Giuliana Menegatti

Evidence of parasympathetic impairment in some patients with cardiac syndrome X.

OBJECTIVES Cardiac syndrome X (SX) is a clinical condition characterised by angina, positive exercise stress test and negative coronary angiography; it has often been attributed to sympathetic hyperactivity. Here we tested the hypothesis that a parasympathetic, rather than a sympathetic, dysfunction could be the cause of the autonomic imbalance observed in SX. METHODS In 20 subjects with diagnosed SX and in 12 age-matched controls, we studied autonomic function by performing spectral analysis of RR interval and finger arterial pressure (SAP), in supine position and during head-up tilting. We also carried out a set of tests of parasympathetic function. RESULTS The group of SX patients did not differ significantly from control subjects in any of the variables tested. In a subgroup of 13 SX, however, tilting increased the low-frequency power of SAP, but did not induce the expected increase in low-frequency and decrease in high-frequency power of RR. These patients, in supine position, had significantly lower sinus arrhythmia and a higher ratio of low to high frequency of RR, in comparison with control subjects. We interpreted these differences as signs of reduced parasympathetic, but essentially normal sympathetic, activity. The parasympathetic tests confirmed vagal impairment in the same SX subjects. On the other hand, all the tests indicated normal parasympathetic functions in the control subjects and in those SX patients who displayed the expected spectral changes in tilting. CONCLUSIONS In about two thirds of the patients with SX, the pathophysiological mechanism causing the symptoms could be related to the reduced parasympathetic tone, rather than to an augmented sympathetic activity.

Coronary vasoconstriction in response to acetylcholine after balloon angioplasty: possible role of endothelial dysfunction

BackgroundAbnormal endothelium-dependent vasomotion has frequently been observed early after coronary angioplasty. The aim of this study was to investigate endothelium-mediated coronary vasomotion caused by increasing intracoronary infusions of acetylcholine into epicardial coronary arteries 3–6 months after coronary angioplasty in patients without restenosis (50% luminal diameter reduction). MethodsIntracoronary acetylcholine was infused during follow-up coronary angiography followed by an intracoronary bolus of 250 g nitroglycerin in 18 patients who had undergone successful angioplasty of 21 isolated coronary artery lesions. Using an automated edge-detection program, coronary artery measurements were performed in the proximal reference segment, in the proximal part of the angioplasty site, at the site of previous maximal stenosis, in the distal part of the angioplasty site, and in the distal reference segment. ResultsIn the segments of the coronary artery not manipulated by balloon catheter, acetylcholine did not produce significant luminal diameter changes (+2 ±23% in the proximal segment and −3±27% in the distal segment at 10-4mol/l). All the angioplasty vessel segments, excluding the proximal reference segments, showed an abnormal dose-related reactivity to the acetylcholine. Maximal vasoconstriction was observed at 10-4mol/l and was 4.9±11.1% in the proximal reference segment, 9.3±19.1% in the proximal angioplasty site (P=0.0314), 20.3±24.1% at the site of previous maximal stenosis (P= 0.0005), 10.7 ±16.8% at the distal angioplasty site (P= 0.0098), and 9.3± 14.1% in the distal reference segment (P=0.0032). The maximal response of the angioplasty site to acetylcholine and to nitroglycerin did not correlate either with the time to follow-up or with the follow-up stenosis. Nitroglycerin-induced vasodilation was significant in all segments, but was lower in the lesion-related segments. Acetylcholine evoked the same effect on both the vessels that were manipulated and those that were not. ConclusionsThree to 6 months after coronary angioplasty, endothelium-dependent vasodilation was impaired not only at the site of previous maximal stenosis, but also in segments directly injured by balloon inflation. In contrast, endothelium-independent vasodilation by nitroglycerin is maintained in all segments. These observations suggest that the endothelium is still functionally impaired in the area of balloon dilation.

Acute electrocardiographic differences between Takotsubo cardiomyopathy and anterior ST elevation myocardial infarction.

BACKGROUND The aim of this study was to compare ECG findings between anterior ST elevation myocardial infarction (STEMI) and Takotsubo cardiomyopathy (TC) in a similar sample of postmenopausal women. METHODS Between 2008 and 2011, 27 patients with TC were retrospectively enrolled and matched with 27 STEMI patients with the same age and sex taken from the prospective database of our laboratory. RESULTS The absence of abnormal Q waves, the ST depression in aVR and the lack of ST elevation in V1 were significantly associated with TC (respectively: 52% vs 18%, p=0.01; 47% vs 11%, p=0.01; 80% vs 41%, p=0.01). The combination of these ECG findings identified TC with a specificity of 95% and a positive predictive value of 85.7%. CONCLUSIONS The ECG on admission may be useful to distinguish TC from anterior STEMI. The combination of three ECG findings identifies patients with TC with high specificity and positive predictive value.

