Mario Stanislao

Feasibility and Diagnostic Accuracy of a Gated SPECT Early-Imaging Protocol: A Multicenter Study of the Myoview Imaging Optimization Group

The aim of this study was to investigate whether early (time 1, or T1) myocardial tetrofosmin imaging is feasible and as accurate in detecting coronary artery disease as is standard delayed (time 2, or T2) imaging. Methods: One hundred twenty patients (100 men and 20 women; mean age ± SD, 61 ± 10 y) with anginal symptoms underwent tetrofosmin gated SPECT. Stress/rest T1 imaging was performed at 15 min and T2 at 45 min after injection. Image quality was visually evaluated using a 4-point scale (from 0 = poor to 3 = optimal). Myocardial perfusion analysis was performed on a 20-segment model using quantitative perfusion SPECT software, and reversible ischemia was scored as a summed difference score (SDS). Coronary angiography was performed within 1 mo on all patients, and stenosis of more than 50% of the diameter was considered significant. Results: Overall, quality was scored as optimal or good for 94% of T1 images and 95% of T2 images (P = not statistically significant). Heart, lung, liver, and subdiaphragmatic counts did not differ for stress and rest T1 and T2 imaging. A good linear relationship was seen between T1 and T2 SDS (r = 0.69; P < 0.0001), and Bland–Altman analysis showed good agreement between the 2 conditions. In terms of global diagnostic accuracy, areas under the receiver-operating-characteristic curve were comparable between T1 and T2 (0.80 vs. 0.81, P = not statistically significant). Discrepancies between T1 and T2 SDS were observed in 44% of patients (T1 − T2 SDS > 2). Linear regression analysis showed a good correlation between T1 and T2 SDS (r = 0.67; P < 0.0001), whereas the Bland–Altman method showed a shift in the mean value of the difference of +2.67 ± 2.73. In patients with a T1 − T2 SDS of more than 2, areas under the receiver-operating-characteristic curves were significantly higher for T1 than for T2 images (0.79 vs. 0.70, P < 0.001). Conclusion: T1 imaging is feasible and as accurate as T2 imaging in identifying coronary artery disease. However, in a discrete subset of patients, early acquisition strengthens the clinical message of defect reversibility by permitting earlier, more accurate identification of more severe myocardial ischemia.

Prevalence of Tako-Tsubo Syndrome among patients with suspicion of acute coronary syndrome referred to our centre

BACKGROUNDnThe Tako-Tsubo Syndrome is a clinical entity characterized by acute but rapidly reversible left ventricular systolic dysfunction and triggered by emotional or psychological stress. The aim of our study was to determine the prevalence and characteristics of this syndrome among the patients presenting to our Centre with suspicion of acute coronary syndrome.nnnMETHODS AND RESULTSnOver a 12-month period (May 2006 to April 2007), among 82 patients referred to our catheterization laboratory with suspicion of acute coronary syndrome, 4 confirmed Tako-Tsubo Syndrome (prevalence 4.87%). The patients referred to our Centre came from Foggias province above all. The mean age of the population was 65.5 +/- 18.48 years (range 49 to 82), with a ratio of men to women of 1:3. The syndrome characterized by acute chest pain with ST-segment elevation, absence of significant lesions in each of the 3 epicardial coronary arteries by angiography, systolic dysfunction (ejection fraction 35 +/- 9.12%) with abnormal wall motion of the mid and distal LV and hyperkinesia of the basal LV, and emotional or psychological stress immediately preceding the cardiac events. Among markers of cardiac necrosis, only serum Troponin-I increased in each patients without significant elevation of CPK and with mild elevation of CK-mb and LDH. 2 patients developed hemodynamic instability. Each patient survived with normalized ejection fraction (54.25 +/- 5.05%) and rapid restoration to previous functional cardiovascular status within 4 weeks.nnnCONCLUSIONSnA reversible cardiomyopathy triggered by emotional or psychological stress occurs in elderly women above all and mimic acute coronary syndrome. The diagnosis of Tako-Tsubo Syndrome is based mainly on coronary and left ventricular angiography, which excludes the diagnosis of coronary artery disease and recognizes the pattern of wall-motion abnormalities. The different epidemiology of this Syndrome reported in literature demonstrates which this cardiomyopathy is underdiagnosed.

