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Background: Evaluation of coronary flow velocity reserve (CFVR) is the physiological approach to assess the severity of coronary stenosis and microvascular dysfunction. Impaired CFVR occurs frequently in women with suspected or known coronary artery disease. The aim of this study was to assess the role of CFVR to predict long-term cardiovascular event rate in women with unstable angina (UA) without obstructive coronary artery stenosis., Methods: CFVR in left anterior descending coronary artery was assessed by adenosine transthoracic echocardiograhy in 161 women admitted at our Department with UA and without obstructive coronary artery disease., Results: During a mean FU of 32.5 ± 19.6 months, 53 cardiac events occurred: 6 nonfatal acute myocardial infarction, 22 UA, 7 coronary revascularization by percutaneous transluminal coronary angioplasty, 1 coronary bypass surgery, 3 ischemic stroke, and 8 episodes of congestive heart failure with preserved ejection fraction and 6 cardiac deaths. Using a ROC curve analysis, CFVR 2.14 was the best predictor of cardiac events and was considered as abnormal CFVR. Abnormal CFVR was associated with lower cardiac event-free survival (30 vs 80%, p < 0.0001). During FU, 70% of women with reduced CFVR had cardiac events whereas only 20% with normal CFVR (p = 0.0001). At multivariate Cox analysis, smoke habitus (p = 0.003), metabolic syndrome (p = 0.01), and CFVR (p < 0.0001) were significantly associated with cardiac events at FU., Conclusion: Noninvasive CFVR provides an independent predictor of cardiovascular prognosis information in women with UA without obstructive coronary artery disease whereas, impaired CFVR seems to be associated with higher CV events at FU., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Few studies have examined the effect of transmurality of myocardial necrosis on coronary microcirculation. The aim of this study was to examine the influence of cardiac magnetic resonance-derived (GE-MRI) structural determinants of coronary flow reserve (CFR) after anterior myocardial infarction (STEMI), and their predictive value on regional functional recovery., Methods: Noninvasive CFR and GE-MRI were studied in 37 anterior STEMI patients after primary coronary angioplasty. The wall motion score index in the left descending anterior coronary artery territory (A-WMSI) was calculated at admission and follow-up (FU). Recovery of regional left ventricular (LV) function was defined as the difference in A-WMSI at admission and FU. The necrosis score index (NSI) and transmurality score index (TSI) by GE-MRI were calculated in the risk area. Baseline (BMR) and hyperemic (HMR) microvascular resistance, arteriolar resistance index (ARI), and coronary resistance reserve (CRR) were calculated at the Doppler echocardiography., Results: Bivariate analysis indicated that the CPK and troponin I peak, heart rate, NSI, TSI, BMR, the ARI, and CRR were related to CFR. Multivariable analysis revealed that TSI was the only independent determinant of CFR. The CFR value of >2.27, identified as optimal by ROC analysis, was 77% specific and 73% sensitive with accuracy of 76% in identifying patients with functional recovery., Conclusions: Preservation of microvascular function after AMI is related to the extent of transmurality of myocardial necrosis, is an important factor influencing regional LV recovery, and can be monitored by noninvasive CFR., (© 2019 Wiley Periodicals, Inc.)

Background: Microvascular coronary impairment, defined as reduced coronary flow reserve, represents the predominant etiologic mechanism of ischemia in women with chest pain and no obstructive coronary artery disease. Transthoracic echocardiography (TTE) is a noninvasive method for assessing coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD). The purpose of this investigation was to define the safety profile, feasibility, adverse events, and rate of complications of the test in women with suspected CAD., Methods: We evaluated CFVR in LAD with TTE during adenosine infusion in 1455 women aged 66.4±11.9 years., Results: A complete CFVR study was achieved in 1429 pts (feasibility 98.2%), the test being performed also in the early phase of acute coronary syndrome and on obese patients. Minor symptoms or adverse effects occurred in 43.7% of patients not requiring test termination: hyperpnea (16.7%), flushing (9.4%), atypical chest pain (9.9%), headache (6.6%), minor arrhythmias (2.9%), chest pain with EKG changes (1.5%) were the symptoms reported. No major complications were observed., Conclusions: Noninvasive assessment of CFVR in LAD by TTE is a very feasible method with very low incidence of adverse events and complications in women with suspected or known CAD. It is safe and can be used when evaluating female patients with atherosclerotic LAD disease or with coronary microvascular impairment., (© 2017, Wiley Periodicals, Inc.)

