The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk.

OBJECTIVES: Fibroblast growth factor-23 (FGF-23) and vitamin D are hormones involved in phosphate homoeostasis. They also directly influence cardiomyocyte hypertrophy. We examined whether the relationships between levels of vitamin D or FGF-23, cardiac phenotype and outcome were independent of established cardiac biomarkers in a large cohort of community-dwelling elderly subjects. DESIGN AND SETTING: Plasma levels of FGF-23 and vitamin D were measured in 1851 men and women (65-84 years) resident in the Lazio region of Italy. Participants were referred to eight cardiology centres for clinical examination, electrocardiography, comprehensive Doppler echocardiography and blood sampling. All-cause mortality or hospitalizations were available after a median follow-up of 47 months with record linkage of administrative data. RESULTS: Vitamin D deficiency (<20 ng mL(-1) ) was found in 72.3% of subjects, but FGF-23 levels were normal [74 (58-97) RU per mL]. After adjustment for cardiovascular risk factors and morbidities, low concentrations of vitamin D and high levels of FGF-23 were associated with a higher left ventricular (LV) mass index. Levels of FGF-23 [hazard ratio (HR) (95% confidence interval (CI)) 1.71 (1.28-2.28), P < 0.0001] but not vitamin D [0.76 (0.57-1.01), P = 0.08] were independently associated with mortality after adjustment for clinical risk factors and two cardiac markers together (N-terminal pro-brain natriuretic peptide and high-sensitivity cardiac troponin T), but did not predict hospital admission. People with above median values of FGF-23 and below median values of vitamin D had greater LV hypertrophy and higher mortality. CONCLUSIONS: In community-dwelling elderly individuals with highly prevalent vitamin D deficiency, FGF-23 levels were associated with LV hypertrophy and predicted mortality independently of two robust cardiac biomarkers. A causal relationship was not demonstrated, but the hormones involved in mineral metabolism emerged as nontraditional risk factors and may affect cardiovascular risk.

High-sensitivity cardiac troponin T for detection of subtle abnormalities of cardiac phenotype in a general population of elderly individuals.

OBJECTIVE: To investigate the association between circulating cardiac biomarkers and minor abnormalities in cardiac phenotype [left ventricular (LV) mass and midwall fractional shortening (MFS)] in elderly individuals in a general population sample. DESIGN AND SETTING: We examined the relationship between plasma concentrations of high-sensitivity cardiac troponin T (hs-cTnT) or N-terminal probrain natriuretic peptide (NT-proBNP) and elevated LV mass (LV mass/body surface area >95 g m(-2) for women and 115 g m(-2) for men), reduced MFS (<15%) or isolated LV diastolic dysfunction in 1973 elderly subjects (mean age 73 ± 5 years, range 65-84) resident in the Lazio region of Italy and enrolled in the PREDICTOR study. RESULTS: Overall, 24.8% of subjects had elevated LV mass, and 30.4% had reduced MFS. Median [quartile 1-3] plasma concentrations of hs-cTnT and NT-proBNP were higher in individuals with elevated than those with normal LV mass: 6.6 [3.5-11.6] and 147 [64-296] ng L(-1) vs. 4.6 [3.0-8.1] and 79 [41-151] ng L(-1) respectively (P < 0.001). There was a graded increase in median hs-cTnT concentrations across clinical categories of LV hypertrophy: 4.6 [3.0-8.1], 5.8 [3.1-10.2], 7.6 [3.8-13.7] and 8.4 [3.8-17.6] ng L(-1) for subjects with normal LV mass and mild, moderate or severe LV hypertrophy respectively (P < 0.0001); hs-cTnT also increased with increasing quartiles of MFS or grades of isolated LV diastolic dysfunction. CONCLUSIONS: Within an extremely low range of concentrations, increased hs-cTnT amongst community-dwelling elderly subjects is associated with subtle alterations in cardiac phenotype, suggesting that minor injury to cardiac myocytes and subsequent release of troponin reflect subclinical pathophysiological LV deterioration in this population.

Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study.

BACKGROUND AND AIM: We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF≤45%) on optimal therapy (including ACE-i or ARB, and ß-blockers). METHODS AND RESULTS: From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI≥30kg/m(2) instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04

[Effects of aldosterone receptor blocker therapy on cardiac remodeling]. / Effetto sul rimodellamento cardiovascolare della inibizione recettoriale dell'aldosterone.

