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The exercise electrocardiographic stress test (ExET) is the most widely used non-invasive diagnostic method to detect coronary artery disease. However, the sole ST depression criteria (ST-max) have poor specificity for coronary artery disease in patients with left ventricular hypertrophy. We hypothesised that ST-segment depression/heart rate hysteresis, depicting the relative behaviour of ST segment depression during the exercise and recovery phase of the test might increase the diagnostic accuracy of ExET for coronary artery disease detection in such patients.In three cardiology centres, we studied 113 consecutive patients (mean age 66 ± 2 years; 88% men) with hypertension-related left ventricular hypertrophy at echocardiography, referred to coronary angiography after an ExET. The following ExET criteria were analysed: ST-max, chronotropic index, heart rate recovery, Duke treadmill score, ST-segment depression/heart rate hysteresis.We detected significant coronary artery disease at coronary angiography in 61 patients (53%). At receiver-operating characteristic analysis, ST-segment depression/heart rate hysteresis had the highest area under the curve value (0.75, P 0.001 when compared with the 'neutral' receiver-operating characteristic curve value of 0.5). Area under the curve values were 0.68 (P 0.01) for the chronotropic index, 0.58 (P = NS) for heart rate recovery, 0.57 (P = NS) for ST-max and 0.52 (P = NS) for the Duke treadmill score.Among currently available ExET diagnostic variables, ST-segment depression/heart rate hysteresis offers a substantially better diagnostic accuracy for coronary artery disease than conventional criteria in patients with hypertension-related left ventricular hypertrophy.

Background Based upon the results of a previous small pilot study, we present the results of a prospective single-center randomized study comparing the performance of the implantable loop recorder (ILR) at two implanting sites. Methods A group of patients whose ILRs were implanted via a left axillary approach were compared with a group who received an ILR in the traditional left site of the chest. Follow-up (FU) was scheduled every 6 months or when symptoms occurred. All patients enrolled in the study had a complete FU from implantation to explantation. R- and P-wave amplitudes were measured at implantation and during FU. Explantation of the device was programmed at the end of service life or when ILR analysis resulted in a complete and exhaustive diagnosis. Results Sixty-three patients were enrolled (70 ± 12 years, range: 21–92, 59% male): 31 standard and 32 with axillary access. The R-wave amplitude obtained with the new technique was comparable with that obtained with the standard procedure. The diagnostic accuracy of the ILR was comparable in the two groups. The axillary implantation procedure was slightly longer but no complications were observed. Conclusion This long-term randomized study confirmed that axillary access for ILR implantation is feasible, safe, well tolerated, and reliable in terms of device performance. Moreover, it is aesthetically superior to the standard approach and carries the potential of minimizing permanent scarring after ILR extraction.

Aims Incidence of primary cardiac tumors (PCTs) is not known. Literature data derive from autoptic studies or echocardiographic registries. An incidence of 1 of 1000 autoptic and 1.5 of 1000 echocardiographic study is reported but data from a general population are not available. The aim of our study was to evaluate the incidence rate of PCTs in the general population. Methods All patients with suspected cardiac mass were evaluated with basal echocardiogram and/or transesophageal echocardiogram/cardiac magnetic resonance by Grosseto's cardiology department, the county referral center for both adult and pediatric populations. Diagnosis was confirmed at surgical excision (32), autoptic specimens (3) or by multimodal imaging when surgery was not indicated (7). The database of the county health system was interrogated to identify residents with The International Classification of Diseases-9 codes of PCT. Forty-two consecutive cases of PCTs were diagnosed from 1 January 1998, through 31 December 2011, among residents in Grosseto's county. Results Incidence rate of PCTs was 1.38 of 100,000 inhabitants per year. PCTs were benign in 38 patients (90.5%) and malignant in four (9.5%). Twenty myxomas were found (48%), followed by seven fibroelastomas (15%), six lipomas (15%), three rhabdomyomas (8%), two hemangioma (5%), two sarcomas (5%), one lymphoma (2%) and one pericardial hemangiopericytoma (2%). Incidence of benign PCT was 1.24 of 100,000/year; referring only to myxomas we found an incidence of 0.68 of 100,000/year. Conclusion This is the first population study on PCT, a rare disease with an incidence rate of 1.38 new cases per 100,000 residents per year.

Pocket hematoma is a common complication of cardiac implantable electronic device procedures and a potential risk factor for device infections, especially in patients on oral anticoagulation or antiplatelet treatment. There is a wide variability in the incidence of pocket hematoma and bleeding complications in the literature and the major cause for this seems to be the variability of the used definitions for hematomas. The lack of generally accepted definition for pocket hematoma renders the comparisons across the studies difficult. In this article, we briefly review the current literature on this issue and propose a uniform definition for pocket hematoma and criteria for grading the severity of hematoma in clinical practice and research.

Aims Prevalence of left appendage thrombosis ranges from 6 to 18% in persistent atrial fibrillation (AF). Few and low sample size studies have assessed left and right atrial thrombosis in persistent atrial flutter (AFL) and a wide variety of frequencies, from 1 to 21%, has been reported. The aim of this study was to evaluate the prevalence of atrial appendage thrombosis in a large population of patients undergoing transoesophageal echocardiography (TEE)-guided cardioversion (CV) for recent AFL onset and compare it with AF. Methods and results From 1999 to September 2014, we collected data of 1081 patients to CV: 877 affected by AF (81.1%) and 204 by AFL (18.9%). The presence of auricular thrombosis was evaluated by TEE in AF or AFL persisting for more than 48 h. The presence of appendage thrombosis, Doppler emptying velocities, and severe spontaneous echo contrast (SEC) was studied. The overall prevalence of atrial thrombosis was 9.62% (104/1081). Frequency of atrial thrombosis in AFL patients was 6.4% (13/204) vs. 10.5% among AF (92/877), P = 0.074. Comparing the two appendages, frequency of left atrial appendage thrombosis was in AFL 5.9% (12/204) vs. 9.9% (87/877) in the AF group, P = 0.07. Right atrial appendage thrombosis was present in 0.5% (1/204) in the AFL group vs. 0.8% (7/877) in the AF group, P = 0.64. Moderate to severe SEC (3+/4+) was present in 28% of AFL patients (57/204) vs. 35% of AF patients (307/877), P = 0.05. Conclusion Auricular thrombosis is not an infrequent finding in AFL before CV. Our study suggests the use of TEE screening in AFL, as well as in AF, when patients arrive to clinical attention after more than 48 h from arrhythmia onset.