Aims: The aim of this study is to investigate the long-term impact of a prehospital ECG programme on treatment times for patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI)., Methods: From January 2008 to December 2012, 213 STEMI patients transported by the Emergency Medical System (EMS) underwent primary PCI in our Hospital. The protocol included ECG tele-transmission, early activation of the cath lab and direct routing of the patient for primary PCI. Fifty-four patients referred by EMS in 2007, when ECG tele-transmission was unavailable, were used as controls. First diagnostic ECG-to-balloon time, door-to-balloon time and total ischemic time were collected for all patients., Results: First diagnostic ECG-to-balloon time decreased from 125.5 min in 2007 to 104 min in the first year after implementation of the STEMI programme (2008). Successively, it declined to 81 min by the end of the study period (2012) (P < 0.0001). Door-to-balloon time decreased notably from 92.5 min in 2007 to 40.5 min by the end of the study period (p < 0.0001). Total ischemic time fell from 200 min in 2007 to 170 min in 2008 and it further declined to 163.5 min in 2012 (p < 0.042)., Conclusions: We report progressive improvements in times to treatment over a 5-year period in a STEMI program for patients referred by the EMS. The importance of data collection and monitoring is highlighted by our results.

Aim: The aim of this study was to investigate the relationship between admission plasma glucose levels and abnormal glucose metabolism in patients with acute myocardial infarction (AMI) without a previous diagnosis of diabetes mellitus., Methods: A total of 285 nondiabetic patients admitted with AMI were screened for glucometabolic disorders by using fasting glucose measurements during hospital stay or an oral glucose tolerance test on discharge. Patients diagnosed as having diabetes mellitus were followed-up for a mean of 60 ± 33 months in order to confirm the diagnosis., Results: There was a graded relationship between admission glucose levels and the prevalence of newly detected diabetes mellitus (group 1, <140 mg/dl: 12%; group 2, ≥140 < 200 mg/dl: 40%; group 3, ≥200 mg/dl: 70.3%; P < 0.0001). The admission glucose level of at least 144 mg/dl was the best predictor of newly detected diabetes mellitus during hospitalization (area under the curve 0.78, P = 0.0001). In multivariable analysis, patients with admission hyperglycemia had greater odds of having newly detected diabetes mellitus (odds ratio 6.6, 95% confidence interval 2.7-16.3, P = 0.0001). Diabetes mellitus was confirmed in the long-term follow-up in 78% of patients diagnosed as having diabetes mellitus during hospitalization., Conclusion: Our finding suggests a relationship between admission glucose and previously undetected diabetes mellitus in nondiabetic patients presenting AMI. Acute hyperglycemia may help to identify high-risk patients for diabetes mellitus, who should be screened initially for glucometabolic disorders, then closely monitored and appropriately treated to improve outcome.

Introduction: Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome., Methods: Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7-±3.5-year follow-up., Results: Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r=-0.57, P<0.0001) was observed; in addition, CFR was significantly reduced (2.21±0.38) in patients with WMA as compared to those without (2.94±0.60) (P<0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7-±3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests., Conclusions: A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases.

