Epidemiological characteristics, management and early outcomes of acute coronary syndromes in Greece: The PHAETHON study.

INTRODUCTION: In view of recent therapeutic breakthroughs in acute coronary syndromes (ACS) and essential demographic and socioeconomic changes in Greece, we conducted the prospective, multi-center, nationwide PHAETHON study (An Epidemiological Cohort Study of Acute Coronary Syndromes in the Greek Population) that aimed to recruit a representative cohort of ACS patients and examine current management practices and patient prognosis. METHODS: The PHAETHON study was conducted from May 2012 to February 2014. We enrolled 800 consecutive ACS patients from 37 hospitals with a proportional representation of all types of hospitals and geographical areas. Patients were followed for a median period of 189 days. Outcome was assessed with a composite endpoint of death, myocardial infarction, stroke, urgent revascularization and urgent hospitalization for cardiovascular causes. RESULTS: The mean age of patients was 62.7 years (78% males). The majority of patients (n=411, 51%) presented with ST-elevation myocardial infarction (STEMI), whereas 389 patients presented with NSTEMI (n=303, 38%) or UA (n=86, 11%). Overall, 58.8% of the patients had hypertension, 26.5% were diabetic, 52.5% had dyslipidemia, 71.1% had a smoking history (current or past), 25.8% had a family history of coronary artery disease (CAD) and 24.1% had a prior history of CAD. In STEMI patients, 44.5% of patients were treated with thrombolysis, 38.9% underwent a coronary angiogram (34.1% were treated with primary percutaneous coronary intervention) and 16.5% did not receive urgent treatment. The pain-to-door time was 169 minutes. During hospitalization, 301 (38%) patients presented one or more complications, and 13 died (1.6%). During follow-up, 99 (12.6%) patients experienced the composite endpoint, and 21 died (2.7%). CONCLUSIONS: The PHAETHON study provided valuable insights into the epidemiology, management and outcome of ACS patients in Greece. Management of ACS resembles the management observed in other European countries. However, several issues still to be addressed by public authorities for the timely and proper management of ACS.

Short-term outcome and attainment of secondary prevention goals in patients with acute coronary syndrome--results from the countrywide TARGET study.

BACKGROUND/OBJECTIVES: Acute coronary syndromes (ACS) continue to pose a significant medical and socioeconomic burden worldwide. Optimal management strategy aims to improve short and long-term outcome. The present study aims to assess short-term outcome of real-world ACS patients and evaluate the achievement rate of secondary prevention goals. METHODS: The TARGET study is an observational study enrolling 418 consecutive ACS patients from 17 centers countrywide (78.0% males, 63.9 ± 12.9 years). After the in-hospital phase, patients were followed for 6 months. In total, 366 patients were included in the prospective phase of the study. At the end of the follow-up, mortality, major adverse cardiovascular events (MACE), prescription pattern of cardiovascular medications, lipid levels, adherence rate to treatment and behavioral recommendations were measured. RESULTS: The overall mortality was 4.8% and the rate of MACE was 17.5%. At 6 months, a significantly lower proportion of patients received antiplatelet agents and statins as compared to hospital discharge. At the end of the follow-up, 87.7% of patients remained on statin treatment, yet only 18.2% of patients had LDL cholesterol levels less than 70 mg/dL. The adherence pattern to lifestyle and dietary recommendations remained low (66.2% quit smoking, 55.8% and 81.3% followed physical activity and dietary recommendations respectively). CONCLUSION: Despite the low rate of mortality and MACE occurrence rate in this countrywide observational study, the attainment rate of secondary prevention goals is relatively poor. Improvement interventions focusing in these gaps of optimal care provision are expected to have a favorable impact on the prognosis of real world ACS patients.

