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P Merlet

Publications and source records attributed to P Merlet.

At least 19 recordsLinked to original sources

Cardiac abnormalities 15 years and more after adriamycin therapy in 229 childhood survivors of a solid tumour at the Institut Gustave Roussy.

The purpose of this paper was to determine the cardiac status in children 15 years or more after adriamycin therapy for a solid tumour. Of the 447 pts, 229 pts were fully studied and 218 were not. The following cardiac evaluations were proposed to all the 447 consecutive patients (pts): (1) cardiac Doppler US by one of two expert cardiologists; (2) cardiac rhythm and conduction abnormalities including 24-hour holter ECG; (3) (131)l-mlBG myocardial scintigraphy; (4) serum brain natriuretic peptide levels at rest; (5) an exercise test with VO(2) max measurement. The radiation doses delivered to 6 points in the heart were estimated for all patients who had received radiotherapy. Congestive heart failure was diagnosed in 24 of 229 (10%) evaluated pts, with a median interval of 15 years (0.3-24 years) from the first symptom after adriamycin treatment. Among the 205 remaining pts, 13 asymptomatic pts (6%) had severe (n=4) (FS<20%) or marked (n=9) (20< or =FS<25%) systolic dysfunction. In the 192 others, the median meridional end-systolic wall stress was 91 (53-135) and it exceeded 100 g cm(-2) in 52 pts. Using a Cox model, only the cumulative dose of adriamycin and the average radiation dose to the heart, were identified as risk factors for a pathological cardiac status. In conclusion, the risk of cardiac failure or severe abnormalities increases with adriamycin treatment, radiotherapy and time since treatment, even after a follow-up of 15 years or more. In our series, after an average follow-up of 18 years, 39% of the children had a severe cardiac dysfunction or major ventricular overload conditions. The risk increases with the dose of adriamycin and radiation received to the heart, without evidence for threshold.

Adolescent↗

[Aldosterone and its antagonists in heart failure].

THE ROLE OF ALDOSTERONE: Aldosterone is the key hormone in salt-water homeostasis. In heart failure, it participates in the appearance and maintenance of signs of congestion. Predominantly synthesised in the glomerular area of the cortico-adrenal glands, extra adrenal production areas have recently been identified notably in the brain, the heart and the large artery trunks. Aldosterone is activated in the cells by the intracellular mineral corticoid receptor. IN CARDIOVASCULAR-PATHOLOGIES: In chronic heart failure, patients treated with conversion enzyme inhibitor may escape from the renin-angiotensin blockade and this may lead to increased aldosterone plasma levels. This increase can induce not only vascular lesions and myocardial fibrosis but also renal and cerebral lesions. THE EFFECTS OF SPIRONOLACTONE: In patients with NYHA stage III or IV heart failure, addition of spironolactone to the treatment with conversion enzyme inhibitor, diuretic and/or digitalis leads to a reduction in morbidity and mortality, as demonstrated in the RALES study. The mechanisms by which spironolactone has a beneficial effect remain discussed. IN CLINICAL PRACTICE: The prescription of spironolactone is limited by hormonal side effects it provokes. IN THE FUTURE: Eplerenone, a new competitive aldosterone receptor antagonist that appears to be devoid of such side effects and which, at least experimentally may well have the same beneficial effects, is presently under clinical assessment.

Adrenergic beta-Antagonists↗

[Electromechanical mapping of myocardial ischemia in coronary occlusion in the pig].