A 62-year-old man admitted for presyncope presented two symptomatic sustained ventricular tachycardia with right bundle branch morphology and inferior axis suggesting a pathology of the left ventricular lateral wall, the site where Cardiac Magnetic Resonance demonstrated a thinned, hypokinetic segment with fibro-fatty subepicardial infiltration. A very localized Left Dominant Arrhythmogenic Cardiomyopathy was diagnosed and an ICD implanted.

Bivalirudin is widely used as an anticoagulant during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction. However, an increase in acute stent thrombosis rates has been found in the HORIZONS-AMI trial. A prolonged infusion after PCI has been shown to be a safe and effective tool in patients undergoing urgent or elective PCI in the PROBI VIRI study. We examined the effects of prolonged drug infusion after primary PCI. From databases of 5 high-volume centers we compared a group of patients treated with a 4-hour prolonged infusion after PCI to 2 groups treated with a peri-PCI infusion and heparin plus abciximab. The primary study end point was >70% ST-segment resolution within 90 minutes after PCI; secondary end points were partial (>50%) ST-segment resolution within 90 minutes and intrahospital major and minor bleedings on the Acuity scale. The study population consisted of 264 patients undergoing primary PCI who were pretreated with aspirin and clopidogrel. The 3 study groups did not differ significantly by baseline characteristics. The primary end point was achieved in 69.8%, 48.8%, and 69.6% of patients in the prolonged bivalirudin, bivalirudin, and heparin/abciximab groups, respectively (p = 0.048 for prolonged vs standard infusion, p = 0.98 for prolonged infusion vs abciximab). Major bleedings and other secondary study end points were not significantly different among study groups. In conclusion, a strategy of prolonged bivalirudin infusion after primary PCI seems equivalent to a strategy with heparin plus abciximab, with an improvement in standard infusion in obtaining early microvascular reperfusion.

Background: Drug eluting stent (DES) use has improved clinical outcome after percutaneous coronary interventions. However, DES-treated patients may have a higher risk of stent thrombosis, mainly due to uncorrect stent deployment or lack of reendothelialization. Thus, the availabilily of different approaches with comparable efficacy to DES, but higher safety, especially in bleeding-prone patients, have to be investigated. Study Design: The EREMUS is a multicenter open-label prospective randomized three-arm clinical trial that will investigate the efficacy of a paclitaxel coated balloon + an endothelial progenitor capture stent for the treatment of native coronary lesions, and compare it to a DES strategy, or the sole endothelial progenitor capture stent. An angiographic follow-up with optical coherence tomography analysis will be scheduled 9 months after index procedure. Noninferiority regarding the primary endpoint (late luminal loss) between study group and DES is hypothesized. All patients will undergo clinical follow-up until 24 months from index hospitalization. Conclusions: The EREMUS trial will determine whether a composite approach with a paclitaxel coated balloon + an endothelial progenitor capture stent in coronary lesions at medium-to-high risk of restenosis will achieve similar results compared to DES regarding inhibition of intrastent proliferation; complete stent strut reendothelialization, a safety issue, will also be investigated. © 2011 Wiley-Liss, Inc.

OBJECTIVE Bivalirudin, a direct thrombin inhibitor, provides similar ischemic outcomes with significantly less major bleeding compared with unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients undergoing percutaneous coronary interventions (PCI). Although the approved labeling for bivalirudin allows for low-dose prolonged postprocedure administration, this practice is not routine. Therefore, we sought to evaluate the safety and efficacy of longer post-PCI infusion. METHODS From our database, we retrospectively compared two groups of patients with acute coronary syndrome undergoing complex PCI, one group treated with UFH+GPI (n = 59) and another with a periprocedural and post-PCI bivalirudin infusion for 4 h (n = 50). Endpoints included periprocedural myocardial infarction (MI), 30-day major adverse cardiac events, and in-hospital major and minor bleeding. RESULTS There were no significant differences in the baseline and procedural characteristics of the two groups; most patients (approximately 90%) had complex coronary lesions (the American College of Cardiology/American Heart Association type B2/C). There was no significant difference in the rates of periprocedural MI (11.9 vs. 8.0%, P = NS) or 30-day major adverse cardiac events (8.5 vs. 6.0%, P = NS) among patients treated with UFH+GPI or bivalirudin. However, patients who received bivalirudin had significantly lower rates of minor bleeding (20.3 vs. 4.0%, P

The number of cardiac implantable electronic device (CIED) proce-duresisdramaticallyincreasingworldwide[1].Upto37–46%ofpatientsrequiringdevicesurgeryareonchronicoralanticoagulation(OAC)ther-apy [2]. Perioperative anticoagulation managementrepresentsadilem-mafor physicians, particularly in the subset of patients with moderate-to-high risk of arterial thromboembolic events. Current guidelinesrecommend interruption of anticoagulation and bridging with heparin[3]. However, such strategy has been associated with increased risk ofpocket hematoma(up to 20%) [4]. More recently, observational studiesshowed that continuing warfarin for cardiac rhythm device implanta-tion is safe and is associated with lower incidence of pocket hematoma[5,6]. Noteworthy, evidence from randomized controlled studies con-firmed the efficacy and safety of uninterrupted OAC as compared withheparin bridging [7,8]. Although uninterrupted OAC is associated withreduced bleeding, a large proportion of patients remain exposed to asubstantialriskofhemorrhagiccomplications.Preventionofhematomaformation duringCIEDsurgery is animportant challenge nowadays. In-deed,pockethematomarepresentsoneofthemainriskfactorsforlocaland systemic device-related infections, leading to increased patientmorbidity and health care costs [9,10]. To further reduce bleeding riskin this setting, some experts suggest that CIED procedures should beperformed within the safest INR ranges, thus maintaining INR valuesas low as possible, according to the type of procedure [11]. However, asystematic assessment of intrinsic bleeding risk is lacking in patientswith uninterrupted OAC undergoing CIED surgery. Therefore, the iden-tification of patients at higher bleeding risk would be advantageous tooptimize perioperative management. In recent years, the bleedingscores HASBLED, ATRIA and HEMORR