Intravenous mexiletine in management of lidocaine-resistant ventricular tachycardia

In coronary care unite, intense activity is directed toward the recognition and suppression of those ventricular arrhythmias which are thought to herald ventricular fibrillation. Ventricular fibrillation is the most common cause of death in the early phase of myocardial infarction, as well as in chronic ischemic heart disease. In some cases it is preceded by ventricular tachycardia, but in others it occurs unexpectedly. Sustained ventricular tachycardia represents a significant problem in the initial care of patients with cardiac disease. Despite comparative safety and effectiveness, lidocaine appears to be less effective during the early phase of acute myocardial infarction.1*2 Although adequate serum levels may often not be achieved with standard doses, in some patients the ventricular arrhythmia appears to be truly “lidocaine resistant.“3*4 Alternative antiarrhythmic drugs, including procainamide, propranolol, and phenytoin, are variably effective. Intravenous disopyramide appears to be an effective antiarrhythmic drug in suppressing serious ventricular arrhythmias, including those not responsive to lidocaine.5 However, the patients with myocardial infarction who have low levels of systemic blood pressure are at increased risk of disopyramide-induced cardiac depression.6*7 Clearly, additional agents are desirable. Mexiletine is a new antiarrhythmic drug, available in oral and intravenous form, that is structurally and electrophysiologically similar to lidocaine. Experimental studies show that it is a quinidine-like drug from group II.8 Clinical studies have shown intravenous mexiletine to be safe and effective in suppressing ventricular arrhythmias that occurred in patients with acute and chronic heart disease as well as in patients with other acute clinical conditions.g-16 This report deals with the clinical evaluation of intravenous mexiletine in a study designed to assess its antiarrhythmic efficacy for emergency treatment of lidoCaine-resistant ventricular tachycardia. A total of 18 patients, 15 men and 3 women, with sustained lidocaine-resistant ventricular tachycardia were entered into the study. Their ages ranged from 40 to 60 years (mean 47 years). Clinical information on these patients is given in Table I. Acute myocardial infarction was present in eight patients; ventricular tachycardia

