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Abstract Background Hypertrophic Cardiomyopathy (HCM) is a genetically heterogeneous disease. One specific mutation in the MYBPC3 gene is highly prevalent in center east of France giving an opportunity to define the clinical profile of this specific mutation. Methods HCM probands were screened for mutation in the MYH7, MYBPC3, TNNT2 and TNNI3 genes. Carriers of the MYBPC3 IVS20-2A>G mutation were genotyped with 8 microsatellites flanking this gene. The age of this MYBPC3 mutation was inferred with the software ESTIAGE. The age at first symptom, diagnosis, first complication, first severe complication and the rate of sudden death were compared between carriers of the IVS20-2 mutation (group A) and carriers of all other mutations (group B) using time to event curves and log rank test. Results Out of 107 HCM probands, 45 had a single heterozygous mutation in one of the 4 tested sarcomeric genes including 9 patients with the MYBPC3 IVS20-2A>G mutation. The IVS20-2 mutation in these 9 patients and their 25 mutation carrier relatives was embedded in a common haplotype defined after genotyping 4 polymorphic markers on each side of the MYBPC3 gene. This result supports the hypothesis of a common ancestor. Furthermore, we evaluated that the mutation occurred about 47 generations ago, approximately at the 10th century. We then compared the clinical profile of the IVS20-2 mutation carriers (group A) and the carriers of all other mutations (group B). Age at onset of symptoms was similar in the 34 group A cases and the 73 group B cases but group A cases were diagnosed on average 15 years later (log rank test p = 0.022). Age of first complication and first severe complication was delayed in group A vs group B cases but the prevalence of sudden death and age at death was similar in both groups. Conclusion A founder mutation arising at about the 10th century in the MYBPC3 gene accounts for 8.4% of all HCM in center east France and results in a cardiomyopathy starting late and evolving slowly but with an apparent risk of sudden death similar to other sarcomeric mutations.

Cardiac functional imaging focuses on three variables which complement each other: coronary perfusion reserve (during stress or after maximal vasodilation), myocardial viability (at cellular level) and ventricular contraction (endocardial motion or myocardial thickening). A combination of abnormal findings (location, size and severity) helps to characterise the myocardium in terms of normal, ischaemic, stunned, hibernating or necrosis. This functional information is then used to validate the morphological images of coronary lesions as seen on angiography, to assess the significance of a stenosis, to identify the culprit vessel in cases of multivessel disease, and to delineate the area at risk. "Non-invasive" techniques should no longer be considered only as screening methods with more sophisticated investigations in view, but should replace them at every step of patient management: at the time of diagnosis, with a "positive/negative" bayesian approach, before a therapeutic decision and during follow-up, especially when considering the prognosis of patients and risk stratification when the quantitation of functional abnormalities are major determinants.

Background: Transmural myocardial contractile performance is nonuniform across the different layers of the left ventricular wall. We evaluated the accuracy of color M-mode tissue Doppler imaging (TDI) to assess the transmural distribution of myocardial velocities and to quantify the severity of dysfunction induced by acute ischemia and reperfusion in the inner and outer myocardial layers., Methods and Results: Thirteen open-chest dogs underwent 15 minutes of left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion. M-mode TDI was obtained from an epicardial short-axis view. Systolic velocities were calculated within endocardium and epicardium of the anterior and posterior walls. Regional myocardial blood flow was assessed by radioactive microspheres. Segment shortening was measured by sonomicrometry in endocardium and epicardium of both the anterior and posterior walls. At baseline, endocardial velocities were higher than epicardial velocities, resulting in an inner/outer myocardial velocity gradient. Ischemia caused a significant and comparable reduction in endocardial and epicardial systolic velocities in the anterior wall with the disappearance of the velocity gradient. Systolic velocities significantly correlated with segment shortening in both endocardium and epicardium during ischemia and reperfusion. In the first minutes after reflow, endocardial velocities showed a greater improvement than epicardial velocities, and the velocity gradient resumed although to a limited extent, indicative of stunning., Conclusions: TDI is an accurate method to assess the nonuniformity of transmural velocities and may be a promising new tool for quantifying ischemia-induced regional myocardial dysfunction.