The NOGA-Biosense catheter-based mapping technique has been well studied experimentally in infarction model. However, chronic myocardial ischemia with this new device has not been well explored. Thus, the aim of our study was to assess electromechanical changes in a pig aneroid constricor model. To achieved this aim, ten pigs were studied 21 days after the implantation of an aneroid constrictor around the circumflex artery. Coronary reserve assess by intracoronary Doppler flow wire was reduced in the ischemic lateral area (ILA) compared with the nonischemic zone (NIZ) (1.3 +/- 0.1 in the ILA vs. 2.3 +/- 0.2 in the NSZ; p < 0.01). TM echocardiography was used to evaluate myocardial regional contractility under basal condition and after stress induced by rapid atrial pacing. In stress state, the ischemic zone showed an impaired contractility compared with basal state (wall thickening, 32.7 +/- 7.4% vs. 59.7 +/- 8.6%; p < 0.05) whereas the non ischemic zone did not (53.8 +/- 7.6% vs. 60.8 +/- 10.1%; p = ns). Constrast echography showed a decrease in contrast intensity in subendocardium of the ila compared with the niz (46.2 +/- 16.6 vs. 99.2 +/- 35.6; p = 0.03) in pacing. Ventricular mapping quantified unipolar (UV). bipolar (BV) voltage potentials and endocardial local shortening (LLS) in 9 left ventricular regions. In basal state, electrical potentials were preserved in both zones (UV: 9.1 +/- 1.8 mV in the ischemic vs 11.3 +/- 3.6 mV in the non ischemic zone; p = ns; BV: 4.2 +/- 1.1 mV in the ILA vs. 3.9 +/- 1.5 mV; p = ns). In contrast, LLS was significantly lower in the ischemic compared with non ischemic zone (6.4 +/- 5.4% vs. 17.9 +/- 3.0%, p < 0.001). In conclusion, ventricular mapping with the NOGA-Biosense system can identify the ischemic myocardium. In this pig model, the association of a preserved electrical activity and an impaired mechanical activity characterizes the ischemic myocardium. These findings could be interesting in this model in regard of the new developments of the system in particular in the field of angiogenesis.

Animals↗

[Pathology and dental care in the context of cardiovascular conditions: myths, beliefs and realities].

The knowledge regarding the links between dental and cardiac affections are generally based on empirical concepts and lead to unjustified clinical practices. Infectious endocarditis (IE) is the principal cardiac diseases concerned with dental procedures. Although in France, the incidence of IE is stable, the incidence of oral bacteria at the origin of IE is diminishing. The risk of IE and thus the indication of antibioprophylaxis depend upon the subjacent cardiopathy and dental treatment. Antibioprophylaxis has to be very strict in patients with high or moderate risks of IE but is not necessary in low risk patients. In all cases, a good oral and dental hygiene and a regular dentist follow up are the most effective methods of preventing IE. Coronary artery disease and dental affections are associated because they present similar risk factors (i.e. smoking, excessive sugar consumption) and also because inflammation increases the risk of acute coronary syndrome. Today, dental cares are not contraindicated in patients with recent coronary syndrome if precise protocols are followed. Concerning the hemorrhagic risk during dental care in patients treated by anticoagulants and/or antithrombotics, dental cares and extractions are possible if INR or heparinemy are within the therapeutic limits and local haemostasis is meticulous. In addition, aspirin does not require to be stopped before minor dental treatments. Finally a better collaboration between dentists and cardiologists would allow an optimum management of patients with cardiac disease requiring dental cares.

Cardiovascular Diseases↗

[Future molecules in heart failure].

TODAY: The management of heart failure (HF) has considerably progressed over the last two decades. Treatment today relies on prevention and treatment of congestion (limited salt intake, diuretics, converting enzyme inhibitors) and limiting neurohormone stimulation (converting enzyme inhibitors +/- aldactone, beta-blockers). IN THE YEARS TO COME: Based on new concepts, several therapeutic strategies are interesting: blocking over vasoconstrictor systems which have not been taking into account; stimulation of vasodilator and natriuretic systems; modulation of cardiac remodelling; modulation of the immune and inflammatory systems; modification in intrinsic contractility; prevention of rhythm disorders. Among these differing strategies and molecules, it is not easy to predict those that will change the HF prognosis. In any event, their efficacy and safety remain to be demonstrated with large cohort randomised studies. THE PRINCIPLES: To reduce the number of drugs administered, two options appear particularly interesting: measurement of hormone levels (BNP) in order to adjust treatment and administration of molecules with greatest efficacy and safety profiles; limit cardiac remodelling by using new imaging techniques to detect it more precisely and select the molecule(s) exerting the required effect. To target the new molecules better, patients should be classified according to their etiology, stage and progressive profile of their disease, cardiac remodelling, expression of principle endocrine systems and pro-inflammatory cytokines, expression of inflammatory and immune systems and inherent genetic characteristics and response to treatment. This would permit the adaptation of treatment to each individual patient with heart failure.