Mithridates VI Eupator of Pontus and mithridatism

We greatly appreciated the paper by Ring and Gutermuth, ‘100 years of hyposensitization: history of allergen-specific immunotherapy (ASIT)’ (1). Some points referring to Mithridates VI of Pontus deserve, in our opinion, to be further addressed (e.g. ‘... King Mithridates... used increased doses of snake venom to make himself immune against the toxin...’). Mithridates VI (132-63 BC), who ruled the northern part of Anatolia and waged a hard-fought war against the Romans, was interested, like other hellenistic sovereigns, in science, particularly poisons and antidotes (Fig. 1). His celebrated ‘universal antidote’ later came to be known as ‘Mithridatium’ (2). Aulus Gellius (Attic Nights 17.16) states that Mithridates used to mix the blood of Pontic ducks, whose flesh was toxic from their ingestion of plants poisonous to humans, with other substances reputed to ‘expel’ poisons. He also apparently obtained immunity to otherwise fatal doses of arsenic by ingesting tiny amounts over many years. His ‘theriac’ recipe was said to contain more than 50 ingredients, consisting of poison counteracting ‘drugs’ (3). He was known to display his ‘immunity’ to poison plots at banquets, inviting his guests to sprinkle his food and drink with deadly substances. Dio Cassius (Roman History 37.13) reports that Mithridates protected himself by taking his secret ‘antidote’ formula every day. Pliny the Elder (Natural History 25.3) states that Mithridates, through experiments, came up with a daily regimen of taking poison along with ‘remedies’. Appian (Mithridatic Wars 12.16) says that Mithridates accustomed himself to poisons by taking small doses every day. The original formula of the famous mithridatium has not survived, but it is unlikely that a snake venom was employed, as stated by Ring and Gutermuth. In fact, because of the enzymatic/proteic nature of their lethal active principia, reptile venoms taken orally are inactivated by proteolysis in the gut, being able to exert their effects only in the presence of lesions of the inner surface of the first digestive tract. The fact that snake venom could be safely ingested was known in antiquity. For example, the Roman writer Lucan (Bellum Civile/Pharsalia 9.614) stated that ‘snake venoms are dangerous only when mixed to the blood’. The word ‘mithridatism’ is currently used to mean tolerance or unresponsiveness to a toxin, which is acquired by taking gradually larger doses of it. The reported continuous per os assumption of ‘hemetics, antidotes, poisons, remedies and/or (unspecified) drugs’ probably determined Mithridates’ resistance to toxins more by functional and/or metabolic changes than by immune mechanisms. In this regard, gut irritation (impairing the absorption of the poison itself as in the case of chronically taken low doses of arsenic) and/or induction/activation of drug-biotransforming enzymes are likely to have been involved. Such resistance was said to have resulted in an unwonted effect when, in 63 BC, Mithridates tried unsuccessfully to empoison himself to avoid to be captured alive by his enemies. Appian states that Mithridates ‘mixed’ the poison and shared the dose with his two young daughters, then swallowed the rest. The two girls died immediately, but Mithridates only became weak (Fig. 2). The composition of this suicide poison is unknown. The effectiveness of poison in rapidly killing Mithridates’ daughters following oral ingestion suggests a nonproteic nature of the poison itself and, therefore, it is unlikely that Mithridates’ tolerance was based on an immunological mechanism. He had shared the single dose with his two daughters and the remaining amount was sublethal, also due to his tolerance. Figure 1 Portrait of Mithridates VI Eupator by Cristiano M. Ferretti. Mithridates is represented as Hercules wearing a lionskin. The sketch was inspired by the sculpture at Louvre museum (courtesy of the artist). Allergy

Cardiac Arrest caused by Barlow's Syndrome or by Stress Cardiomyopathy?

We describe a case of out-of-hospital Cardiac Arrest (CA) in a patient with Barlows Syndrome (BS) and features of Stress Cardiomyopathy (SC) (or Apical Ballooning Syndrome or Tako-Tsubo). The patient experienced CA during physical stress and was resuscitated thanks to DC-Shock. The Electrocardiogram (ECG) after resuscitation was unremarkable. In the reported case the documented severe hypokalemia, with the physical stress, could have triggered the CA, probably of tachyarrhythmic origin. However, in the reported case, the echocardiographic, coronarographic and ventriculographic features, were surprisingly indistinguishable from those of the SC. In conclusion it is impossible to say if, in our patient, the CA has been caused by BS or by SC. However, even if CA has been probably caused by the BS, we hypothesize that the CA, in its turn determined, might have caused the SC via stress mechanisms. In few words, the CA is a complication of SC, but should probably be regarded also as a cause of SC.

Volume overload modulates effects of cardiac resynchronization therapy independently of myocardial reperfusion: results of the RESYNC study.

Objectives Cardiac resynchronization therapy (CRT) may induce significant changes in regional wall motion and perfusion. However, the link between these variables in patients with heart failure has not been investigated. Methods Thirty-six patients with idiopathic (n = 22) or ischemic (n = 14) cardiomyopathy (mean age 70 ± 8 years, 24 male) were studied by echocardiography and gated single-photon emission computed tomography (SPECT) before and within 2 months after CRT. Results New York Heart Association class improved in all but four patients. The perfusion analysis indicated that, in all but three patients, there was a significant improvement of tracer uptake. Baseline end-diastolic volume index obtained by gated SPECT modulated increase of ejection fraction (P < 0.001), reduction of end-systolic volume index (P < 0.01) and improvement of motion (P < 0.001), as well as of left ventricular wall thickening (P < 0.002). Finally, despite CRT inducing significant reperfusion independently of volume overload (P < 0.05), extension of perfusion defect correlated with global improvement in the follow-up (P < 0.05). Conclusions Volume overload may identify responders to resynchronization therapy. CRT induced a significant ‘reperfusion’ both in ischemic and idiopathic cardiomyopathies, even if this is not sufficient to improve left ventricular function in patients with more severe volume overload. Finally, simultaneous evaluation of volume overload and perfusion defects may result useful in identifying CRT responders.