Cardiac remodeling is a physiologic or pathologic condition that occurs after myocardial infarction, pressure overload, myocardial inflammatory diseases, idiopathic dilated cardiomyopathy or volume overload. In spite of different etiologies, molecular, biochemical and mechanical processes are the same. The change in left ventricular function brings about a complex neuro-hormonal disorder, and disease progression is due to the combined action of several biological factors with toxic effects on the heart and vessels. The renin-angiotensin-aldosterone system (RAAS) is very important in this process, through the effects on hydro-saline balance or through direct processes on myocardium. A direct effect of aldosterone in myocardial fibrosis after the detection of heart tissue aldosterone production has been demonstrated. In the past, the attention of physicians and researchers was focused on angiotensin II inhibition; and therefore, on angiotensin-converting enzyme (ACE) inhibitors, considering them sufficient to antagonize the effects of aldosterone. Nevertheless, this theory has been confuted in recent studies, with the evidence of elevated plasmatic aldosterone levels in patients treated with ACE-inhibitors and angiotensin receptor blockers. This phenomenon probably is due to the activation of secondary ACTH mediated pathways of trial aldosterone production. It has been demonstrated that aldosterone receptor inhibition is effective in reducing cardiac remodeling and mortality. AREA-IN CHF is the first multicentric, double blind, randomized, placebo control study to compare canrenone, an aldosterone receptor blocker, with placebo. The primary end point is the echocardiographic evaluation of left ventricular remodeling. Secondary end points are left ventricular end-systolic volume, ejection fraction, diastolic filling patterns, NYHA functional class, and mortality and hospitalizations of cardiac origin. In addition, bio-humoral effects of aldosterone receptor blocker therapy will be investigated. The study results will be available at the end of 2006.

[Management control of cardiology: the experience of a departmental unit]. / Controllo di gestione della cardiologia: esperienza di una unità dipartimentale.

In most Italian hospitals, sanitary reform is being applied, while at the same time a new organization of the National Health System is being planned. The director of the medical hospital (head doctor) is becoming more and more involved in management and this aspect has modified his professional attributes. Cardiology is a branch of medicine that, through its scientific preparatory work consisting in debates, management courses, ethics, and production of managerial software, is closer to applying the reform without risking improper administrative aspects. This, obviously, comes about after thoroughly reviewing past work methods and the need to have an administrative organization, which allocates efficient use of manpower and materials, helping to eliminate any sources of inefficiency. The logical procedure foresees an actual analysis in terms of sanitary needs and availability of resources, and so attempting to better balance and harmonize both aspects of the problem. Certainly, the acquisition of theoretical norms and practices, which today are present because of the upsurge in training courses for doctors, is not enough to guarantee the achievement of optimal results. Furthermore, we find that theoretical models need to be validated and adapted to real work situations in the public hospital sector. This paper proposes, therefore, to explain the managerial experiences achieved in actual work situations at the Cardiology Department Unit of the San Giovanni Addolorata Hospital in Rome. In particular, it shows that in order to reach its clinical and economical objectives, it is essential to make available correct informative support for strategic and operational decisions. We can observe that there is a continuing lack of computer support systems being integrated into the present organization of most cardiology units. The use of software distributed to cardiology units from the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) has enabled us to partially remedy the above-mentioned inadequacy and, at the same time, has pointed out the limits of automated support with regards managerial needs which are rapidly changing and becoming increasingly more complex. The experience described shows the possibility of uniting an efficient organization, from a clinical point of view, with an adequate managerial automation without including any flaws from the previous organizational systems. Based on achieved results and the difficulties encountered, further development in computer technology support to hospital management is suggested. This paper, in particular, stresses the need to improve automated informative support available to doctors in managerial positions. This improvement would allow us to immediately evaluate "internal" administrative matters, have the data available for budget planning and analysis of budget variations, and be better able to integrate this with clinical data. The scientific community can give further assistance by promoting the genesis of data for a sensible bench-marking within medical organizations which is the only means sufficient to give reliable and clinically appropriate indications on the possibility of increasing its own structural efficiency.

Papillary muscle rupture: small life-threatening myocardial infarction.