CPK and CPK-MB in the early diagnosis of acute myocardial infarction and prediction of infarcted area

This study was carried out on patients of a coronary unit to evaluate the diagnostic efficiency of total CPK and CPK-MB by using different analytical techniques: catalytic, immunoassisted, cellulose acetate electrophoresis, radioimmunoassay and immunoradiometric assay. The behaviour of the enzyme was studied in all patients with reference to the localization and extent of the infarct. In all cases a diagnostic algorithm was followed based on the combined use of CPK and its MB isoenzyme; the activity was measured twice, at three-hour intervals after admission. In this way the utilization of total CPK and MB isoenzyme allows almost complete diagnostic efficiency within the first 9 hours from onset of chest pain, together with the possibility of calculating the slope of the curve of MB isoenzyme release useful for calculating infarct size. Maximum diagnostic efficiency is also obtained in cases of small infarcts, with silent ECG, and those difficult to classify clinically.

Tpeak-to-Tend/QT is an independent predictor of early ventricular arrhythmias and arrhythmic death in anterior ST elevation myocardial infarction patients

Background: The aim of our study was to analyse the markers of transmural dispersion of ventricular repolarization, especially Tpeak-to-Tend and Tpeak-to-Tend /QT ratio, in patients with anterior ST elevation myocardial infarction on admission and to evaluate their association with in-hospital life-threatening arrhythmias and mortality. Methods and results: A total of 223 consecutive patients with anterior wall ST elevation myocardial infarction admitted to our Division of Cardiology between January 2010 and December 2012 were prospectively evaluated. A standard electrocardiogram was obtained on admission and then analysed. The primary end point was constituted by in-hospital ventricular arrhythmias and arrhythmic death. At univariate analysis heart rate (odds ratio = 1.03; 95% confidence intervals 1.006-1.05; p=0.001), maximal ST elevation (odds ratio =1.25; 95% confidence intervals 1.10–1.43; p=0.0001), QTc Bazett (odds ratio = 1.01; 95% confidence intervals 1.006–1.02; p=0.002), QT dispersion (odds ratio = 1.02; 95% confidence intervals 1.002–1.04; p=0.02) and both Tpeak-to-Tend and Tpeak-to-Tend/QT (odds ratio = 1.02; 95% confidence intervals 1.01–1.03; p<0.0001 and OR = 1.07; 95% confidence intervals 1.03–1.11; p<0.0001 respectively) were significantly associated with ventricular arrhythmias and arrhythmic mortality. Of note, Tpeak-to-Tend /QT remained a predictor of early ventricular arrhythmias and arrhythmic death (odds ratio = 1.04; 95% confidence intervals 1.003 – 1.10; p=0.03) independently from heart rate and maximal ST elevation. Receiver operating characteristic curve analysis showed that Tpeak-to-Tend /QT values <0.31 had a predictive negative value of 92% for the prediction of the composite outcome. Conclusions: Tpeak-to-Tend /QT was an independent predictor of early ventricular arrhythmias and arrhythmic mortality in patients with anterior ST elevation myocardial infarction. Especially, Tpeak-to-Tend /QT <0.31 may identify a subgroup of ST elevation myocardial infarction patients with low risk of early arrhythmias and arrhythmic death.

Comparison of different pharmacological interventions on enzymatic parameters during acute myocardial infarction

The concept that acute myocardial infarction is a dynamic event and that different interventions can modify the extent of the necrosis, has led to renewed interest in early pharmacological and surgical treatments designed to reduce the ischemic injury. To evaluate the effects of different pharmacological interventions aimed to reduce the extent of necrosis, we studied 166 patients (138 male and 28 female, mean age of 59.4 +/- 11.3 years) admitted within 6 h after chest pain and treated with a single therapy during the first 72 h. Enzymatic infarct size (IS) was calculated by serial creatine kinase isoenzyme MB determinations using a compartmental model. Six groups of patients were evaluated: 33 patients were treated only with antiplatelet drugs, 38 with anticoagulants, 34 with intravenous thrombolytic therapy, 20 with calcium channel blockers, 25 with nitrates, and 16 with beta-blockers. Estimated IS (gEq/m2) and elimination constant (Kd, U/L/h) did not differ in the six groups, but patients treated with streptokinase had higher release constant (Ka, U/L/h) and shorter time to peak CK-MB value. Early treatment (less than or equal to 2 h after chest pain) had a favourable effect on the enzymatic IS only in patients treated with calcium channel blockers (p less than 0.005).