Anomalous origin of the left coronary artery from the pulmonary artery in an elderly patient, football player in youth.

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital defect. Without surgical treatment, approximately 90% of infants die within the first year of life. Late presentation in the adult or elderly is rare. Factors that may lead to survival in advanced age include the development of intercoronary collaterals. Furthermore, the risk of sudden cardiac death due to ischaemic malignant ventricular dysrhythmias exists even in asymptomatic adult patients and, classically, is precipitated by exercise. We report the case of a 67-year-old man, a football player in his youth, always asymptomatic until presentation at our centre for symptomatic sustained ventricular tachycardia and shortness of breath on exertion. We show the features of the ECG, transthoracic echocardiography, angiography study of the coronary and the pulmonary system, myocardial basal and stress gated single photon emission computed tomography with Tc-tetrofosmin and cardiac CT 64 slices. The patient was referred to cardiac surgery. We believe that this patients favourable course may be ascribed to the large network of collaterals from the right coronary artery supplying the entire heart. However, the exact reason why these favourable evolutions (both vascular and clinical) occur only in some individuals remains largely unknown.

Analysis of agreement between dobutamine stress echocardiography and exercise nuclear angiography in severe aortic regurgitation

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Tolerability of Amlodipine

SummaryWe examined the tolerability and safety of amlodipine in a large population of patients (n = 12 831) by performing a meta-analysis of 16 consecutive studies in which this drug was used for treatment of hypertension (n = 9638; 75%) or ischaemic heart disease (n = 3193; 25%) and data were standardised and referred to a central core laboratory. Adverse events were reported by patients in response to an open questionnaire and completed at standardised times after starting amlodipine.Overall, the percentage of patients who experienced amlodipine-related adverse effects was about 15%, and only 3% of patients were withdrawn from amlodipine therapy because of drug intolerance.Four adverse events (peripheral oedema, headache, flushing and altered heart rate) occurred in 1% or more of amlodipine recipients; these are typical of dihydropyridines and are predominantly related to arteriolar vasodilation.Rare adverse events attributable to idiosyncratic or allergic response (skin rash) were reported.Other adverse events (gastrointestinal disorders, tremor, polyuria, cough, etc.) were ill defined, and their nature was unclear.Finally, the percentage of patients with amlodipine-related adverse effects was not influenced by drug dosage or disease status, and a comparison of amlodipine’s tolerability with that of alternative calcium antagonists, β-blockers or ACE inhibitors showed a significantly lower occurrence (17.3 vs 39.7% of patients, p < 0.001).

CRT in Patients with Heart Failure: Time Course of Perfusion and Wall Motion Changes.

In patients treated with CRT no data relative to the relationship between regional wall motion and perfusion and reverse remodelling of the left ventricle at short and medium term followup were available. To this aim, 36 heart failure patients were studied by G-SPECT before (T0), within 2 months (T1) and 6 months (T2) after CRT. A clinical followup was completed for 36 months. In 30/36 patients there was an improvement of NYHA Class at T1 that persisted at T2. G-SPECT showed significant improvement of perfusion at T1 in 92% of patients without further changes at T2. A reduction of LV volumes, an increase of EF and an improvement of regional wall motion and thickening were observed at T1 versus baseline, with only minor changes at T2. Moreover, baseline extension of perfusion defects was scarcely correlated with improvement after CRT. Finally, end diastolic volume, perfusion defect and diabetes mellitus were independent predictors of survival. The main effects of CRT on regional myocardial perfusion and wall motion are obtained within 2 months. Volume overload modulates recovery of ventricular function independently of reperfusion and, with extension of perfusion abnormalities and diabetes were independent predictors of survival during followup.