The patients who have only single vessel disease of the right coronary artery have an excellent prognosis, unaffected by surgery. The object of this study was to evaluate the long-term prognosis of these patients after transluminal coronary angioplasty. The criteria of analysis were survival, anginal symptoms, quality of life and ergometric parameters. Two hundred and forty eight patients with an isolated lesion of the right coronary artery who underwent angioplasty were reassessed 39.6 +/- 22 months after angioplasty. The primary success rate was 89.9% with 5.2% of severe complications during the hospital period (myocardial infarction, bypass surgery, coronary angiography +/- angioplasty). The actuarial global and cardiac survival rates at 7 years were 88.4 and 96.2% respectively with no difference between the success and failure groups. The eight cardiovascular deaths and thirteen myocardial infarctions which were observed in the long-term were all in the successful angioplasty group. From the symptomatic viewpoint, 76% of the population became asymptomatic. The same results were observed in terms of quality of life with 58% of patients estimating it to be good in correlation with anginal status. The comparison of ergometric tests showed a significant gain in performance in 67% of patients. The authors conclude that the results suggest that angioplasty in single vessel disease of the right coronary artery provides a significant symptomatic and ergometric benefit but that it is impossible to assess the eventual benefits in terms of survival which would have needed a group of similar patients assessed under anti-ischaemic treatment and taking into consideration the recent innovations (stents, statins).

Background: Quantification of regional myocardial function is a major unresolved issue in cardiology. We evaluated the accuracy of pulsed Doppler tissue imaging (DTI), a new echocardiographic technique, to quantify regional myocardial dysfunction induced by acute ischemia and reperfusion., Methods and Results: In nine open-chest anesthetized pigs, various degrees of regional wall motion abnormalities were induced by graded reduction of left anterior descending coronary artery (LAD) blood flow. Pulsed Doppler tissue imaging was performed from an epicardial apical four-chamber view with the sample placed within the middle part of the septal wall. Peak septal velocities were calculated during systole, isovolumic relaxation, and early and late diastole. Regional myocardial blood flow and systolic and diastolic dysfunctions were assessed by radioactive microspheres and ultrasonic crystals, respectively. Ischemia resulted in a significant rapid reduction of systolic velocities and an early decrease in the ratio of early to late diastolic velocities. Both changes were detected by pulsed DTI within 5 seconds of coronary artery occlusion. The decrease in systolic velocity significantly correlated with both systolic shortening (r=.90, P<.0001) and regional myocardial blood flow (r=.96, P<.0001) during reduction of LAD blood flow., Conclusions: These results suggest that DTI may be a promising new tool for the quantification of ischemia-induced regional myocardial dysfunction.

The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methylhexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and to evaluate its contribution compared with the 201Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection 201Tl imaging, rest MIHA imaging and glucose-loaded FDG imaging were performed in 22 patients with recent myocardial infarction. Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum uptake on stress 201Tl imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a) 201Tl activity during exercise, redistribution and reinjection and (b) MIHA uptake, using the two FDG thresholds most commonly considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that 201Tl reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85 and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively; P<0.05 vs other tests). The global predictive values of MIHA and 201Tl reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments were considered, 201Tl reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold, P<0.05 vs 201Tl reinjection). In all circumstances, MIHA was less specific than 201Tl reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA accurately detects the persistence of metabolic viability, but is not superior to 201Tl.

In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and a stress ECG were performed in 34 patients referred for diagnostic or assessment coronary angiography. Dobutamine, administered in 3-minute stages from 5 to 30 micrograms/kg/min, was well tolerated. The anti-ischaemic treatment was continued in 26 patients before dobutamine echocardiography and in 15 patients before the stress ECG. The electrocardiographic, echocardiographic and angiographic documents were each analysed by 2 independent observers. Dobutamine echocardiography was considered to be positive in the presence of the development of a new abnormality of segmental kinetics or when abnormality of segmental kinetics was identified outside of the territory of infarction. With reference to coronary angiography, the sensitivity of stress ECG and dobutamine echocardiography was 46% and 42%, respectively, and the specificity was 75% and 88%, respectively; the sensitivity of each test was low, probably because of fake tests. The combination of the two tests improved the sensitivity (69%) without altering the specificity (75%). Dobutamine echocardiography could usefully complete a negative stress ICG whenever a false-negative result is suspected to avoir wrongly reassuring some patients and to allow appropriate management.