Effect of angiotensin-converting enzyme inhibitors on systemic inflammation and myocardial sympathetic innervation in normotensive patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) may cause an increase in the inflammatory status and oxidative stress as well as sympathetic nervous system overactivity, even in the absence of any other organic heart disease. We investigated the effect of perindopril, an angiotensin-converting enzyme inhibitor (ACE-i), on indexes of systemic inflammation and oxidative stress in normotensive patients with type 2 DM. We also examined the effect of the drug on the disturbances of left ventricular myocardial adrenergic innervation that may be seen in these patients. We studied 62 normotensive patients with type 2 DM, who were randomized to receive perindopril (n=32) or placebo (n=30). At the start of the study and after 6 months' therapy blood samples were taken to evaluate total peroxides (TP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), and the patients underwent a (123)I-metaiodobenzylguanidine myocardial scintigraphy study. ACE-i caused a significant reduction in levels of cytokines and TP (P<0.001 for IL-6 and TNF-alpha, P=0.001 for TP). There was also a reduction in total defect score (P<0.001) and the heart to mediastinum ratio at 10 min and 4 h was improved (P<0.001 for both). No significant alterations were observed in the placebo group. Our data indicate that the addition of ACE-i to the medication of normotensive diabetic type 2 patients may improve the disturbed myocardial adrenergic innervation, the systemic inflammatory status and oxidative stress. Our findings indicate the cardioprotective action of ACE-i and suggest that earlier treatment might be appropriate in those patients.

Occupational exposure in the electrophysiology laboratory: quantifying and minimizing radiation burden.

Fluoroscopically guided procedures in the electrophysiology room, such as radiofrequency catheter ablation and implantation of cardiac resynchronization devices, may result in high radiation exposure of electrophysiologists and assisting staff. Our aim was to provide accurate and applicable data on occupational doses to the electrophysiology laboratory personnel. We exposed fluoroscopically an anthropomorphic phantom at three projections common in electrophysiology studies. For each exposure, scattered radiation was measured at 182 sites of the cardiology room at four body levels. Effective dose values, eye lens, skin and gonadal doses to the laboratory staff were calculated. Our study has shown that a procedure requiring 40 min of fluoroscopy yields a maximum effective dose of 129 microSv and a maximum value of gonadal dose of 56.8 microSv to staff using a 0.35 mm lead-equivalent apron. A conservative estimate of the electrophysiologist's annual maximum permissible workload is 155 procedures. Staff effective dose values vary by a factor of 40 due to positioning during fluoroscopy and by a factor of 11 due to radiation protection equipment. Undercouch protective shields may reduce gonadal doses up to 98% and effective dose up to 25%. Consequently, radiation levels in the electrophysiology room are not negligible. Mitigation of occupational exposure is feasible through good fluoroscopy and working practices.

Effect of acute atrial fibrillation on phasic coronary blood flow pattern and flow reserve in humans.

AIMS: To assess the effect of experimentally induced atrial fibrillation on coronary flow in humans. METHODS AND RESULTS: In 16 patients (10 men, mean age 43+/-13 years) with normal coronary vessels, baseline and hyperaemic blood pressure and Doppler phasic coronary flow velocity were measured, using a 0.014 inch intracoronary Doppler flow wire, during sinus rhythm, experimentally induced atrial fibrillation, and right atrial pacing at a similar heart rate to that during atrial fibrillation. Coronary flow velocity integral per minute increased significantly during both right atrial pacing and atrial fibrillation compared to sinus rhythm, but during right atrial pacing the increase was greater (85+/-43% vs 52+/-25%, P<0.001). This difference persisted even after correction for the product of heart rate and blood pressure (1.15+/-0.51 vs 0.97+/-0.46, respectively, P<0.02). In a further 12 paced patients (seven men, mean age 54+/-10 years) with complete atrioventricular block the induction of atrial fibrillation (atrial fibrillation with regular RR interval) caused no significant changes in coronary flow velocity variables. CONCLUSIONS: Acute atrial fibrillation in humans causes an increase in coronary flow that is, however, insufficient to compensate for the augmented myocardial oxygen demand, mainly because of the irregularity in the ventricular rhythm that exists during atrial fibrillation.

Left ventricular function and cardiopulmonary performance following surgical treatment of morbid obesity.