Atrial fibrillation (AF) and atrial flutter (AFL) are strong atrial thrombosis (THR) risk factors. In recent-onset tachyarrhythmias, the incidence of left atrial appendage (LAA) THR, detected by transesophageal echocardiography (TEE), has been widely studied, ranging from 6% to 18% (AF) and 4% to 11% (AFL). On the contrary, few studies have assessed right atrial appendage (RAA) THR, and there is no information on the relation between the RAA flow characteristics and the presence of RAA THR. The aims of this study were to evaluate the incidence of RAA THR in a population of patients undergoing TEE-guided cardioversion for recent-onset atrial tachyarrhythmias and to analyze RAA Doppler flow and its relation to thrombus formation.From 1998 to 2012, patients admitted to the emergency department for persistent, non-self-terminating atrial tachyarrhythmia lasting2 days who gave informed consent for TEE-guided cardioversion were prospectively enrolled in the study. Among 1,042 patients, complete anatomic and functional studies of the LAA and RAA were feasible in 983 (AF, n = 810 [23%]; AFL, n = 173 [5%]). The presence of RAA and LAA THR, appendage emptying velocities, and the presence of severe spontaneous echocardiographic contrast were studied.The overall incidence of atrial THR was 9.7% (96 of 983). The incidence of THR was 9.3% (91 of 983) in the LAA and 0.73% (seven of 983) in the RAA (P .01). In the AF and AFL groups, the incidence of LAA THR was 10.3% (83 of 805), compared with 0.75% (six of 805) for RAA THR (P .01). Among patients with AFL, the incidence of LAA THR was 6% (10 of 178), compared with 0.6% (one of 178) for RAA THR (P .01). The mean LAA peak emptying velocity was 24 cm/sec (range, 10-32 cm/sec) in patients with LAA THR, compared with 38 cm/sec (range, 20-59 cm/sec) in those without THR; the mean RAA peak emptying velocity was 17 ± 7 cm/sec in patients with RAA THR, compared with 34 ± 13 cm/sec in those without THR (P .001).RAA thrombi are significantly less frequent than LAA thrombi but may reach large dimensions. Multiplane TEE allows RAA morphologic and functional assessment. Before TEE-guided cardioversion, both the LAA and the RAA must be routinely studied.

AIMS Comparing the nephrotoxicity of individual contrast agents is challenging, as contrast-induced acute kidney injury (CI-AKI), a widely used trial endpoint, is unable to discriminate between contrast-related and contrast-unrelated causes of renal damage. We established a quantitative method to selectively evaluate the dose-dependent nephrotoxic effect of different contrast agents. METHODS We randomized 113 patients undergoing coronary procedures to either iodixanol 320 mg/ml or iobitridol 350 mg/ml. We calculated baseline creatinine clearance (CrCl) and postprocedural change in serum creatinine. We then calculated the regression of the individual iodine load against the creatinine maximum change [load-to-damage relationship (LDR)]. We assumed that its R estimates the predictive accuracy of contrast dose-dependent effects on renal function changes, and that the slope of the LDR characterizes the intrinsic nephrotoxicity of the contrast. We also performed a semi-quantitative evaluation of procedural complexity to assess its complementary role in postprocedural AKI. RESULTS We found significant correlations between contrast load and creatinine changes for both iobitridol (R: 0.29; P

Objectives. This study sought to assess the value of dipyridamole echocardiography in predicting reinfarction in patients evaluated early after uncomplicated acute myocardial infarction. Background. The identification of future nonfatal reinfarction seems an elusive target for physiologic testing. However, a large sample population is needed to detect minor differences in phenomena with a low event rate. Methods. We assessed the value of dipyridamole echocardiography in predicting reinfarction in 1,080 patients (mean [±SD] age 56 ± 9 years; 926 men, 154 women) evaluated early (10 ± 5 days) after uncomplicated acute myocardial infarction and followed up for 14 ± 10 months. Results. Submaximal studies due to limiting side effects occurred in 14 patients (1.3%); these test results were included in the analysis. Results of dipyridamole echocardiography were positive in 475 patients (44%). During follow-up, there were 50 reinfarctions: 45 nonfatal, 5 fatal (followed by cardiac death ≤4 days after reinfarction). Reinfarction (either nonfatal or fatal) occurred in 30 patients with positive and 20 with negative results (6.3% vs. 3.3%, p Conclusions. Dipyridamole echocardiographic positivity identifies patients evaluated early after uncomplicated acute myocardial infarction at higher risk of reinfarction, especially fatal reinfarction.

A reduced coronary flow reserve (CFR) has been demonstrated in diabetes, but the underlying mechanisms are unknown. We assessed thermodilution-derived CFR after 5-min intravenous adenosine infusion through a pressure-temperature sensor-tipped wire in 30 coronary arteries without significant lumen reduction in 30 patients: 13 with and 17 without a history of diabetes. We determined CFR as the ratio of basal and hyperemic mean transit times (Tmn); fractional flow reserve (FFR) as the ratio of distal and proximal pressures at maximal hyperemia to exclude local macrovascular disease; and an index of microvascular resistance (IMR) as the distal coronary pressure at maximal hyperemia divided by the inverse of the hyperemic Tmn. We also assessed insulin resistance by the homeostasis model assessment (HOMA) index. FFR was normal in all investigated arteries. CFR was significantly lower in diabetic vs. nondiabetic patients [median (interquartile range): 2.2 (1.4–3.2) vs. 4.1 (2.7–4.4); P = 0.02]. Basal Tmn was lower in diabetic vs. nondiabetic subjects [median (interquartile range): 0.53 (0.25–0.71) vs. 0.64 (0.50–1.17); P = 0.04], while hyperemic Tmn and IMR were similar. We found significant correlations at linear regression analysis between logCFR and the HOMA index ( r2 = 0.35; P = 0.0005) and between basal Tmn and the HOMA index ( r2 = 0.44; P < 0.0001). In conclusion, compared with nondiabetic subjects, CFR is lower in patients with diabetes and epicardial coronary arteries free of severe stenosis, because of increased basal coronary flow, while hyperemic coronary flow is similar. Basal coronary flow relates to insulin resistance, suggesting a key role of cellular metabolism in the regulation of coronary blood flow.