Forecasting↗

Inflammation, cytokines and anti-inflammatory therapies in heart failure.

Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Certain categories in patients with dilated cardiomyopathy have shown the presence of humoral and cellular immunity activation suggesting a possible relation between myocarditis and dilated cardiomyopathy. Recent studies suggest a link between the circulating levels of cytokines (TNF alpha IL-1 et IL-6), the clinical status and prognostic. However, the mechanisms connecting heart failure and cytokine activation are unclear and the sites of cytokines production remain controversial. In the clinical setting, specific measurements of cytokines are not available. As tests of inflammation, erythrocyte sedimentation rate and C-reactive protein concentration appear to have interesting pronostic values. Current conventional therapy i.e. ACE inhibitors, type I angiotensin II antagonist and beta-blockers have shown some anti-cytokine properties. Recently, immunosuppressive therapies have shown their ability to improve symptoms and LV ejection in selected patients with dilated cardiomyopathy and clear sign of myocardium inflammation. Specific anti-cytokine therapy have been developed and showed interesting results in preliminary clinical studies. However large clinical trials testing this new therapy have been stoppel prematurely because of deterious effects.

Angiotensin-Converting Enzyme Inhibitors↗

Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy.

BACKGROUND: Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated. METHODS AND RESULTS: Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects. CONCLUSIONS: Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines.

3-Iodobenzylguanidine↗

Impaired cardiac adrenergic innervation assessed by MIBG imaging as a predictor of treatment response in childhood dilated cardiomyopathy.

OBJECTIVE: To evaluate the prognostic value of metaiodobenzylguanidine (MIBG) imaging in childhood cardiomyopathy. DESIGN: Prospective cohort study. SETTING: Tertiary referral centre. PATIENTS: 40 children (21 boys, 19 girls; mean (SD) age, 7.0 (5.6) years) with heart failure resulting from idiopathic dilated cardiomyopathy (n = 23) or various other disorders (n = 17). METHODS: At the initial examination, cardiac (123)I-MIBG uptake and release, circulating noradrenaline (norepinephrine) concentration, x ray cardiothoracic ratio, and echocardiographic variables were recorded. Cardiac MIBG uptake was obtained by measuring the heart to mediastinum activity ratio on the planar image obtained four hours after MIBG injection. MIBG washout rate was evaluated using relative decrease in cardiac activity measured at 20 minutes and four hours. Patients were treated with angiotensin converting enzyme inhibitors, diuretics, and digitalis, and were followed up for 12 (10) months. Fifteen patients did not respond to medical treatment (12 heart transplants; three deaths), and 25 did respond (improved or stable). RESULTS: Cardiac MIBG uptake was positively correlated with x ray cardiothoracic index (r = 0.55, p = 0.0008) and echocardiographic left ventricular fractional shortening (r = 0.68, p < 0.0001). Among all the clinical and laboratory variables tested, multivariate discriminant analysis showed that the only independent predictor of an unfavourable outcome was a low MIBG uptake (p < 0.001). Survival curves had a mean threshold value of 1.54 for MIBG uptake. CONCLUSIONS: Impaired cardiac adrenergic innervation is strongly related to adverse outcome in children with dilated cardiomyopathy, independently of the aetiology. MIBG imaging may help to stratify risk in such patients.