We report the case of a 70 years old man admitted to our coronary care unit because of atrial fibrillation, non-ST-elevation myocardial infarction and cardiogenic shock. Emergency coronary angiography showed a 99 % stenosis of the circumflex coronary that was successfully treated with a bare metal stent. Atrial fibrillation was cardioverted to sinus rhythm. Nevertheless, no hemodynamic benefit was observed. Transesophageal echocardiography (TEE) showed rupture of the papillary muscle (PM). The patient underwent emergent mitral valve replacement. Surgical visualization of the mitral valve confirmed the rupture of the antero-lateral PM. The postoperative course was uneventful and the patient recovered fully. This case highlights that even small myocardial infarction may have dramatic clinical presentations such as PM rupture with cardiogenic shock. Clinical suspicion and rapid confirmation of the diagnosis by TEE are essential requirements for successful treatment.

Prognosis of patients with ischaemic cardiomyopathy after coronary revascularisation: relation to viability and improvement in left ventricular ejection fraction.

BACKGROUND: In patients with ischaemic cardiomyopathy and viable myocardium, left ventricular ejection fraction (LVEF) does not always improve after revascularisation. Whether this may affect prognosis is unclear. OBJECTIVE: To evaluate the prognosis of viable patients with and without improvement of LVEF after coronary revascularisation. METHODS: Before revascularisation, radionuclide ventriculography (RNV) and dobutamine stress echocardiography were performed to assess LVEF and myocardial viability, respectively. Nine to 12 months after revascularisation, LVEF improvement was assessed by RNV. Patients were divided into three groups: group 1, viable patients with LVEF improvement (n = 27); group 2, viable patients without LVEF improvement (n = 15), group 3, non-viable patients (n = 48). Cardiac events were evaluated during a 4-year follow-up. RESULTS: After revascularisation, the mean (SD) LVEF improved from 32 (9)% to 42 (10)% in group 1, but did not change significantly in group 2 and in group 3, p<0.001 by analysis of variance (ANOVA). Heart failure symptoms improved in both groups 1 (mean (SD) NYHA class from 3.1 (0.9) to 1.7 (0.7)) and 2 (from 3.2 (0.7) to 1.7 (0.9)), but not in group 3 (from 2.8 (1.0) to 2.7 (0.5)), p<0.001 by ANOVA. During follow-up, the cardiac event rate was low (4%) in group 1, intermediate (21%) in group 2 and high (33%) in group 3 (p = 0.01). CONCLUSION: The best prognosis after revascularisation may be expected in those viable patients whose LVEF improves. Conversely, viable patients without functional improvement have an intermediate prognosis.

[Role of cardiac first aid in a level-II Emergency Department]. / Ruolo del Pronto Soccorso Cardiologico in un Dipartimento di Emergenza di II livello.

We report our experience in the organization and management of a Cardiac First Aid Unit (CFAU) which was developed according to the guidelines of the National Hospital Cardiologists Association as a part of a General Emergency Department. The CFAU is a 24 hour service directed by a Senior Cardiologist. The medical facilities are two monitored beds for short-term observation (cardio-pulmonary resuscitation instruments, echocardiograph, endoesophageal pacing for overdrive). The main goals of CFAU are the treatment of cardiac emergencies (acute myocardial infarction, pulmonary oedema, threatening arrhythmias, etc.) and the screening of patients presenting with chest pain or symptoms suggesting cardio-vascular involvement. In one year, there were 1700 admissions to the CFAU (3.7% of the total Medical Emergencies). The frequency of hospital admissions was 81% and coronary heart disease accounted for 38.3%. A sample of 100 consecutive patients with acute myocardial infarction admitted in the period October-November 1996 was examined to explore the impact of a CFAU on in-hospital delay in the application of thrombolysis. Thirty-nine patients were treated with thrombolysis, 15 in CFAU and 24 in Coronary Care Unit (CCU). The mean in-hospital delay to thrombolysis was 30 +/- 14 minutes for those treated in CFAU and 55 +/- 12 minutes for those treated in CCU (p < 0.0004). In a second sample of 100 consecutive patients with undetermined chest pain, by means of our protocol of short observation we identified 22 cases of acute myocardial infarction (AMI), 8 cases of angina pectoris, 18 various cardiac causes, 30 non-cardiac causes, 22 absent disease. ECG was obtained in all 100 pts, cardiac enzymes in 74, echocardiogram and chest X-ray in 48, ST monitoring in 26. In no case was diagnosed AMI after discharge. Cardiac First Aid Unit, as designed in our Hospital, suits the needs of a level II Emergency Department. It is a useful tool to shorten in-hospital delay to thrombolysis and to screen chest pain with nearly complete safety.