Objectives. This study was conducted to assess the feasibility, safety and prognostic value of dipyridamole echocardiography in elderly patients recovering from an uncomplicated acute nyocardial infarction in a subset analysis performed on the patients entered in the subproject “residual ischemia” of the Echo Persantine Italian Cooperative Study (EPIC). Background. Coronary heart disease accounts for two thirds of all deaths in the age group >65 years, and >50% of all patients admitted to the hospital with acute myocardial infarction are >65 years old. The prognostic value of dipyridamole-induced left ventricular dysfunction was clearly established in patients evaluated early after acute infarction. Methods. In a subgroup analysis of the Echo Persantine Italian Cooperative Study (EPIC), we assessed the value of dipyridamole echocardiography in predicting cardiac events in 190 elderly (≥65 years) patients (age 68.4 ± 3.3 years, range 65 to 78; 147 men and 43 women) evaluated early (mean 10 days) after uncomplicated acute myocardial infarction and followed up for 14 ± 9.8 months. Results. There was no major side effect during dipyridamole echocardiography. A positive test result occurred in 85 patients (44.7%). During follow-up, there were 62 events (14 cardiac deaths, 7 nonfatal reinfarctions, 21 cases of class III or IV angina and 20 revascularization procedures). Of these 62 events, 44 occurred among 85 patients with positive dipyridamole echocardiography and 18 among 105 patients with negative dipyridamole echocardiography (52% vs. 17%, p < 0.001). Spontaneous events (death, reinfarction, angina) occurred in 31 patints with positive and in 11 with negative dipyridamole echocardiography (36% vs. 10%, p < 0.001). Hard events (myocardial infarction or death) occurred in 14 patients with positive and 7 with negative dipyridamole echocardiography (16% vs. 6%, p < 0.05). Death occurred in 11 patients with positive and in 3 with negative dipyridamole echocardiography (13% vs. 3%, p < 0.01). The positive predictive value of positive dipyridamole echocardiography and negative predictive value of negative dipyridamole echocardiography as related to the occurrence of all events in the follow-up period (death, reinfarction, angina, revascularization procedures) were 52% and 83%, respectively. The relative risk (that is, the relative risk of occurrence of future cardiac events in the group with positive dipyridamole echocardiography compared with that in those with negative dipyridamole echocardiography) was 3 for all events and 4.4 for death. Conclusions. Dipyridamole echocardiography was well tolerated by elderly patients and proved to be very effective in prognostic stratification early after uncomplicated acute myocardial infarction, even when only survival was considered.

purpose: To determine the prognostic capability of the dipyridamole echocardiography test (DET) early after an acute myocardial infarction. patients and methods: On the basis of 11 different echocardiographic laboratories, all with established experience in stress echocardiography and fulfilling quality-control requirements for stress echocardiographic readings, 925 patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. results: During the follow-up, there were 34 deaths and 37 nonfatal myocardial infarctions; 104 patients developed class III or IV angina and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction, and death), the most important univariate predictor was the presence of an inducible wall motion abnormality after dipyridamole administration (χ2 = 45.8). With a Cox analysis, echocardiographic positivity, age, and male gender were found to have an independent and additive value. Considering survival (and, therefore, death as the only event), age was the most meaningful parameter, followed by the wall motion score index during dipyridamole administration (χ2 = 12.1). Among other parameters, the resting wall motion score index was a significant predictor of death. In a multivariate analysis, the prognostic contributions of age (relative risk estimate = 1.08) and wall motion score index during dipyridamole administration (relative risk estimate = 4.1) were independent and additive. In particular, considering death only, the event rate was 2 % in patients with negative DET results, 4% in patients with positive high-dose DET results, and 7% in patients with positive low-dose DET results. conclusions: DET is feasible and safe early after uncomplicated myocardial infarction and allows effective risk stratification on the basis of the presence, severity, extent, and timing of the induced dyssynergy.

Background Percutaneous coronary intervention (PCI) of small vessels is limited by an increased risk of restenosis and adverse outcome, even when drug-eluting stents (DES) are employed. In recent years, the paclitaxel-coated balloon (PCB) has been shown to reduce neointimal proliferation and the need for target lesion revascularization (TLR) in an in-stent restenosis setting. The impact of a PCB during PCI of small coronary vessels was evaluated and compared to one of the most widely used DES. Methods In the PICCOLETO randomised clinical trial, patients with stable or unstable angina undergoing PCI of small coronary vessels (≤2.75 mm) were randomised to Dior PCB (28 patients) or Taxus DES (29 patients). The primary study end point was per cent diameter stenosis at 6-month angiographic follow-up (non-inferiority), secondary end points were angiographic binary restenosis and occurrence of major adverse cardiac events (MACE: death, Q-wave myocardial infarction, TLR) at 9 month follow-up. Results The two groups were not dissimilar regarding clinical and angiographic characteristics. Study was interrupted after enrolment of two-thirds of patients due to a clear superiority of one study group. The primary end point was not met, because the PCB group showed higher per cent diameter stenosis (43.6% vs 24.3%, p=0.029); angiographic restenosis was higher as well (32.1 vs 10.3%, p=0.043), whereas MACE were 35.7% in the PCB group and 13.8% in the DES group (p=0.054). Conclusions Dior PCB failed to show equivalence to Taxus DES regarding angiographic end points during PCI of small coronary arteries. Clinical Trial Registration Number (EudraCT code) 2009-012268-15.

