserve values (P > 0.05 for all). We concluded that patients with isolated CAE have a higher resting coronary flow as compared to control subjects with normal coronaries. Intravenous dipyridamole administration in these patients maintained a significantly higher coronary flow, with a coronary flow reserve similar to controls.