[An echocardiographic problem: the interventricular septum thickness in hypertrophic obstructive cardiomyopathy (author's transl)]. / Un problema di ecocardiografia. Lo spessore del setto interventricolare nella cardiomiopatia ipertrofica ostruttiva.

Peripheral venous contrast echocardiography is an established method in the assessment of cyanotic congenital heart diseases and for the exact definition of the inner cardiac surfaces outlines. We found it extremely useful in order to correctly delineate the right border of the interventricular septum in IHSS. The method showed that the interventricular system thickness had been underestimated in five out of six patients.

Ventricular dynamics after surgical closure of VSD.

Twenty patients varying in age between 5 and 20 years at the time of surgical closure of VSD were studied 2 to 9 years postoperatively. Ventricular function was studied by echocardiography and measurement of systolic time intervals for the left and right ventricles and the findings were related to clinical and haemodynamic results of operation. The VSD was closed in all instances and the haemodynamic situation was normalized in all but 2 patients who had persisting pulmonary vascular disease. Right bundle branch block (RBBB) was recorded in 11 instances and in 5 there was an associated left axis deviation (LAD), suggesting left anterior hemiblock. LAD occurred as an isolated anomaly in another 2 patients. The heart size was within normal limits in all the patients. Abnormal septal motion (ASM) was recorded in 13 of the 20 patients, but other echocardiographic analyses, such as LV end-diastolic dimension, left atrial/aortic root ratio, posterior wall velocity index and maximal endocardial velocity, were all within predicted normal limits. There was an almost uniform prolongation of both left and right pre-ejection periods. left and right ejection period as a rule remained normal and gave an increased PEP/ET ratio, indicating the presence of postoperative ventricular dysfunction also in instances with complete normalization of the haemodynamic situation. Suggested background mechanisms for these findings are the frequent occurrence of conduction defects postoperatively, the likelihood of altered ventricular compliance and possibly also as a cause of ASM postoperative presence of an opened pericardial sac.

[Echocardiographic diagnosis of the dissection of the thoracic aorta]. / La diagnosi ecocardiografica di dissezione dell'aorta toracica

Nine patients with aortic root dilatation without dissection and four patients with a dissecting aneurysm of the ascending aorta were studied with single-plane echocardiography. Previously reported echocardiographic findings, which have been shown to be similar in these two groups of patients, are confirmed. In addition to (a) aortic root dilatation, (b) thickening of the anterior and/or the posterior aortic wall, and (c) the multiple parallel echoes within the widened aortic walls, which are all considered to be not specific signs of dissection, the authors outline the presence of some specific echocardiographic patterns in patients with a dissecting hematoma of the ascending aorta. These include: 1) the loss of contiguity between the inner borders of the anterior aortic wall and the interventricular septum when the dissection is confined to the anterior wall of the aorta; 2) the loss of contiguity between the inner and/or outer borders of the posterior aortic wall and the mitral anulus if the hematoma extends to the posterior wall of the aorta.

[Clinical application of echocardiokymography for detection of global and sectorial dyskinesias (author's transl)]. / Applicazioni dell'ecocardiochimografia nello studio delle ipo-discinesie globali e settoriali.

The clinical application of a new ultrasonic technique, echocardiokymography (ECKG), has been showed particularly useful in the detection of myocardial and pericardial dyskinesias. In patients with congestive cardiomyopathy, the global hypokynesia was confirmed by the ECKG; regional impairment of parietal wall motion after myocardial infarction is clearly demonstrated by the technique; acute and chronic pericarditis show peculiar kymographic patterns. The ECKG is a kind of two-dimensional examination, that keeps some of the advantages of the time-motion, in the comparative study of cardiac walls dynamics.

[Patent double aortic arch and congenital mitral insufficiency (author's transl)]. / Doppio arco aortico funzionante e insufficienza mitralica congenita

A case of double aortic arch with severe congenital mitral incompetence and mild pulmonary arteries stenosis is described. A possible embriogenetic explanation of the anomaly is discussed in the light of preferential foetal blood flows.