3-Iodobenzylguanidine↗

Clinical impact of (18)F-FDG PET in thyroid carcinoma patients with elevated thyroglobulin levels and negative (131)I scanning results after therapy.

UNLABELLED: 18F-FDG PET has been shown to effectively detect differentiated thyroid carcinoma (DTC) metastases with impaired iodine-trapping ability. This article evaluates the potential contribution of FDG PET in the follow-up of patients with differentiated thyroid carcinoma, elevated thyroglobulin (Tg) levels, and negative whole-body scan results obtained after high doses of (131)I. METHODS: We prospectively assessed the ability of FDG to detect metastases in 37 DTC patients who had undergone total thyroidectomy and radioactive ablation and presented with persistent disease, as assessed from elevated Tg levels and negative results of whole-body scans performed after therapeutic doses of (131)I. Additional conventional imaging procedures were performed to detect residual disease, and the patients were divided into 2 groups: group 1, with positive conventional imaging findings (n = 10), and group 2, with negative conventional imaging findings (n = 27). RESULTS: FDG PET showed positive findings in 28 patients and accurately localized tumor sites in 89% of them. In group 1, FDG PET confirmed 17 of 18 previously known tumor sites and detected 11 additional sites. In group 2, FDG PET findings were positive in 19 of 27 patients with no previously detected metastases. PET was effective for both low- and high-stage tumors. The FDG data led to a change in the clinical management of 29 of 37 patients with further surgical resection in 23 patients, 14 of whom achieved disease-free status, and external radiation therapy in 4 patients. CONCLUSION: FDG PET is able to detect metastases undetected by (131)I posttherapy whole-body scanning in patients with elevated Tg levels. It should be proposed as a first-line investigation in patients with persistent disease but negative findings on (131)I whole-body scans after treatment.

Adult↗

[Positron emission tomography in head and neck oncology: five cases].

FDG-PET (18-fluoro-desoxyglucose positron emission tomography) is a fonctionnal imaging method based on the high rate of glycolysis in different types of cancer-cells. We report the first five cases where FDG-PET was used in France for head and neck cancers. The results were analyzed on the basis of data reported to date in the literature, leading to a proposal for rational use of this diagnostic available in only a few centers in France. For primary assessment of cervicofacial carcinomas, different imaging techniques such as CT and MRI have improved tumor staging. Although 18-FDG-PET cannot replace these techniques used to monitor size and structural changes in tumors and lymph nodes, it will be helpful in following their metabolic activity. This diagnostic tool consequently is greatly helpful for detection and post-therapeutic evaluation of head and neck carcinomas and their recurrence. 18-FDG-PET is currently under evaluation as a tool for detecting cervical lymph nodes and early assessment of response to chemotherapy.

Fluorodeoxyglucose F18↗

Validation of myocardial perfusion reserve measurements using regularized factor images of H(2)(15)O dynamic PET scans.