Background: Coronary restenosis is the most important clinical limitation after percutaneous coronary intervention (PCI), and coronary flow reserve (CFR) is reduced in the presence of significant coronary stenosis. This study evaluated whether detection of early reduction of Doppler echocardiographically derived CFR in the left anterior descending coronary artery can identify patients at high risk for developing restenosis after successful PCI., Methods: Doppler echocardiographically derived CFR was studied in 124 consecutive patients at 1-month and 6-month follow-up after PCI in the left anterior descending coronary artery, together with coronary angiography., Results: Restenosis was detected in 39 angiographic examinations (group A) and no coronary restenosis in the remaining 85 (group B) at 6 months. At 1 month, CFR was reduced in group A compared with group B (P < .0001), and a significant reduction of CFR in group A (P < .0001) but not in group B (P = .89) was detected at 6 months. CFR ≤ 2.5 at 1 month was 67% sensitive and 87% specific for predicting significant restenosis, with positive and negative predictive values of 67% and 87%, respectively., Conclusions: CFR ≤ 2.5 detected 1 month after PCI in the left anterior descending coronary artery has the potential to identify patients at higher risk for developing coronary restenosis and indicates the need for close clinical follow-up., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: The chronic consumption of androgenic anabolic steroids (AAS) has shown to cause subclinical impairment of myocardial function. Pulsed-wave Doppler tissue imaging (PWDTI) detects early regional alterations of ventricular function, whereas integrated backscatter cyclic variations (IBScv) are tightly related to the contractile efficiency of the left ventricular wall. The aim of this study was to identify the effects of chronic AAS misuse on myocardial function using both PWDTI and IBScv., Methods: Twenty-eight male bodybuilders (11 AAS users, 17 AAS nonusers) and 20 healthy sedentary subjects (controls), matched according to age, were studied. To assess left ventricular function, each subject underwent standard Doppler echocardiography, PWDTI, and IBScv analyses., Results: Left ventricular mass was significantly higher in AAS users than in AAS nonusers and controls. Global systolic function (assessed by determining the ejection fraction) was similar in all subjects, but isovolumetric relaxation time was significantly higher in AAS users than in controls. On PWDTI analysis, AAS users showed regional systolic and diastolic dysfunction (evaluated by measuring s', e', and a') not detectable in the other two groups. IBScv identified regional systolic impairment only in AAS users at the level of the left ventricular inferior wall., Conclusions: The present study confirms that in AAS users, PWDTI and IBScv are effective and reliable noninvasive diagnostic tools for detecting early abnormalities of the systolic and diastolic longitudinal myocardial function, probably related to an increase in myocardial collagen content, interpretable as a repair process against the direct cellular injury produced by AAS., (2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Our aim in this part of the Sardinian Hypertensive Adolescents Research Programme, also known as the SHARP study, was to use longitudinal screening over a period of 3 years to search for any relationship between hypertension and excessive weight in a number of Southern Italian students. We also sought to establish if this correlation can change according to the criterion used to define children considered to be overweight.We studied 839 children, of whom 52.6% were male, defining hypertension as an average blood pressure exceeding the 95th percentile according to previous Italian reference tables. We defined those overweight using different criteria, first those with a body mass index exceeding 25 kilograms per square metres, second those with the index exceeding the 85th percentile, third using the references established by Rolland-Cachera, and fourth according to the relative body weight. The different methods used in defining overweight produced very different estimates, ranging from 8.9% to 26.4%. Our novel findings were that systolic hypertension was present in all children deemed overweight using any of the criteria, but only use of the second and third criteria produced results related significantly to both systolic and diastolic hypertension. In short, excessive weight is strongly associated with systolic hypertension in adolescence. Definition of those being overweight on the basis of a body mass index exceeding the 85th percentile, or using the references established by Rolland-Cachera, proved to be best related with both systolic and diastolic hypertension.

The Sardinian Hypertensive Adolescents Research Programme Study, which for the sake of simplicity we will describe as SHARP, was aimed at detecting the prevalence of hypertension in a number of Southern Italian students, using a process of longitudinal screening lasting 3 years, hoping to answer the question whether it is better to use tables charting values established in the United States of America, or to use charts specific for the Italian population.In all, we studied 839 children, of whom 52.6% were male. We defined hypertension as the average blood pressure exceeding the 95th percentile according to previous tables prepared by the United States Task Force, and previous Italian references. Use of the American tables identified very high proportions of hypertensive subjects if compared with the distribution curves from our own study (p less than 0.00001), albeit that our findings correlated well with previous Italian charts as reference (no statistical significance).In short, notwithstanding a little difference in millimetres of mercury about the same percentiles, the tables prepared in the United States of America overestimate the prevalence of hypertension, specific Italian material being more suitable for our needs. Our study emphasises the need to integrate these standards with more up-to-date and representative reports on Italian children, as is done periodically in the United States of America. Even using the Italian specific charts, nonetheless, hypertension was more common in Sardinian children than would be expected from international studies, with one-tenth of the sample being hypertensive.