Background: We compared the clinical course of 10 patients who received an implantable loop recorder (ILR) at a traditional site with 11 patients whose ILRs were implanted via a subpectoral site via a left axillary approach without complications. Methods and Results: R-wave amplitude was determined at implantation and during follow-up. Each patient was followed after 7 days to optimize device setting and then at 1 and 3 months. The R-wave amplitude obtained with the new technique was significantly higher and more stable than that obtained with the standard procedure. Our preliminary experience suggests that axillary access for ILR implantation is feasible, safe, well tolerated, and reliable in terms of sensing function and device performance. Moreover, it is superior aesthetically to the standard approach and carries the potential of minimizing permanent scarring after ILR extraction. (PACE 2010; 999–1002)

Modern antithrombotic strategies for patients undergoing percutaneous coronary interventions (PCIs) must take into account the risk of ischemic and hemorrhagic complications. Bivalirudin decreases the risk of hemorrhagic complications after PCI; however, concerns have been raised about its efficacy in preventing ischemic complications. We evaluated the effectiveness of a prolonged intra- and postprocedural bivalirudin infusion versus a standard regimen in preventing PCI-related myocardial damage. One hundred seventy-eight consecutive patients with stable or unstable angina and complex coronary anatomy were enrolled in this single-center, randomized, single-blinded study. Patients were randomized to bolus plus bivalirudin infusion during PCI (n = 90) or bolus plus bivalirudin infusion during and after PCI (4 hours, n = 88). The primary end point was incidence of periprocedural myocardial damage (creatine kinase-MB increaseor=3 times upper limit of normal). Secondary end points were 30-day and 6-month major adverse cardiovascular events (death, new Q-wave myocardial infarction, target vessel revascularization) and in-hospital bleeding (major/minor). The 2 groups did not differ significantly in baseline and procedural characteristics. The primary end point of the study was significantly less frequent in the prolonged infusion group (6.8% vs 16.7%, p = 0.041). No significant differences for secondary end points were observed. In conclusion, in patients undergoing complex PCI, a prolonged bivalirudin infusion after PCI compared to an intraprocedural-only regimen significantly decreased the incidence of periprocedural myocardial damage.

Natali A, Vichi S, Landi P, Toschi E, Severi S, L’Abbate A, Ferrannini E (C.N.R. Institute of Clinical Physiology and the University of Pisa, Pisa, Italy). Coronary artery disease and arterial hypertension: clinical, angiographic and follow-up data. J Intern Med 2000; 247: 219–230. Objectives. To evaluate how the presence of arterial hypertension affects coronary atherosclerosis and prognosis in patients with, or at high risk of, ischaemic heart disease. Design. Retrospective analysis of clinical records and follow-up data. Settings. Single referral centre for ischaemic heart disease. Subjects. All consecutive patients (n = 1700, 38% with hypertension) undergoing coronary angiography for the evaluation of ischaemic heart disease during 1983–92. Results. On angiography, the likelihood of having three-vessel disease was higher amongst hypertensives (odds ratio = 1.41; 95% confidence interval [CI] = 1.08–1.85) after adjustment for age, sex, and angina symptoms. The sum of all visible stenoses (an index of overall atherosclerotic involvement) was 19% higher in hypertensives (262 ± 204 vs. 220 ± 194 units, P

Aims/hypothesis. Prevalence and incidence of coronary heart disease (CHD) are increased in patients with Type II (non-insulin-dependent) diabetes mellitus; whether this is entirely due to more extensive coronary atherosclerosis is, however, controversial. Methods. We analysed the clinical, angiographic and follow-up data of 2253 consecutive patients undergoing coronary angiography over the decade 1983–1992. Results. Abnormal coronary arteries (≥ 50 % stenosis) were found more frequently in diabetic than in non-diabetic subjects (85 vs 67 %, p < 0.0001), the excess being explained by a higher prevalence of three-vessel disease (36 vs 17 %, p < 0.0001). The sum of all angiographically detectable lumen stenoses (atherosclerosis score, ATS) was higher in diabetic than in non-diabetic subjects (352 ± 232 vs 211 ± 201 units, p < 0.0001). After adjusting for measured cardiovascular risk factors, diabetes was still associated with an excess ATS (114 units in men and 187 units in women, p < 0.0001 for both, p < 0.03 for the interaction ATS x sex). Within the diabetic group, the only variable that was independently (of sex and age) associated with ATS was serum cholesterol, whereas plasma glucose concentration, disease duration and type of treatment were not correlated with the severity of coronary atherosclerosis. In contrast, clinical grade proteinuria was not associated with a more diffuse coronary atherosclerosis either in diabetic (366 ± 243 vs 354 ± 233 units) or non-diabetic subjects (231 ± 201 vs 207 ± 197 units). Over a mean follow-up period of 88 months, 19 % of diabetic patients compared with 10 % of non-diabetic patients died of a cardiac cause (age and sex-adjusted odds ratio OR = 1.34 [1.14–1.57]). In a Cox model adjusting for age, sex and all major risk factors, diabetes was still associated with a significant excess risk of dying of a cardiac cause (OR = 1.37 [1.14–1.60]); this excess was similar to, and independent of, that carried by the presence of prior myocardial infarction in the whole population (OR = 1.42 [1.25–1.62]). Proteinuria was associated with a higher risk of cardiac death, particularly in diabetic patients, independently of coronary atherosclerosis (adjusted OR = 1.46 [1.03–1.99]). Conclusion/interpretation. In patients undergoing angiography, diabetes, especially in women, is associated with more severe and diffuse coronary atherosclerosis which is not explained by either the traditional risk factors or the presence of proteinuria. On follow-up, these patients experience an excess of cardiac deaths, to which coronary atherosclerosis and proteinuria make independent, quantitative contributions. [Diabetologia (2000) 43: 632–641]

Although effective in reducing the total embolic burden, many current thrombectomy devices might not be able to prevent the liberation of plaque components, which have been shown to be a potential contributor to the development of no-reflow during primary percutaneous coronary intervention.