UNLABELLED: The use of H(2)(15)O PET scans for the measurement of myocardial perfusion reserve (MPR) has been validated in both animal models and humans. Nevertheless, this protocol requires cumbersome acquisitions such as C(15)O inhalation or (18)F-FDG injection to obtain images suitable for determining myocardial regions of interest. Regularized factor analysis is an alternative method proposed to define myocardial contours directly from H(2)(15)O studies without any C(15)O or FDG scan. The study validates this method by comparing the MPR obtained by the regularized factor analysis with the coronary flow reserve (CFR) obtained by intracoronary Doppler as well as with the MPR obtained by an FDG acquisition. METHODS: Ten healthy volunteers and 10 patients with ischemic cardiopathy or idiopathic dilated cardiomyopathy were investigated. The CFR of patients was measured sonographically using a Doppler catheter tip placed into the proximal left anterior descending artery. The mean velocity was recorded at baseline and after dipyridamole administration. All subjects underwent PET imaging, including 2 H(2)(15)O myocardial perfusion studies at baseline and after dipyridamole infusion, followed by an FDG acquisition. Dynamic H(2)(15)O scans were processed by regularized factor analysis. Left ventricular cavity and anteroseptal myocardial regions of interest were drawn independently on regularized factor images and on FDG images. Myocardial blood flow (MBF) and MPR were estimated by fitting the H(2)(15)O time-activity curves with a compartmental model. RESULTS: In patients, no significant difference was observed among the 3 methods of measurement-Doppler CFR, 1.73 +/- 0.57; regularized factor analysis MPR, 1.71 +/- 0.68; FDG MPR, 1.83 +/- 0.49-using a Friedman 2-way ANOVA by ranks. MPR measured with the regularized factor images correlated significantly with CFR (y = 1.17x - 0.30; r = 0.97). In the global population, the regularized factor analysis MPR and FDG MPR correlated strongly (y = 0.99x; r = 0.93). Interoperator repeatability on regularized factor images was 0.126 mL/min/g for rest MBF, 0.38 mL/min/g for stress MBF, and 0.34 for MPR (19% of mean MPR). CONCLUSION: Regularized factor analysis provides well-defined myocardial images from H(2)(15)O dynamic scans, permitting an accurate and simple measurement of MPR. The method reduces exposure to radiation and examination time and lowers the cost of MPR protocols using a PET scanner.

Analysis of Variance↗

[Hospital mortality in cardiology. Analysis of deaths occurring in the Federation of Cardiology of a university hospital center].

The aim of this study was to examine the nature of cardiovascular deaths occurring in a University Hospital. All the hospital files of 1999 of the Federation of Cardiology of Henri Mondor Hospital, Creteil, of patients who died in the department or after transfer to the intensive care unit or cardiac surgery department, were analysed. Myocardial ischaemia was the leading cause of death, occurring either in the acute phase of transmural infarction or in patients with chronic cardiac failure. Deaths occurring during acute myocardial infarction were associated with late treatment and/or non-reperfusion of the culprit artery. The delay of diagnosis seemed to be secondary to late consultation or difficulty in diagnosis. This resulted in severe left ventricular dysfunction and, in a quarter of cases, mechanical complications. They led to the early death of the patients (2.9 +/- 3.5 days after admission). Campaigns of patient information and education of doctors who see these patients would seem to be the most appropriate approach to reduce the delay before hospital admission in order to reduce mortality related to myocardial infarction. Cardiac failure is a common cause of death in cardiology departments. The deaths of patients occurred after a long follow-up and several days after hospital admission (11 +/- 10 days). Optimisation of the treatment of cardiac failure, the investigation of ischaemic heart disease, the search for new therapeutic strategies of acute cardiac failure and information of patients about their disease, seem to be the principal measures to take to improve the poor prognosis of this disease.

Aged↗

[Fluorodeoxyglucose (FDO) positron emission tomography (PET) in testicular germ cell tumors in adults: preliminary French clinical evaluation, development of the technique and its clinical applications].

OBJECTIVES: Metabolic positron emission tomography (PET) is a new imaging modality for the detection of tumours, which uses fluorodeoxyglucose (FDG) to demonstrate increased carbohydrate metabolism of malignant cells. The management of testicular germ cell tumours in adults raises three clinical problems poorly resolved by conventional imaging techniques: identification of suspected recurrences in a context of elevated circulating serum markers, initial staging assessment after orchidectomy, evaluation of the response to treatment. MATERIAL AND METHODS: The authors report the data obtained in 16 patients (6 cases of seminoma and 10 cases of non seminomatous germ cell tumour [NSGCT]), investigated in the Frédéric-Joliot Department using a dedicated PET camera, 60 minutes after intravenous injection of 270 MBq of FDG. RESULTS: In 9 cases of assessment of elevated serum markers with no tumour identified by conventional examinations, PET demonstrated images likely to correspond to tumour sites in 7 patients (5 true-positives [TP] and 2 false-positives [FP] due to postoperative inflammatory changes). PET was negative in 2 out of 9 patients, in whom subsequent follow-up showed spontaneous but delayed return to normal of tumour markers. In 3 of the 4 cases of initial staging of the disease, PET excluded an extension suspected by conventional imaging and the 4th case was a FP for PET. In 3 cases of evaluation of the response to treatment, PET concluded on the absence of viable residual tumour mass, with a false-negative result in one case. CONCLUSIONS: These results are in line with those reported in the literature, which emphasize the diagnostic difficulties encountered in this disease. The significant contribution of FDG-PET should be confirmed by larger series of patients investigated by this new modality.