Background: Determination of coronary flow reserve (CFR) is increasingly being used in cardiac allograft vasculopathy (CAV). We aimed to identify determinants of CFR in heart transplantation (HT)., Methods: CFR was measured by transthoracic echocardiography in 119 HT recipients (97 men, 22 women; 50 +/- 12 years of age at HT and 8 +/- 5 years post-HT). CFR was expressed as the ratio of hyperemic (adenosine infusion at a rate of 0.14 mg/kg) to basal diastolic flow velocity. Rejection scores (RS) on endomyocardial biopsy were calculated. Angiographic CAV was analyzed using a qualitative grading system. The coronary tree was divided into 17 traits and a CAV severity/diffusion index (SDI) was calculated for each patient, summing the scores assigned to all lesions., Results: Upon multivariate analysis, CFR was related to CAV (p = 0.001), interventricular septum thickness (p = 0.01), ischemic heart disease pre-HT (p = 0.02) and SDI and SDI/segment number (p < 0.0001 and p = 0.003, respectively). In patients without CAV, CFR was related only to RS for severe grades (p = 0.01)., Conclusions: Left ventricular hypertrophy, CAV and its severity/diffusion independently contribute to reduced CFR. In patients without angiographic CAV, CFR was only independently related to RS. Because a high rejection burden is associated with increased risk of CAV, CFR reduction may be an early marker of CAV. Microvascular dysfunction may contribute to the late morbidity and mortality seen in HT.

Partial anomalous pulmonary venous connection is a rare congenital heart defect and it is usually difficult to identify by transthoracic echocardiography alone. Here we report a case in a newborn, identified by echocardiographic imaging techniques with subcostal views, to detect the anomalous venous return. Our case is an uncommon one, as regards both its anatomy and early diagnosis. Surgical repair can be safely managed by means of multiple techniques with low morbidity. This correction may be associated with complications such as superior vena cava occlusion and sinus node dysfunction.

We investigated whether coronary flow reserve (CFR) can be modified by tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, in patients with documented coronary artery disease (CAD). CFR was non-invasively evaluated in 12 men with a positive history for erectile dysfunction (ED) and angiographically documented CAD, in the distal portion of the left anterior descending coronary artery, free from critical stenosis, with contrast enhanced echocardiography at time zero (T0). Then, after 20 mg tadalafil was orally administered CFR measurement was repeated after 2 h (T1) and after 24 h (T2). Doppler curves suitable for the analysis were obtained in all patients (CFR feasibility: 100%). The peak diastolic velocity after adenosine infusion increased from 71.3+/-14.3 cm/s at T0 to 82.5+/-24.0 at T1 (P=NS) and to 89.5+/-21.1 at T2 (P=0.0010). CFR after tadalafil increased significantly from 2.6+/-0.3 at T0 to 3.1+/-0.7 at T1 (P=0.0078) and a further increment was found at T2 (3.5+/-0.9; P=0.0010 vs T0). Our study shows that oral administration of tadalafil exerts a long standing, potentially beneficial effect on coronary microvasculature in patients with ED.

Background: It has been observed that in patients with ST-elevation myocardial infarction (STEMI) the presence of ST-segment depression (ST) in heterozonal electrocardiographic leads (remote STI) worsens the patient's prognosis. The aim of this study was to observe in an unselected population with a first STEMI the incidence of remote STI and the risk factors related to this condition., Methods: We evaluated retrospectively 350 patients with a first STEMI; we excluded from our analysis 139 patients because no data about their coronary anatomy was available. ST-segment depression in the heterozonal myocardium was considered significant if > 0.1 mV at 60 ms from the J point, in at least two electrocardiographic leads., Results: Patients were classified according to the presence (group 1, 117 patients) or absence (group II, 94 patients) of remote ST. The two groups did not differ for age, sex and coronary anatomy. In group I we found more heterozonal wall motion abnormalities than group II (32 vs. 18%, p = 0.018). In this group there was a higher incidence of smokers (56 vs. 33%, p = 0.025) and less patients were treated with statins when the STEMI occurred (6 vs. 14%, p = 0.047). Patients with remote ST had higher total cholesterol (214.6 +/- 48.9 vs. 192.3 +/- 29.8 mg/dl, p < 0.001) and low-density lipoprotein cholesterol (138.7 +/- 40.7 vs. 123.2 +/- 22.9 mg/dl, p < 0.0001) levels. Conclusions. In patients with STEMI the presence of remote ST is rather frequent, and seems to indicate a real heterozonal ischemia, independently of an epicardial coronary stenosis of the non-infarct-related artery. Remote ST. is associated with a higher incidence of risk factors related to microcirculatory dysfunction, such as cigarette smoking, a worse lipid profile and less protective factors, such as the use of statins prior to acute myocardial infarction.