The identification of future reinfarction seems an elusive target for physiologic testing, consistently with the accepted notion that it is plaque type, rather than plaque size, that matters in provoking coronary occlusion. However, large sample populations are needed to detect phenomena with a low event rate. In addition, one should employ noninvasive stress test results that are tightly related to the extent and severity of CAD — in a stronger way than exercise-ECG. Aim of this study was to assess the capability of dipyridamole echocardiography test (DET) to predict reinfarction in patients evaluated early after acute uncomplicated myocardial infarction. In an updated analysis of the EPIC Study, we assessed the value of DET in predicting reinfarction in 1080 pts (age = 56 ± 9, 926 men and 154 women) evaluated early (10 ± 5 days) after uncomplicated acute myocardial infarction and followed up for 14 ± 10 months. A positive test occurred in 475 pts (44%). During follow-up, there were 50 reinfarctions: 45 non-fatal, and 5 fatallfollowed by cardiac death after ≤ 4 days from the reinfarction). Reinfarction (either nonfatal or fatal) occurred in 30 pts with positive and in 20 with negative DET (6.3 vs 3.3%, p l 0.01). Nonfatal reinfarction occurred in 25 patients with positive and in 20 with negative DET (5 vs 3%, P = 0.05). Reinfarction was fatal in 5 out of 25 reinfarcted patients with positive and in none out of 20 reinfarcted patients with negative DET (20 vs 0%, P = 0.07). The relative risk (i.e., the relative risk of the occurrence of future cardiac events in the group with negative DET) of reinfarction was 1.9. In conclusion, DET positivity identifies patients evaluated early after uncomplicated myocardial infarction at higher risk of reinfarction and especially of fatal reinfarction.

BACKGROUND Before any new diagnostic test is accepted in clinical practice, such a test should be compared with established diagnostic tools in an appropriately large series of patients encompassing the complete spectrum of challenges to which the test is exposed. The aim of the present study was to assess the relative diagnostic and prognostic accuracies of high-dose dipyridamole echocardiography (two-dimensional echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg over 10 hours) versus maximal symptom-limited bicycle exercise ECG test in patients with angina. METHODS AND RESULTS We studied 429 consecutive in-hospital patients who met the following inclusion criteria: history of chest pain, off antianginal therapy for at least 2 days (1 week for beta-blockers), no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction (akinesis or dyskinesis) at baseline, and acceptable acoustic window under resting conditions. All patients underwent dipyridamole echocardiography and exercise ECG--on different days and in random order--within 1 week of coronary angiography (which was performed independent of test results) and were followed up for 37.8 +/- 14 months (range, 1 to 73 months). Criteria of positivity were for dipyridamole echocardiography, a transient regional dyssynergy absent in the baseline examination; for exercise ECG, an ST-segment shift of > or = 0.1 mV from baseline; and for coronary angiography, a luminal reduction of > or = 75% in at least one major coronary vessel (50% for left main). There were 183 patients without and 246 with coronary artery disease; 132 had one-, 70 had two-, and 44 had three- and/or left main vessel disease. The specificity was higher for dipyridamole echocardiography than for exercise ECG (90% versus 51%, P < .001). The overall sensitivity of dipyridamole echocardiography was similar to that of exercise ECG (75% versus 74%, P = NS), with no significant differences in the subset with one- (67% versus 69%, P = NS), two- (79% versus 77%, P = NS), or three- (93% versus 86%, P = NS) vessel disease. During the follow-up, there were 20 deaths, 13 nonfatal myocardial infarctions, and 126 revascularization procedures. In the univariate analysis, dipyridamole resulted in higher chi 2 values than did exercise stress testing. A Cox forward stepwise survival analysis identified the dipyridamole time as the most powerful prognostic predictor of death (chi 2 = 19.4, P < .0001) of all invasive and noninvasive parameters. The dipyridamole time also provided independent and additional prognostic information when it was adjusted for age, diabetes, resting ECG, and exercise stress test according to a modified, interactive stepwise procedure. This is true when death only, death and myocardial infarction, and death, myocardial infarction, and revascularization procedures were considered end points. CONCLUSIONS In patients with no previous myocardial infarction and good resting left ventricular function, compared with exercise ECG, dipyridamole echocardiography has a similar sensitivity and a higher specificity for the noninvasive detection of angiographically assessed coronary artery disease. Dipyridamole echocardiography also provides information in addition to that provided by exercise ECG for predicting death, infarction, and all events when the presence as well as the timing, severity, and extension of dipyridamole-induced wall motion abnormalities are considered.

Coronary angiography was performed during 34 angina attacks in thirty patients admitted because of recurrent angina at rest. Nineteen (seventeen with S-T segment elevation and two S-T depression) had angiograms during a spontaneous attack, eleven (nine with S-T elevation and two with S-T depression) during an attack induced by intravenous ergonovine maleate. Control coronary angiograms showed a wide range of atherosclerotic obstruction, from normal vessels to severe triple-vessel disease. During the anginal attack, all patients with S-T segment elevation had vasospasm localised to one of the major branches, often resulting in complete occlusion. Attacks with S-T segment depression were seen only in patients with double or triple vessel disease, and here the vasospasm generally affected coronary branches without causing complete occlusion. When appropriately searched for, vasospastic angina seems to be common.

Twelve patients were studied who had frequent transient ischemic episodes at rest with a variable degree of coronary atherosclerosis and vasospastic origin of angina as evidenced by good exercise tolerance and results of thallium-201 scintigraphy during angina at rest, ergonovine maleate provocative test and coronary angiography. With the aim of keeping a constant blood drug level, the trial consisted of a continuous intravenous infusion of isosorbide dinitrate (1.25 to 5.0 mg/hour) during two periods (T 1 and T 2 ) of 24 hours (four patients) or 12 hours (eight patients) alternating with two equal periods (P 1 and P 2 ) of infusion of saline solution with a double crossover design (T 1 , P 1 , T 2 and P 2 ). Continuous electrocardiographic monitoring revealed that the total number of transient ischemic attacks at rest characterized by S-T segment elevation (four patients), S-T depression (two patients) and either S-T depression or elevation (six patients), with or without pain, was 100, 104 and 91, respectively, during the introductory control period and during P 1 and P 2 , but was reduced to 13 and 20, respectively, during periods T 1 and T 2 ( P = 0.002). Transient ischemic attacks at rest were completely prevented during both T 1 and T 2 in four patients and during T 1 or T 2 in three patients, and were not abolished but significantly reduced in T 1 and T 2 in the other five patients. The reduction in ischemic attacks was similar for episodes characterized by S-T segment elevation or depression and with or without pain. Side effects were negligible. Therefore, infusion of isosorbide dinitrate appears to be a very effective treatment for patients with vasospastic angina at rest.