Coronary artery vasomotion and post-stenotic coronary artery blood flow after intracoronary lacidipine in patients with ischaemic heart disease a pilot study

AbstractBackground: The calcium antagonist lacidipine has been shown to be highly vasoselective and to improve myocardial perfusion in hypertensive patients. However, its effects on coronary artery vasomotility and on post-stenotic coronary flow reserve in patients with atherosclerotic heart disease are unknown. Objectives: This study was designed to investigate the acute direct effects of repeated infusions of lacidipine on epicardial coronary artery vasomotion and on post-stenotic coronary artery blood flow in patients with stable angina pectoris and angiographic evidence of coronary heart disease. Methods: In 8 patients with stable angina and moderate to severe stenosis of the left coronary artery, measurements of epicardial dimensions (quantitative angiography) and of coronary blood flow (Doppler guidewire) distal to a stenosis were performed at baseline and after 3 repeated intracoronary boluses of 12μg of lacidipine. Results were compared with those obtained after 10mg of intracoronary papaverine. Results: The intracoronary administration of lacidipine was well tolerated, without any adverse effects. Lacidipine significantly increased the minimal luminal diameter of the lesion (peak relative increase of 43.7%), without significant changes in heart rate and systolic aortic pressure. Intracoronary lacidipine caused a dose-dependent increase in coronary flow reserve. Maximal vasodilatory effects were equivalent to those obtained with intracoronary papaverine. Conclusions: These results suggest that lacidipine acts directly as a potent vasodilator in stenotic epicardial vessels and improves myocardial perfusion distal to a moderately severe stenosis in patients with stable angina.

Dynamic changes of repolarization abnormalities in takotsubo cardiomyopathy.

Objective This study analyses dynamic changes in dispersion of ventricular repolarization over the time course of takotsubo cardiomyopathy (TC), and their relationships with clinical features and life-threatening arrhythmias. Methods and results All consecutive patients admitted to our division between January 2008 and December 2011 with a diagnosis of TC were analysed. Patients with prior myocardial infarction, symptoms-onset-to-admission time greater than 12 hours, an implanted pacemaker, or under treatment with drugs aff ecting QT interval, were excluded. Standard 12-lead ECG recordings during the acute, subacute and chronic phases were collected for each patient. Twentyfour patients (23 women, 63 ± 14 years) were included in our analysis. Only one patient experienced ventricular arrhythmias (4.2%). Signifi cant increases were observed in QT and QTc intervals (from 420 ± 423 to 505 ± 66 ms, P < 0.00001, and from 479 ± 33 to 551 ± 51 ms, P < 0.00001, respectively), QT dispersion (from 59 ± 18 to 100 ± 44 ms, P = 0.0006), Tpeak-to-Tend (from 82 ± 20 to 123 ± 39 ms, P = 0.00006) and Tpeak-to-Tend/QT (from 0.20 ± 0.33 to 0.26 ± 0.57, P = 0.0003) during the subacute phase. All these parameters returned to baseline values in the chronic phase and did not show any signifi cant diff erences between the acute and chronic phases. Conclusions A marked increase in QTc, QT dispersion, Tpeak-to-Tend and Tpeak-to-Tend/QT was observed during the subacute phase; this increase was transient and reverted in all patients before hospital discharge. Of note, these fi ndings were not associated with an increased risk of life-threatening arrhythmias.

Quantitative angiographic identification of functional left ventricular aneurysms

Thirty-three 30 degrees RAO left-ventricular angiograms with postinfarction aneurysms were analyzed to determine whether some quantitative variables could describe their morphological characteristics. Seventeen aneurysms were classified as functional (localized without a clear neck), and 16 as true (with a saccular shape). Left-ventricular volumes and global ejection fractions did not differ between the two types. The volume of functional aneurysms as a fraction of global end-diastolic volume was significantly larger (24.4+or-10.6% versus 13.2+or-8.5%, p=0.01). The end-systolic shape of ventricles with a functional aneurysm was more circular (77+or-6 versus 71+or-7, p<0.05) and showed a significantly smoother transition between contractile and noncontractile regions in the anterior site. The anatomic characteristics of resected areas in operated patients were similar in the two types of aneurysms.<<ETX>>

Update on mechanical revascularization in acute myocardial infarction: which role and when?

Mechanical revascularization in the acute myocardial infarction by primary angioplasty has several advantages over thrombolytic therapy. The short-term patency rates of the infarct-related artery range from 95 to 99% and a normal flow is achieved in more than 90% of the cases. This prompt and effective reperfusion is probably responsible for the improved prognosis with primary angioplasty. The better outcome after primary angioplasty is observed both in low- and in high-risk patients, in all ages and in patients presenting late (>6 h) after the chest pain. Pooled analysis of randomized studies, show that primary angioplasty as compared to thrombolysis, has a lower incidence of death, stroke and reinfarction. Additional advantages of primary PTCA include the possibility of reperfusion in patients in whom lysis is contraindicated or less effective (e.g. patients in cardiogenic shock, or with prior coronary artery bypass surgery) and the ability to provide prognostic information helpful in the patient triage. Thus, primary PTCA results in better outcome than thrombolysis when performed in centers with success rates comparable to those achieved in the randomized trials. Further studies are still needed to assess its long-term efficacy. Several randomized trials are underway to assess the role of stents and the use of more potent antiplatelet drugs, as the GPIIb/IIIa receptor blockers, in adjunct to balloon angioplasty in the treatment of acute myocardial infarction.