BACKGROUND: It is well established that morbid obesity affects the respiratory system and the diastolic function of the heart. During exercise, cardiopulmonary reserve is exhausted because of augmented requirements, leading to a significant intolerance. A study was undertaken to investigate the influence of body weight loss on the characteristics of the left ventricle (LV) and on exercise capacity in obese patients before and 6 months, following vertical banded gastroplasty (VBG). METHODS: 16 morbidly obese individuals (BMI > 40 kg/m2) scheduled for VBG were studied. A symptom-limited cardiopulmonary exercise test and a complete transthoracic echocardiogram were performed 1 day before operation and 6 months postoperatively (after the patients achieved a body weight loss of > 20% of their pre-operative values). RESULTS: Exercise duration increased significantly 6 months following surgery. The mean O2 consumption at peak exercise (peak VO2) and at the anaerobic threshold (VO2AT) was significantly higher after weight loss. 6 months after VBG the LV thickness decreased significantly. Regarding the diastolic indices, isovolumic relaxation time (IVRT) and early/late (E/A) velocity ratio, there was a significant improvement after weight loss. Simple linear regression analysis revealed that peak VO2 and VO2AT were significantly correlated with IVRT and E/A velocity ratio. CONCLUSIONS: Weight loss after VBG improves the cardiac diastolic function and this is associated with an improvement in cardiopulmonary exercise performance. Left ventricular filling variables could be considered among the most important determinants of exercise intolerance in obese individuals.

Conceptus radiation dose and risk from cardiac catheter ablation procedures.

BACKGROUND: The aim of the current study was to estimate the conceptus radiation dose and risk associated with fluoroscopic imaging during a catheter ablation procedure for supraventricular tachycardia performed on the expectant mother. METHODS AND RESULTS: Exposure parameters and fluoroscopy times for each projection of the cardiac ablation procedure performed in 20 female patients of childbearing age were recorded. Radiation doses for a potential conceptus were estimated by using dose data obtained in anthropomorphic phantoms simulating pregnancy at the first, second, and third trimesters. Dose measurements were carried out using thermoluminescent dosimeters. For a typical examination, the average radiation dose to the conceptus was <1 mGy in all periods of gestation. Average excess fatal cancer was 14.5/10(6) unborn children irradiated during the first postconception weeks. Corresponding values for the second and third trimesters were 30 and 55.7/10(6), respectively. The risk for hereditary effects in future generations was 1.5/10(6) cases for conceptus irradiation during the first postconception weeks. Corresponding values for the second and third trimesters were 3.0 and 5.6/10(6), respectively. Formulas and dose data are presented for estimating the conceptus risk from any technique and x-ray system used for catheter ablation procedures. CONCLUSIONS: A typical catheter ablation procedure results in a very small increase in risk of harmful effects to the conceptus. However, estimation of conceptus dose from catheter ablation procedures is always needed to assess the risk to the individual developing in utero.

Accurate assessment of patient effective radiation dose and associated detriment risk from radiofrequency catheter ablation procedures.

BACKGROUND: Radiofrequency (RF) cardiac catheter ablation procedures may require extended fluoroscopic exposure resulting in elevated radiation risk. The aim of the present study was to accurately establish RF ablation radiation risk levels and to provide means for accurate patient risk estimation from studies performed in any electrophysiology laboratory. METHODS AND RESULTS: Fluoroscopy required during cardiac ablation was classified into 4 types identified by beam orientation and irradiated tissue: (1) posteroanterior exposure during catheter advancing from the groin to the heart, (2) posteroanterior heart exposure, (3) left anterior oblique heart exposure, and (4) right anterior oblique heart exposure. The duration of each exposure was monitored in 24 patients undergoing RF cardiac ablation. Dose per minute of fluoroscopy was measured at 15 organs/tissues for each projection with the use of anthropomorphic phantom and thermoluminescence dosimetry. The effective dose rate was 219, 144, 136, and 112 mu/min for groin-to-heart posteroanterior, posteroanterior, left anterior oblique, and right anterior oblique exposure, respectively. A typical ablation procedure results in a total effective dose of 8.3 mSv per hour of fluoroscopy. The average excess of fatal cancers was estimated to be 650 and 480 per million patients undergoing RF ablation requiring 1 hour of fluoroscopy for US and UK populations, respectively. The average risk for genetic defects was determined to be 1 per million births. CONCLUSIONS: Radiation risk from RF cardiac ablation is moderate compared with other complications, but it may highly exceed radiation risk from common radiological procedures. Efforts should be made toward minimization of patient radiation risk from RF ablation procedures.

Myocardial perfusion in patients with permanent ventricular pacing and normal coronary arteries.