Background: Scleroderma-related cardiac involvement primarily affects coronary microvascular structures and function. The microvasculature disorder is responsible for impairment of coronary flow velocity reserve (CFVR), which has been reported in studies of patients with systemic sclerosis (SSc). L-propionylcarnitine (L-PC) is a metabolic substance that is associated with a beneficial effect on both microcirculation and myocyte function., Objective: The objective of this study was to determine whether or not CFVR was acutely improved or restored in patients with SSc after a single administration of IV L-PC., Methods: In this pilot study, we screened volunteers with SSc who had no clinical evidence of ischemic heart disease. CFVR was determined by a blinded investigator by evaluating the left anterior descending coronary artery (LADCA) by transthoracic echocardiography during adenosine infusion (140 microg/kg x min(-1) for 5 minutes), 30 minutes before and 15 minutes after administration of L-PC (300 mg IV in 5-minute bolus)., Results: Thirty-three patients were screened for this study. Fourteen patients (mean [SD] age, 54.3 [11.2] years; mean [SD] weight, 63.8 [14.5] kg; mean [SD] height, 156.3 [8.7] cm) with SSc and no evidence of coronary heart disease were included in the study; 13 women and 1 man (4 with the diffuse cutaneous form of SSc and 10 with the limited cutaneous form). After administration of L-PC to patients with SSc, median CFVR was significantly increased from 2.60 to 3.23 (P < 0.001), whereas peak diastolic velocity in the LADCA decreased significantly at the basal evaluation (30.0 vs 26.0, P = 0.009) and significantly increased (80.0 vs 87.5, P = 0.005) during adenosine infusion. No adverse events occurred before, during, or after L-PC infusion., Conclusions: Acute administration of L-PC was associated with a short-term beneficial effect on CFVR in this pilot study of patients with SSc. These results suggest that further, randomized, controlled, double-blind evaluation of longer-term administration to patients with SSc should be considered.

Background: Pulmonary arterial hypertension (PAH) is a life-threatening and debilitating complication of several connective tissue diseases. We aimed to evaluate the effects of long-term treatment with bosentan, an oral dual endothelin ET(A)/ET(B) receptor antagonist, in a cohort of patients with PAH related to connective tissue diseases., Materials and Methods: In the present prospective, noncontrolled study, 13 patients (nine with systemic sclerosis, two with systemic lupus erythematosus, one with mixed connective tissue disease and one with overlap syndrome including scleroderma and myositis), mostly nonresponders to prostanoids therapy, were treated for 1 year with bosentan. Cardiac haemodynamics and the diagnosis of PAH were performed by Doppler ultrasound examination. Exercise capacity was assessed by 6-min walking test at baseline and at 3, 6 and 12 months of therapy., Results: During bosentan treatment, progressive improvement of exercise capacity was observed. Walk distance increased in seven patients, remained unchanged in three and slightly decreased in three patients. A progressive significant decrease of right ventricular systolic pressure was also observed, whereas pulmonary artery mean pressure remained unchanged. Adverse effects related to bosentan (elevation of hepatic aminotransferases) were noted in two patients., Conclusion: Long-term treatment with bosentan was effective in improving exercise capacity and pulmonary haemodynamics in patients with PAH related to connective tissue diseases.