From January 1970 to June 1985, transient electrocardiographic changes at rest were documented in 652 patients admitted to our coronary care unit. Patients were stratified according to the type of electrocardiographic alteration at rest: 295 had ST-segment elevation (group 1), 106 T-wave changes (group 2) and 251 ST-segment depression (group 3). Patients in group 3, compared with groups 1 and 2, were more likely to have symptoms of coronary artery disease dating back many years (p less than 0.01 and p less than 0.01, respectively), a previous myocardial infarction (p less than 0.05 and difference not significant), a positive exercise test (p less than 0.01 and p less than 0.01), transient ST-T changes occurring in a higher number of electrocardiographic leads (p less than 0.01 and p less than 0.01), multivessel disease (p less than 0.001 and p less than 0.01) and poor ventricular function (p less than 0.01 and p less than 0.05). Despite these differences, the occurrence of acute myocardial infarction and cardiac death during hospitalization was much more frequent in group 1 compared with groups 2 (p less than 0.02) and 3 (p less than 0.05). However, death occurred in those patients who had poor ventricular function and severe atherosclerosis. A greater susceptibility of group 1 patients to severe vasoconstriction documented by the ergonovine test and by the occurrence of spontaneous spasm seems to account for different in-hospital outcome.

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.

The purpose of this study was to evaluate the prognostic usefulness of basal electrocardiogram and exercise stress test in 374 patients with unstable angina submitted to coronary angiography during the same hospitalization period. After stabilization of symptoms by medical therapy, patients were subdivided into four groups according to the ECG and stress test: Group 1 (54 patients with normal ECG and exercise stress test negative for ischaemia); Group 2 (86 patients with normal ECG and exercise stress test positive for ischaemia); Group 3 (59 patients with abnormal ECG and exercise stress test negative for ischaemia); Group 4 (175 patients with abnormal ECG and exercise stress test positive for ischaemia). The severity of coronary atherosclerosis and impairment of left ventricular function increased progressively from Group 1 to 4, although differences in ventricular function were not significant between Groups 2 and 3. When discharged, patients were treated with verapamil and nitrates and followed for a period ranging from 1 to 8 years; during follow-up, only one patient of Group 1 underwent coronary bypass surgery, compared to 22, 7 and 46 patients in Groups 2, 3 and 4, respectively. The eight-year survival rate in the four groups (1-4) was 100%, 97%, 88% and 70%, respectively. Statistically significant differences were observed between Groups 1 and 3, 1 and 4, 2 and 4, and 3 and 4. Thus, the ECG and exercise stress test allow a population of patients with unstable angina to be selected (Group 1), having excellent long-term prognosis. These patients could avoid angiography, thereby reducing hospital costs, without compromising their health.

From January 1970 to December 1977, transient reversible episodes of S-T segment elevation were documented in 138 patients (80 with angina only at rest, 58 with angina both on exertion and at rest). Electrocardiographic monitoring in 33 patients with hemodynamic monitoring revealed that (1) during 6,009 transient episodes of myocardial ischemia, pain was always a late phenomenon and, in some patients, often did not occur; (2) during such transient episodes, ST-T wave behavior was often variable in the same patient with alternation of elevation, depression or only T wave changes with or without pain; (3) independent of the direction of the S-T segment and T wave changes, the episodes were never preceded by an increase of the hemodynamic determinants of myocardial demand but were associated with obvious impairment of left ventricular function. Thallium scintigraphy in 32 patients revealed a regional massive and localized reduction of myocardial perfusion during S-T segment elevation and pseudonormalization of T waves. During S-T segment depression the reduction of thallium uptake was diffuse with fuzzy limits. Coronary angiography revealed no significant stenosis in 8 patients and single, double and triple vessel disease in 38, 34 and 26 patients, respectively. Angiography in all 37 patients studied during angina revealed a severe coronary vasospasm involving vessels with extremely variable extent of atherosclerosis. Severe arrhythmias were recorded in 27 patients, and a myocardial infarction occurred in 28. A total of five patients died within 1 month of hospital admission. Thus, variable intensity and extension of coronary vasospasm and the presence of collateral vessels may result in different degrees of ischemia and various electrocardiographic patterns with or without anginal pain. Vasospastic angina can occur in the presence of extremely variable degrees of coronary atherosclerosis and in any phase of ischemie heart disease. It may evolve into acute myocardial infarction and sudden death: Variant angina appears to be only its most striking electrocardiographic manifestation. When vasospastic angina is appropriately searched for, its incidence rate appears to be high.

A patient suffering from an acute myocardial infarction presented on the seventh and eighth days of hospitalization recurrent episodes of ventricular fibrillation refractory to antiarrhythmic treatment. The life-threatening ventricular fibrillation was suppressed by percutaneous pharmacological block of the left stellate ganglion.

The role of coronary arterial vasospasm in the pathogenesis of ischemic heart disease is reviewed on the basis of investigations carried out in our laboratory. Patients were selected because they had angina either at rest or both at rest and during exercise. With continuous hemodynamic and electrocardiographic monitoring of these patients, as well as thallium-201 scintigraphy and coronary arteriography during ischemic episodes, we were able to demonstrate a vasospastic origin for the attacks. During anginal episodes, electrocardiographic changes were variable, with S-T segment elevation, S-T segment depression, a rise in T wave potential and pseudonormalization of inverted T waves corresponding to various distributions of myocardial ischemia in different patients and even in the same patient at different times. Increases in hemodynamic variables that control myocardial oxygen consumption never preceded the onset of ischemic episodes, which challenges the theory that the limitation of a possible increase in flow caused by critical organic stenosis is the only cause of myocardial ischemia. In some patients in whom myocardial infarction developed, the lesion was always found in the same area in which the vasospastic phenomena had been seen angiographically. Vasospasm led to serious arrhythmias in some patients. We therefore believe that independent of atherosclerosis or superimposed on it, vasospasm plays an important role in producing myocardial ischemia—angina, myocardial infarction and possibly sudden death. Elucidation of its mechanisms will lead to more appropriate therapy.