[Clinical, electrocardiographic and echocardiographic findings in a case of vasospastic angina with alternating pseudonormalization of the ST segment]. / Rilievi clinici, elettrocardiografici ed ecocardiografici in un caso di angina vasospastica con pseudo-normalizzazione alternante del tratto ST.

During Ergonovine-test a patient with Prinzmetal angina presented (in I, aVL, V3-V6) ST downsloping which, after a temporary phase of alternative normalization (AST) beat to beat in V5, progressed to ST upsloping with typical angina. The M-mode echo-study first discovered, before than ecg, septal impairment (hypokinesia which increased to akinesia in the AST phase) and also asynergy of posterior wall of left ventricle. After intravenous nitrate echo-alterations reversed more rapidly than ecg one (transitional phase of ST decrease). The authors relate the AST to temporary alternative pseudonormalization caused by a phase of electrical instability during progressive vasospastic ischemia involving first the endocardial layers and after the epicardium of a single myocardiocoronary district. Probably also other partially opposite ischaemic districts, as suggested from echo data of posterior wall asynergy took a part in these events. This rare ST-alternans type as new pseudonormalization phenomenon and the usefulness of echo-study during ischaemic attacks are stressed.

[Hypertrophic cardiomyopathy associated with Noonan's syndrome and membranous aortic subvalvular stenosis associated with Turner's syndrome. Report of 2 clinical cases]. / La cardiomiopatia ipertrofica associata alla sindrome di Noonan e la stenosi sottovalvolare aortica membranosa associata alla sindrome di Turner. Rapporto su due casi clinici.

Cardiovascular anomalies are found in 50% of the cases of Turner's and Noonan's syndromes-diseases with the same phenotype but with a different genotype. In the former, the most common congenital heart diseases are aortic coarctation (30%) and bicuspid aortic valve (34%), while in the latter they are pulmonary valvular stenosis (60%), interatrial septal defect (25%) and obstructive or non obstructive hypertrophic cardiomyopathy (17%). We have described two cases, respectively of Noonan's and Turner's syndrome. The prominent features of the first case are the transmission of the syndrome on the male line, since father and son--the latter being our patient--are affected with the same syndrome, and the occurrence of a non obstructive hypertrophic cardiomyopathy involving both the ventricles, a situation not yet described in Noonan's syndrome. A subvalvular membranous aortic stenosis has instead been found in our patient with Turner's syndrome: this cardiac anomaly has never been described within the aforementioned syndrome in medical literature.

Addition of captopril versus increasing diuretics in moderate but deteriorating heart failure: a double-blind comparative trial.

In 15 patients with moderate congestive heart failure not completely controlled on digoxin (0.25 mg o.d.) and frusemide (25 mg o.d.), we compared the addition of captopril (12.5 to 50 mg b.i.d.) with increasing doses of frusemide (25 to 100 mg o.d.), in a randomized double-blind, double-dummy, comparative trial. Thirteen patients completed the 3 months study: two dropped-out in the frusemide group. Statistically significant clinical improvement occurred in both treatment groups. Exercise tolerance also significantly improved in both groups in a parallel fashion. Echocardiographic cardiac function data showed a significantly better pattern of changes in the captopril group. The addition of low doses of captopril to basal therapy seems to be as effective as the addition of high doses of frusemide in uncontrolled moderate congestive heart failure. This approach with captopril also appears to be more physiological and safe.

[Anatomo-functional study of non-rheumatic mitral insufficiency with transesophageal echocardiography]. / Studio anatomo-funzionale dell'insufficienza mitralica non reumatica con ecocardiografia transesofagea.