Objective: To test whether preserved coronary flow reserve (CFR) two days after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction (" no-reflow" phenomenon) and is predictive of myocardial viability., Design: 24 patients with anterior AMI underwent CFR assessment in the left anterior descending coronary artery (LAD) with transthoracic echocardiography and myocardial contrast echocardiography (MCE) 48 h after primary angioplasty in the LAD (mean 4 (SD 2) and 3 (1) days, respectively). Low-dose dobutamine echocardiography was performed 6 (3) days after AMI and follow-up echocardiography at three months., Results: No-reflow extent was greater in patients with impaired CFR (< 2.5) than in those with preserved CFR (> 2.5) (55 (35)% v 11 (25)%, p < 0.001). MCE reflow was more common in patients with preserved CFR (8/12) than in those with reduced CFR (1/12, p < 0.05). Wall motion score index in the LAD territory (A-WMSI) was similar at the first echocardiography (2.14 (0.39) v 2.32 (0.47), NS), although it was better in patients with preserved CFR at dobutamine (1.38 (0.45) v 1.97 (0.67), p < 0.05) and follow-up echocardiography (1.36 (0.40) v 1.97 (0.64), p < 0.05). An inverse correlation was found between CFR and A-WMSI at dobutamine and follow-up echocardiography (r = -0.49, p = 0.016 and r = -0.55, p = 0.005) and between MCE and A-WMSI at dobutamine and follow-up echocardiography (r = -0.75, p < 0.001 and r = -0.75, p < 0.001). By multivariate analysis MCE reflow remained the only predictor of recovery at both dobutamine and follow-up echocardiography (odds ratio 1.06, 95% CI 1 to 1.1, p = 0.009)., Conclusion: CFR is inversely correlated with the extent of microvascular dysfunction at MCE two days after reperfused AMI. CFR and MCE reflow early after AMI are correlated with myocardial viability at follow up.

Background: We assessed coronary flow velocity pattern and coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) as markers of major adverse cardiac events (MACE) related to cardiac allograft vasculopathy (CAV) after heart transplantation (HT)., Methods and Results: Deceleration time of diastolic flow velocity (DDT) and CFR were measured in the left anterior descending coronary artery (LAD) by CE-TTE in 66 consecutive HT patients (follow-up 19+/-5 months). CFR was calculated as the ratio of hyperemic to basal diastolic flow velocity. Angiographies were analyzed by a qualitative grading system; CAV was defined as changes grade II or higher. MACE were cardiac death, stent implantation, and heart failure. Patients with MACE had higher CAV incidence (P=0.004) and grade (P=0.008), shorter DDT (P=0.006), and lower CFR (P=0.008). A receiver-operating characteristic-derived DDT cutpoint < or = 840 ms (area under the curve 0.793; P=0.01) was 75% specific and 86% sensitive for predicting MACE, with positive predictive value (PPV) and negative predictive value (NPV) of 33% and 97%, respectively (P=0.002). A CFR cutpoint of < or =2.6 (area under the curve 0.746; P=0.01) was 62% specific and 91% sensitive for predicting MACE (PPV =32%, NPV =97%) (P=0.001). Patients with CFR < or = 2.6 and patients with DDT < or = 840 ms had a lower survival free from MACE (P=0.006 and P=0.009, respectively). By Cox regression, only a lower CFR predicted the risk of MACE (relative risk 3.1; 95% CI, 1.26 to 7.9; P=0.01)., Conclusions: In HT patients, shorter DDT and lower CFR by CE-TTE are reliable markers for CAV-related MACE. CFR is the main independent predictor of MACE.

Noninvasive tests have proven unsatisfactory in cardiac allograft vasculopathy (CAV) diagnosis. We assessed coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) in heart transplantation (HT). CFR was assessed in the left anterior descending coronary artery in 73 HT recipients (59 male, aged 50+/-12 years at HT), at 8+/-4.5 years post-HT. CFR measurements were taken blindly from coronary angiographies. CFR cut points were the standard value of

Objective: To investigate whether coronary flow reserve (CFR), measured by a new non-invasive method, is impaired early in patients with systemic sclerosis (SSc) and whether CFR impairment correlates with clinical or functional measures, or both., Methods: 27 patients with SSc without clinical evidence of ischaemic heart disease and 23 control group subjects matched for age and sex were studied. CFR was evaluated in the left anterior descending coronary artery (LAD) with a new non-invasive method: contrast (Levovist) enhanced transthoracic Doppler during adenosine infusion. The pulsed wave Doppler examination of blood flow velocity was recorded in the LAD at rest and after maximum vasodilatation by adenosine infusion., Results: In patients with SSc, without clinical evidence of ischaemic heart disease, CFR was impaired (p=0.0001). 14/27 patients with SSc had severe reduction of the CFR (< or =2.5) compared with controls (p=0.002). A non-significant trend between mean CFR and the severity and duration of the disease was also seen., Conclusions: CFR is often reduced in patients with SSc, suggesting early preclinical cardiac involvement in SSc. This impairment in coronary microvasculature is detectable by a non-invasive echocardiographic method and in this study was more common in the diffuse form of SSc.