OBJECTIVES: The purposes of this study were to test the specificity of dipyridamole myocardial perfusion scintigraphy in patients with permanent ventricular pacing (PVP) and to evaluate coronary blood flow and reserve in these patients. BACKGROUND: Permanent ventricular pacing is associated with exercise perfusion defects on myocardial scintigraphy in the absence of coronary artery disease (CAD). On the basis of studies in patients with left bundle brunch block, coronary vasodilation with dipyridamole has been proposed as an alternative to exercise testing for detecting CAD in paced patients, but this approach has never been tested. METHODS: Fourteen patients with a PVP and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In these patients and in eight control subjects, coronary flow velocities were measured in the left anterior descending coronary artery (LAD) and in the dominant coronary artery before and after adenosine administration. RESULTS: In the paced patients, coronary flow velocities in the LAD and in the dominant coronary artery were significantly lower than those in the control subjects. In addition, seven patients showed perfusion defects on dipyridamole thallium-201 single-photon emission computed tomography, with a specificity of 50% for this test. The defect-related artery in these patients had lower coronary flow reserve (2.6 +/- 0.5) as compared with those without perfusion defects (3.9 +/- 1.0, p < 0.05) or the control group (3.5 +/- 0.5, p < 0.05). CONCLUSIONS: Permanent ventricular pacing is associated with alterations in regional myocardial perfusion. Furthermore, abnormalities of microvascular flow, as indicated by reduced coronary flow reserve in the defect-related artery, are at least partially responsible for the uncertain specificity of dipyridamole myocardial perfusion scintigraphy.

Relation of autonomic modulation to recurrence of atrial fibrillation following cardioversion.

The aim of this study was to investigate the time course of changes in autonomic nervous system activity in patients with long-standing atrial fibrillation (AF) following internal electrical conversion to sinus rhythm and to look for differences between patients who do and do not relapse. Time-domain indexes of heart rate variability were calculated from 24-hour Holter recordings on the day of conversion and 1 day and 1 month afterward for 22 patients with chronic (> 3 months) AF. Ten healthy subjects served as a control group. During the day of cardioversion the mean RR interval and its circadian variation differed significantly between controls and patients. The mean values of successive RR intervals that deviated by > 50% from the prior RR interval and the root-mean-square of successive RR interval differences--indexes of vagal modulation--were initially significantly higher in patients than in controls but showed a decrease (p < 0.05) by the second day (from 12.4 +/- 7% to 8.1 +/- 5% to 7.3 +/- 5% and from 49 +/- 9 to 39 +/- 12 to 41 +/- 11 ms, respectively) to levels similar to those of the controls (7.6 +/- 5% and 40 +/- 17 ms, respectively). Only these 2 indexes contained significant prognostic information about relapse: patients who later relapsed had higher initial values than those who did not, and these values remained high during the 2 days after conversion. In conclusion, this study provides data confirming that spontaneous chronic AF in humans results in a significant increase in vagal tone that is reversed with time after restoration of sinus rhythm. Persistently higher values of vagal tone are observed in patients who relapse, and are probably a predictor for recurrence.

Effect of pericardial pressure on human coronary circulation.

A 52-year-old patient underwent percutaneous balloon pericardiotomy because of rapid fluid accumulation. During the procedure, we calculated the amount of blood flow to the nondiseased left anterior descending coronary artery while pericardial pressure was gradually increased by the infusion of warmed normal saline solution. Coronary vasodilator reserve was assessed by intracoronary adenosine. With increasing pericardial pressure, there was a continuous decline in coronary blood flow, due to an increase in coronary vascular resistance, and an unaffected hyperemic response throughout. The maximal hyperemic flow was far less under increased pericardial pressure than at normal pressure, which implies an augmented susceptibility to myocardial ischemia.

Pulmonary tumor embolism from primary cardiac B-cell lymphoma.

We report the case of a 54-year-old man with pulmonary embolism during convalescence from "idiopathic" pericarditis. A transthoracic echocardiographic examination indicated a large mass within the right atrium. Subsequently, he died from refractory hypotension. On autopsy, two large whitish nodules were found in the right atrium; there was also nodular epicardial infiltration. Both lungs showed multiple, grossly visible tumor emboli with pulmonary infarction and no evidence of conventional thromboembolism. This is the first report of pulmonary tumor embolism due to large cell B-cell primary cardiac lymphoma. Refractory unexplained pericardial effusion, pulmonary embolism without risk factors for venous thrombosis, and/or the existence of a mass in the right heart should arouse clinical suspicion for this rare malignancy.

Phasic coronary flow pattern and flow reserve in patients with left bundle branch block and normal coronary arteries.