Reconstruction surgery of the mitral valve has become an alternative to mitral replacement in patients with pure mitral regurgitation. Preoperative assessment of the anatomic and functional aspects of the valvular lesion is of the utmost importance in conservative surgery. Transesophageal echocardiography is a new approach to investigating the mitral valve, and our study was undertaken with the purpose of determining its importance in the exploration of mitral regurgitation of non-rheumatic origin. Subjects included were twenty patients with pure and isolated mitral regurgitation (MR): 14 males and 6 females with an average age of 47 +/- 13 years. All the patients underwent a first transesophageal 2D and color Doppler echocardiographic examination, and 5 of them underwent a second one during cardiovascular surgery. Mitral anulus diameter, mitral valve cordae tendinae status, valvular leaflet length and coaptation were examined and color Doppler regurgitation jet area was measured. Mitral anulus diameter was 40.2 +/- 8.06 mm (diastolic) and 41.9 +/- 8.53 mm (systolic) and was above the values considered to be normal. Anterior leaflet length was 30.8 +/- 3.12 mm and posterior leaflet length was 22.9 +/- 4.74 mm; regurgitation jet area was between 1.2 cm2 and 13.52 cm2 with an average of 5.44 cm2. In the group with MR of mixomatous origin, systolic anulus diameter showed a linear correlation with regurgitation jet area (r = 0.79). In the 6 patients who underwent cardiac catheterization, angiographic semiquantitative evaluation of the MR confirmed that based on color Doppler jet area. In all twenty patients transesophageal echocardiography enabled us to identify the mechanism responsible for mitral insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pulsed Doppler echocardiography in the study of tricuspid valve insufficiency]. / L'ecocardiografia Doppler ad onda pulsante nello studio della insufficienza tricuspidale.

The value of pulsed Doppler echocardiography in assessing the presence and severity of tricuspid regurgitation (TR) has been studied in three groups of subjects, 12 without cardiovascular disease (Group I), 38 with TR (Group II) and 16 patients with aortic and mitral valve disease but no TR (Group III). The presence and severity of TR was also independently evaluated by clinical examination, jugular vein pulse recording and/or hemodynamic investigation. Left parasternal, sub-xyphoid and apical views were adapted for the pulsed Doppler echocardiographic examination. The sample volume was placed in the right atrium at varying distances from the tricuspid valve. We tried to quantitate the degree of TR according to: 1) the diameter and maximal distance from the tricuspid valve of the regurgitant stream, 2) the duration of reguritation through systole, and 3) the degree of turbolence as demonstrated by the time interval histograms. On the basis of above mentioned criteria, three subgroups of subjects with TR, i.e. mild, moderate and severe were recognised. These results were compared to hemodynamic and/or clinical-poligraphic evaluation. In 34 Group II subjects (89%), the Doppler study revealed the presence of TR and allowed an acceptable quantitative assessment. Falsely positive diagnoses were not made in any of the subjects of Group I. Identification of organic TR in patients with atrial fibrillation was possible only when regurgitation was moderate or severe.

Incidence of compensatory enlargement and paradoxical shrinkage of coronary arteries in presence of atherosclerotic lesions: an intracoronary ultrasound study based on multiple cross-section analysis per artery.

BACKGROUND: The aim of the study was to evaluate with intravascular ultrasound (IVUS) the incidence of compensatory enlargement and paradoxical shrinkage in 50 de novo coronary lesions, using two different approaches: 1) a single cross-section analysis and 2) a multiple cross-section analysis per artery. A 3-D IVUS system based on contour detection of lumen and plaque was applied (image acquisition speed: 0.5 mm/s, digitization rate: 5 images/s). In each cross section, we determined: 1) the lumen area (LA), 2) the external elastic membrane area (EEMA), 3) the plaque+media complex (p+m), 4) the relative EEMA = cross section EEMA/reference EEMA, 5) the relative p+m area = cross-section p+m area/reference p+m area, 6) the lumen area stenosis: 1-(cross-section LA/reference LA). In the single cross-section analysis, compensatory vessel enlargement was defined as narrowest EEMA > reference EEMA, and paradoxical vessel constriction as narrowest EEMA < reference EEMA. In the multiple cross-section analysis, compensatory vessel enlargement was defined as the presence of a significant positive correlation between relative EEMA and relative p+m area and paradoxical vessel constriction as a significant negative correlation between relative EEMA and lumen area stenosis. RESULTS: In the single cross-section analysis, compensatory vessel enlargement and paradoxical constriction occurred in 58 and 42% of cases respectively. The multiple cross-section per artery analysis showed compensatory vessel enlargement in 80% of cases and paradoxical constriction in 36% of cases and revealed the combination of compensatory enlargement with paradoxical constriction in 22% of the analyzed segments. CONCLUSIONS: Compensatory enlargement of coronary arteries was underestimated by the single cross-section analysis and was observed in 80% of cases when a multiple cross-section per artery analysis was applied. Paradoxical shrinkage was less common and often occurred in combination with compensatory enlargement within the same analyzed segment.