Background: After acute myocardial infarction, the presence of ischemic preconditioning as a result of preinfarction angina has a protective role, limiting necrosis extent and guaranteeing greater myocardial functional recovery. The relationship between preinfarction angina, microvascular reflow, and myocardial function is poorly known. We hypothesized that after acute myocardial infarction patients with preinfarction angina have both microvascular integrity and myocardial function preservation., Methods and Results: In 51 patients with a first acute myocardial infarction, we noninvasively assessed microvascular perfusion and coronary flow reserve with intravenous myocardial contrast echocardiography and investigated myocardial contractile recovery with low-dose dobutamine and 90-day follow-up echocardiography. Typical angina was present in 25 patients and absent in 26 patients during the 7 days preceding the myocardial infarction. Compared with those patients without preinfarction angina, patients with preinfarction angina showed a greater microvascular reflow extent and coronary flow reserve (respectively, 25.2% +/- 22.8% vs 48.3% +/- 23.3%, P <.05, and 3.44 +/- 0.75 vs 1.95 +/- 0.67, P <.0001), a better regional myocardial function, as expressed with wall motion score index in the risk area at dobutamine (1.67 +/- 0.61 vs 2.10 +/- 0.43, P <.005) and at follow-up (1.72 +/- 0.56 vs 2.22 +/- 0.40, P <.0001) echocardiogram, despite being similar in the first echocardiogram (2.60 +/- 0.28 vs 2.63 +/- 0.28, P = not significant), and significantly less pronounced left ventricular dilation at follow-up., Conclusion: Presence of preinfarction angina, because of the preconditioning effect, reduces myocardial damage and favors myocardial viability, limiting left ventricular remodeling. This beneficial effect seems to be at least partly mediated by the more preserved microvascular integrity and functional vasodilation after acute myocardial infarction.

Objectives: This study sought to evaluate the diagnostic potential of contrast-enhanced transthoracic echocardiography (CE-TTE) during adenosine infusion, a noninvasive method for evaluating coronary flow reserve (CFR), in detecting restenosis after successful percutaneous transluminal coronary angioplasty (PTCA)., Background: Restenosis is the most important limitation of PTCA, and CFR can be impaired in patients with angiographically documented significant coronary stenosis., Methods: We performed 6 +/- 2 months of follow-up of 53 patients after successful elective PTCA in the left anterior descending coronary artery (LAD). Coronary angiography was performed at the end of the planned follow-up period or even before, if clinically indicated. Thus, of the 53 patients, a total of 63 angiographic studies were performed; CE-TTE assessment of CFR was achieved before each of the 63 angiographic studies., Results: Coronary angiography revealed the presence of restenosis (defined as >50% stenosis at a previous PTCA site) in 32 angiographic examinations (group A) and no coronary restenosis in the remaining 31 examinations (group B). Coronary flow reserve was significantly reduced in group A compared with group B (1.65 +/- 0.5 vs. 3.17 +/- 0.8, p < or = 0.001). A noninvasive CFR value < or = 2 was 93% specific and 78% sensitive for detecting significant restenosis, with positive and negative diagnostic accuracies of 92% and 80%, respectively., Conclusions: Noninvasive CFR assessment by CE-TTE is an accurate method of monitoring significant restenosis in the LAD when following up patients submitted to elective PTCA.