Adult↗

Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability.

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sudden deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42+/-12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36+/-0.26 versus 1.98+/-0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, without correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evaluate the extent of cardiac sympathetic denervation in FAP patients.

3-Iodobenzylguanidine↗

Cardiac metaiodobenzylguanidine uptake in patients with moderate chronic heart failure: relationship with peak oxygen uptake and prognosis.

OBJECTIVES: This prospective study was undertaken to correlate early and late metaiodobenzylguanidine (MIBG) cardiac uptake with cardiac hemodynamics and exercise capacity in patients with heart failure and to compare their prognostic values with that of peak oxygen uptake (VO2). BACKGROUND: The cardiac fixation of MIBG reflects presynaptic uptake and is reduced in heart failure. Whether it is related to exercise capacity and has better prognostic value than peak VO2 is unknown. METHODS: Ninety-three patients with heart failure (ejection fraction <45%) were studied with planar MIBG imaging, cardiopulmonary exercise tests and hemodynamics (n = 44). Early (20 min) and late (4 h) MIBG acquisition, as well as their ratio (washout, WO) were determined. Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses. RESULTS: Late cardiac MIBG uptake was reduced (131+/-20%, normal values 192+/-42%) and correlated with ejection fraction (r = 0.49), cardiac index (r = 0.40) and pulmonary wedge pressure (r = -0.35). There was a significant correlation between peak VO2 and MIBG uptake (r = 0.41, p < 0.0001). With a mean follow-up of 10+/-8 months, both late MIBG uptake (p = 0.04) and peak VO2 (p < 0.0001) were predictive of death or heart transplantation, but only peak VO2 emerged by multivariate analysis. Neither early MIBG uptake nor WO yielded significant insights beyond those provided by late MIBG uptake. CONCLUSIONS: Metaiodobenzylguanidine uptake has prognostic value in patients with wide ranges of heart failure, but peak VO2 remains the most powerful prognostic index.

3-Iodobenzylguanidine↗

Sympathetic nerve alterations assessed with 123I-MIBG in the failing human heart.

UNLABELLED: Norepinephrine (NE) reuptake function is impaired in heart failure and this may participate in myocyte hyperstimulation by the neurotransmitter. This alteration can be assessed by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. METHODS: To determine whether the impairment of neuronal NE reuptake was reversible after metoprolol therapy, we studied 18 patients (43+/-7 y) with idiopathic dilated cardiomyopathy who were stabilized at least for 3 mo with captopril and diuretics. Patients underwent, before and after 6 mo of therapy with metoprolol, measurements of radionuclide left ventricular ejection fraction (LVEF), maximal oxygen consumption and plasma NE concentration. The cardiac adrenergic innervation function was scintigraphically assessed with MIBG uptake and release measurements on the planar images obtained 20 min and 4 h after tracer injection. To evaluate whether metoprolol had a direct interaction with cardiac MIBG uptake and release, six normal subjects were studied before and after a 1-mo metoprolol intake. RESULTS: In controls, neither cardiac MIBG uptake and release nor circulating NE concentration changed after the 1-mo metoprolol intake. Conversely, after a 6-mo therapy with metoprolol, patients showed increased cardiac MIBG uptake (129%+/-10% versus 138%+/-17%; P = 0.009), unchanged cardiac MIBG release and decreased plasma NE concentration (0.930+/-412 versus 0.721+/-0.370 ng/mL; P = 0.02). In parallel, patients showed improved New York Heart Association class (2.44+/-0.51 versus 2.05+/-0.23; P = 0.004) and increased LVEF (20%+/-8% versus 27%+/-8%; P = 0.0005), whereas maximal oxygen uptake remained unchanged. CONCLUSION: Thus, a parallel improvement of myocardial NE reuptake and of hemodynamics was observed after a 6-mo metoprolol therapy, suggesting that such agents may be beneficial in heart failure by directly protecting the myocardium against excessive NE stimulation.