In hypertensive patients, the exercise-electrocardiography test shows limited feasibility and diagnostic accuracy for the noninvasive detection of coronary artery disease (CAD). Recently, the dipyridamole-echocardiograpy test (2-dimensional echo monitoring with a dipyridamole infusion of up to 0.84 mg/kg over 10 min) has been proposed as an exercise independent method for the diagnosis of CAD. In order to establish the relative diagnostic usefulness of the exercise-electrocardiography test (EET) and the ipyridamole-echocardiography test (DET) in the detection of CAD, the 2 tests were performed consecutively in 114 inpatients with a chest-pain syndrome and essential hypertension. Forty patients had previous myocardial infarction. Criteria of positivity were: for EET, a horizontal or downsloping ST segment shift > 0.1 mV; and for DET, a transient dyssynergy of contraction.

In previous studies we demonstrated that variant angina could not be attributed to increased myocardial demands. In order to investigate whether a reduction of regional myocardial blood supply could be responsible for these ischemic episodes, we studied regional myocardial perfusion in six patients admitted to our coronary care unit. Myocardial scintigrams, obtained 5-7 min following i.v. injection of 1 mCi of thallium-201, performed during an episode of ST-segment elevation, showed transmural deficits of tracer uptake in the heart wall corresponding to the leads showing ST-segment elevation. These regional deficits ahd disappeared by 2 hours because of late uptake in previously ischemic myocardium. One week later, following injections performed in the absence of acute ischemia, no deficit was apparent. Tracer uptake in ischemic areas was 60% to 85% of that observed a week later. After adjusting for thallium-201 kinetics and counting geometry promblems., these scintigrams actually represent large underestimations of actual flow reduction. Thus variant angina appears to be caused by massive transmural reduction of myocardial blood supply.

A medical approach to treatment was adopted in 652 patients with documented myocardial ischemia at rest during both the acute and fellow-up phases. No patient underwent coronary revascularization during hospitalization and only 86 patients (13%) underwent coronary bypass surgery within 8 months from discharge. During hospitalization 13 patients died. In the remaining group (639 patients), the likelihood of death in the 10-year period after discharge was 28% for all patients and 20% for cardiac causes only. A series of factors studied during the acute stage were assessed in an effort to predict long-term outcome. The following noninvasive characteristics, listed in decreasing order of statistical significance, were found to be significant univariate predictors of survival: abnormal basal electrocardiogram, duration of coronary artery disease, previous myocardial infarction, pattern of STT changes during episodes of ischemia at rest, age and systemic hypertension. The average annual mortality rate for patients with T-wave changes, ST-segment elevation and ST-segment depression was 0.9, 1.8 and 3%, respectively. The Cox survival analysis identified abnormal basal electrocardiogram, duration of coronary artery disease and pattern of ST-T changes as significant, independent predictors of death. When invasive characteristics were entered in the model, number of ≥50% narrowed coronary arteries, left ventricular ejection fraction, abnormal basal electrocardiogram and smoking habit were found to be independent and additive prognostic variables. Thus, long-term prognosis of patients with ischemia at rest is related to the severity of anatomic impairment, independent of the pattern of ST-T changes observed during the acute phase. However, noninvasive features can also be used to assess prognosis in ischemia at rest and to select high-risk populations.

Coronary vasospasm appears to be “a proved hypothesis for ‘variant’ angina„ [1], However, “variant” angina appears to be only one extreme of a continuous spectrum of vasospastic acute myocardial ischemia [2].

Sudden coronary death is a syndrome caused by different mechanisms, all of which should be separately considered with respect to preventive measures. Ventricular fibrillation, tachycardia, and complete atrioventricular block were repeatedly observed during ischemic episodes caused by spasm in both the presence and absence of anginal pain. Spasm is, therefore, a potential cause of sudden coronary death. In "variant" angina, which is a reasonably reliable indicator of coronary spasm, arrhythmias occur in about 25% of patients and tend to recur in the same patient. The severity of coronary atherosclerosis in patients who develop severe arrhythmias is quite variable and not dissimilar from patient who do not. Mortality is considerably higher in patients with severe disease, but fibrillation and death can occur also in patients with angiographically normal arteries. In these patients acute and long-term treatment with nitrates and slow channel blockers appears to give remarkable results. Prevention of arrhythmias in patients in whom arrhythmias are secondary to acute ischemic episodes caused by vasospasm should be attempted by preventing vasospasm.

One hundred thirty-eight patients with “variant angina” were followed up for periods of 2 to 8 years. All patients had a history of angina at rest, and 42 percent also had exertional angina. Normal coronary arteries were found in 9 of the 107 patients who underwent coronary arteriography; the remainder had stenosis greater than 50 percent in diameter of at least one major vessel. Coronary vasospasm was demonstrated in all 37 patients studied with coronary arteriography during angina at rest. Twenty-eight patients had acute myocardial infarction and five patients died within 1 month of admission to hospital. Of the 133 surviving patients, 120 were treated medically and 13 underwent coronary arterial surgery. In the medically treated group, only seven patients died and only four had acute myocardial infarction during the remainder of the follow-up period. Symptoms became less frequent and less severe; approximately 50 percent of the patients remained completely asymptomatic for at least 12 months by the end of the 4th year. Death, acute myocardial infarction and persistence of symptoms were more frequent in those patients with more severe coronary atherosclerotic disease although, even in this group, the overall incidence of death and acute myocardial infarction was small. It is concluded that the prognosis of patients with “variant” angina receiving appropriate medical therapy is reasonably good after the acute phase, even in the presence of severe coronary atherosclerosis.