Background: After acute myocardial infarction the preservation of the microvasculature is a pre-requisite for myocardial viability, limited ventricular remodeling and a better prognosis. Intracoronary myocardial contrast echocardiography after acute myocardial infarction can detect the extent of microvascular damage. We hypothesized that intravenous myocardial contrast echocardiography after acute myocardial infarction treated with primary coronary angioplasty can predict the contractile reserve at low-dose dobutamine echocardiography, myocardial functional recovery and left ventricular remodeling., Methods: We studied 37 patients with a first acute myocardial infarction and submitted to primary coronary angioplasty. All patients underwent echocardiography on the day they had the acute myocardial infarction, intravenous myocardial contrast echocardiography with power Doppler imaging 2.9 +/- 0.5 days later and dobutamine echocardiography 3.7 +/- 1.2 days after the acute myocardial infarction. In all cases, an echocardiography was performed at 3 months of follow-up., Results: At intravenous myocardial contrast echocardiography, 25 patients showed contrast enhancement (reflow) and 12 a sizeable contrast defect (no-reflow). Reflow patients were found to have a regional wall motion score index similar to that of the no-reflow patients on the first day echocardiogram (2.6 +/- 0.4 vs 2.8 +/- 0.2, p = NS), but this parameter was smaller than that of the no-reflow patients at dobutamine echocardiography (1.5 +/- 0.4 vs 2.6 +/- 0.2, p < 0.0001) and at follow-up echocardiography (1.5 +/- 0.5 vs 2.6 +/- 0.2, p < 0.0001). The sensitivity and specificity of intravenous myocardial contrast echocardiography in identifying myocardial functional recovery at follow-up were 80 and 64%, while the sensitivity and specificity of dobutamine echocardiography were 85 and 76%. In no-reflow patients the left ventricular volumes increased from the acute to the chronic phase (end-diastolic volume from 71.9 +/- 14.1 to 100.9 +/- 40.6 ml/m2, p < 0.0001, +28%; end-systolic volume from 43.1 +/- 10.1 to 61.1 +/- 30.1 ml/m2, p < 0.0001, +29%), while they remained constant in reflow patients (end-diastolic volume from 71.8 +/- 20.1 to 71.1 +/- 15.4 ml/m2, p = NS, -1%; and end-systolic volume from 39.9 +/- 11.9 to 36.3 +/- 12.8 ml/m2, p = NS, -8%)., Conclusions: Intravenous myocardial contrast echocardiography is capable of identifying patients with a post-infarction contractile reserve and myocardial functional recovery; it also allows the early identification of patients prone to late left ventricular dilation, thus permitting a more aggressive diagnostic and therapeutic strategy.

The authors' aim is to outline some of the main medico-legal problems in cardiology, especially those regarding the premature hospital discharge of patients with undefined chest pain and/or with acute myocardial infarction. After a brief overview on the etiology and clinical definition of chest pain and myocardial infarction, premature hospital discharge is defined and the incidental medico-legal risks that physicians operating in such situations are exposed to are pointed out. Next, the profiles regarding both the positive and negative views of professional medical responsibility are described. In the negative frame, the authors outline the most frequent civil and penal aspects of the unpremeditated responsibility. Then the physician's error, in both qualitative (generic or specific guilt) and quantitative (degree) terms, is considered; particularly, negligence, imprudence and inexperience, as qualitatively accepted meanings of generic guilt, are dealt with by adopting illustrative cases settled in the light of the right legal interpretation. The phases of the diagnostic or prognostic error are evaluated, and clinical protocols, as a reference parameter for the identification of error, are considered. Lastly, the problem of causality, essential condition for the judgment about the professional responsibility, and the problem of the patient's consent, including an evaluation of the legal capability or incapability about the declaration of consent, are examined closely.

Objectives: We tested the hypothesis that coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD) as assessed by a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) is in agreement with CFR measurements assessed by intracoronary Doppler flow wire., Background: Contrast-enhanced transthoracic second harmonic echo Doppler is a novel noninvasive method to detect blood flow velocity and reserve in the LAD. However, it has not yet been validated versus a gold-standard method., Methods: Twenty-five patients undergoing CFR assessment in the LAD by Doppler flow wire were also evaluated by contrast-enhanced transthoracic Doppler to record blood flow in the distal LAD at rest and during hyperemia obtained by adenosine i.v. infusion. In five patients CFR was evaluated twice (before and after angioplasty)., Results: As a result of the combined use of i.v. contrast and second harmonic Doppler technology, feasibility in assessing coronary flow reserve equaled 100%. The agreement between the two methods was high. In fact, in all but five patients the maximum difference between the two CFR measurements was 0.38. Overall, the prediction (95%) interval of individual differences was -0.69 to +0.72. Reproducibility of CFR measurements was also high. The limits of the agreement (95%) between the two measurements were -0.32 to +0.32., Conclusions: Coronary flow reserve in the LAD as assessed by contrast-enhanced transthoracic echo Doppler along with harmonic mode concurs very closely with Doppler flow wire CFR measurements. This new noninvasive method allows feasible, reliable and reproducible assessment of CFR in the LAD.