3-Iodobenzylguanidine↗

[Cardiac hypertrophy and coronary reserve in endurance athletes].

Impaired coronary reserve (CR) with angiographic coronary arteries has been demonstrated in patients with left ventricular hypertrophy (LVH) in response to valvular heart disease or hypertension. To determine if adaptive LVH induced by intensive training may alter myocardial blood flow (MBF) and CR, 8 highly trained endurance tri- athletes (29.6 +/- 4.0 yrs, with echographic LVH) were compared with 6 control subjects (33.0 +/- 7.9 yrs, with a normal echographic examination). Triathletes entered the study if they had a left ventricular mass >120 g/m2 at 2-D echocardiographic measurements (mean = 148.6 +/- 19.8 g/m2). MBF was assessed using positron emission tomography (PET) with H2O15. Subjects underwent an intravenous bolus of 17- 25 mCi of H2)15 at baseline and after intravenous infusion of 0.80 mg/kg of dipyridimole; H2O15 examination was followed by an F18-fluorodeoxyglucose (FDG) myocardial imaging. CR was determined as the ration of maximal to basal myocardial blood flow. In comparison with controls, triathletes with LVH showed normal MBF values (0.74 +/- 0.1 vs 0.8 +/- 0.2 ml/ml/min, p = 0.2), but an increased CR (3.8 +/- 0.7 vs 6.1 +/-1.9, p < 0.05). In contrast with other forms of LVH, CR is not altered in LVH due intense physical training. These results suggest that LVH due to intensive physical training is associated with an increase in coronary blood flow capacity.

Adult↗

Prognostic value of MIBG imaging in idiopathic dilated cardiomyopathy.

UNLABELLED: Alterations of cardiac sympathetic innervation are likely to contribute to fatal outcomes in patients with heart failure. These alterations can be evaluated noninvasively by 123I-metaiodoben-zylguanidine (MIBG) imaging. METHODS: The hypothesis that impaired cardiac sympathetic innervation, as assessed using MIBG imaging, is related to adverse outcomes was tested in 112 patients with heart failure resulting from idiopathic cardiomyopathy. Main inclusion criteria were New York Heart Association classes II-IV and radionuclide left ventricular ejection fraction (LVEF) < 40%. Patients were assessed for cardiac MIBG uptake, circulating norepinephrine concentration, LVEF, peak Vo2, x-ray cardiothoracic ratio, M-mode echographic end-diastolic diameter and right-sided heart catheterization parameters. RESULTS: During a mean follow-up of 27 +/- 20 mo, 19 patients had transplants, 25 died of cardiac death (8 sudden deaths), 2 died of noncardiac death and 66 survived without transplantation. The only independent predictors for mortality were low MIBG uptake (P < 0.001) and LVEF (P = 0.02) when using multivariate discriminant analysis. Moreover, MIBG uptake (P < 0.001) and circulating norepinephrine concentration (P = 0.001) were the only independent predictors for life duration when using multivariate life table analysis. CONCLUSION: Impaired cardiac adrenergic innervation as assessed by MIBG imaging is strongly related to mortality. MIBG imaging may help risk stratify patients with heart failure resulting from idiopathic dilated cardiomyopathy.

3-Iodobenzylguanidine↗