OBJECTIVES: The purpose of this study was to determine whether scintigraphic myocardial perfusion defects in patients with left bundle branch block (LBBB) and normal coronary arteries are related to abnormalities in coronary flow velocity pattern and/or coronary flow reserve. BACKGROUND: Septal or anteroseptal defects on exercise myocardial perfusion scintigraphy are common in patients with LBBB and normal coronary arteries. METHODS: Thirteen patients (7 men, age 61+/-8 years) with LBBB and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In all patients and in 11 control subjects coronary blood flow parameters were calculated from Doppler measurements of flow velocity in the left anterior descending coronary artery (LAD) before and after adenosine administration. RESULTS: The time to maximum peak diastolic flow velocity was significantly longer both for the seven patients with (134+/-19 ms) and for the six without (136+/-7 ms) exercise perfusion defects than for controls (105+/-12 ms, p < 0.05), whereas the acceleration was slower (170+/-54, 186+/-42 and 279+/-96 cm/s2, respectively, p < 0.05). Coronary flow reserve in the patients with exercise perfusion defects (2.7+/-0.3) was significantly lower than in those without (3.7+/-0.5, p < 0.05) or in the control group (3.4+/-0.5, p < 0.05). CONCLUSIONS: Patients with LBBB have an impairment of early diastolic blood flow in the LAD due to an increase in early diastolic compressive resistance resulting from delayed ventricular relaxation. Furthermore, exercise scintigraphic perfusion defects in these patients are associated with a reduced coronary flow reserve, indicating abnormalities of microvascular function in the same vascular territory.

The effect of DDD pacing on ergospirometric parameters and neurohormonal activity in patients with hypertrophic obstructive cardiomyopathy.

This study examined the acute and long-term effects of DDD pacing on ergospirometric parameters and neurohormonal activity in patients with hypertrophic obstructive cardiomyopathy (HOCM). We studied eight patients (five males), aged 56 +/- 7 years, with HOCM refractory to drugs. In all patients a DDD pacemaker was implanted and programmed with an atrioventricular (AV) delay that insured full ventricular activation. The patients underwent echocardiographic examination and exercise stress testing before and 3 days, 3 months, and 12 months after pacemaker implantation. Oxygen consumption was measured at the anaerobic threshold (VO2AT) and peak exercise (pVO2). Atrial natriuretic peptide (ANP) and cyclic adenosine monophosphate (c-AMP) levels were measured concomitantly. Left ventricular outflow tract (LVOT) pressure gradient decreased significantly from 70 +/- 18 to 25 +/- 12 mmHg (P < 0.05) 3 days after pacing and remained unchanged at 3 and 12 months. pVO2 and VO2AT increased significantly, from 20.1 +/- 3 to 23.4 +/- 3 mL/kg/min and from 16 +/- 3 to 17.8 +/- 2 mL/kg/min, respectively (P < 0.05). This improvement continued up to 3 months, and then remained stable until the end of the 12-month follow-up period. ANP levels decreased at 3 days from 85.4 +/- 5.7 to 75.4 +/- 7.3 fmol/mL (P < 0.05), and remained unchanged over the 12 months. c-AMP levels did not change significantly after the onset of pacing. DDD pacing in patients with HOCM not only reduces the LVOT pressure gradient but also causes a significant early and long-term improvement in exercise capacity and neurohormonal profile.

Spectral analysis of heart rate variability during tilt-table testing in patients with vasovagal syncope.

Spectral analysis of heart rate variability was used to assess changes in autonomic function in 44 patients with vasovagal syndrome and 20 normal controls before and during postural tilt and to attempt to relate such changes to specific types of haemodynamic response to tilt. Frequency domain measurements of the high (HF) and low (LF) frequency bands and the ratio LF/HF were derived from Holter recordings, computed by Fast Fourier Analysis for 4 min intervals immediately before tilt testing, immediately after tilting and just before the end of the test. In the syncopal patients the mean values of LF and HF decreased significantly in response to tilting, while the LF/HF ratio remained constant. All parameters showed a statistically significant increase just before the onset of syncope. In the control group there was an increase in the LF and LF/HF ratio and a decrease in the HF immediately after tilting. The three subgroups of patients had similar patterns of changes in autonomic activity. The results of this study show that syncopal patients have a different pattern of response to the tilting test. The pathological mechanism leading to vasovagal syncope appears to be independent of the specific type of haemodynamic response to tilt testing.