Long QT syndrome (LQT) is a genetically heterogeneous inherited disorder that causes sudden death from cardiac arrhythmia. Four loci have been mapped to chromosomes 3, 4, 7 and 11 and three specific mutated genes for LQT syndrome have been identified. LQT2 results from mutations in the human ether-a-gogo-related gene, HERG, a cardiac potassium channel, whose protein product likely underlies Ikd the rapidly activating delayed rectifier current. By SSCP analysis and direct sequencing, we determined a new missense mutation in the HERG coding sequence, a G to A transition at position 1681 resulting in the substitution of threonine for a highly conserved alanine at codon 561. This mutation, Ala561Thr, in the coding sequence of the fifth membrane-spanning domain (S5) of the HERG protein seems to convey a risk of cardiac events in affected family members. In addition to a prolonged T wave of low amplitude on the surface ECG, a distinctive biphasic T-wave pattern was found in the left precordial leads of all affected subjects with the Ala561Thr mutation regardless of age, gender and beta blocking therapy.

With the use of[11C]acetate, positron emission tomography (PET) permits exploration of myocardial blood flow (MBF) and oxidative metabolism (MVo2) coupling. PET imaging was performed at rest and under dobutamine infusion in 8 normal subjects and 10 coronary artery disease (CAD) patients with significant single-vessel left anterior descending (LAD) stenosis (> 70%) and normal regional left contractile function at rest. Resting MBF and MVo2 were similar in remote and LAD regions of normal subjects and patients. During dobutamine infusion, MBF and myocardial flow reserve were lower in LAD regions of patients compared with remote regions (MBF: 1.49 +/- 0.42 and 2.06 +/- 0.57 ml.g-1.min-1, P < 0.01; reserve: 1.73 +/- 0.59 and 2.14 +/- 0.47, P < 0.01, respectively), whereas MVo2 expressed as kmono (an index of MVo2) and metabolic reserve were similar (kmono: 0.106 +/- 0.021 vs. 0.107 +/- 0.017 min-1; reserve: 1.88 +/- 0.32 vs. 1.98 +/- 0.37, respectively). This is the first human study showing that, in normal contractile regions at rest but perfused by stenosed artery, a disparate rise in MVo2 relative to the rise in myocardial perfusion occurs during increased cardiac work induced by dobutamine. This flow-metabolism uncoupling probably reflects an increase in O2 extraction.

Following a case of torsades de pointe (TDP) after the injection of droperidol (D), the authors studied the electrocardiographic variations caused by the drug. Fifty five unselected patients under the same conditions (general anesthesia) were given D (0.25 mg/kg IV). Significant prolongation of the QT interval was seen in 70% of cases by the end of the first minute. QT interval and the ratio of QTm (measured) over QTt increased from 387 +/- 34 ms to 423 +/- 37 ms (p less than 0.0001) and from 1.06 +/- 0.08 to 1.28 +/- 0.1 (p less than 0.001) respectively. These changes could favourise the onset of TDP. Although exceptional in terms of the extensive use of the neuroleptic in question, this possibility indicates the need for monitoring of the duration of QT before and during treatment with droperidol and for prescription of the drug to be avoided in circumstances known to be propitious to this arrhythmia (bradycardia, hypokalemia, anti-arrhythmic drugs).

A retrospective study of Holter monitoring of 250 patients referred for syncope and short spells of dizziness suspected of being cardiac in origin was undertaken to assess the diagnostic value of the investigation. The arrhythmias observed were classified in 3 groups, significant, suspect and physiological with respect to their true or potential severity and to previously reported results of Holter monitoring in healthy subjects. The following arrhythmias were classified as significant: supraventricular tachycardia with a ventricular rate greater than or equal to 200 bpm; sustained ventricular tachycardia (greater than 30 s and greater than or equal to 150 bpm), bradycardia (less than bpm), sinus arrest (waking greater than 2 s sleeping greater than or equal to 6 s), complete AV block with wide QRS complexes and pacemaker dysfunction. The following arrhythmias were classified as suspect: paroxysmal supraventricular tachycardia with a ventricular rate less than 200 bpm, salvos of ventricular tachycardia (120 greater than 150 bpm); R/T phenomenon and doublets (greater than or equal to 50/24 hours), sinus arrest of 2 to 6 seconds during sleep, complete AV block with narrow QRS complexes or second degree Mobitz II block. This classification led to a diagnosis of certitude in 20 patients (5.7%) with significant arrhythmias concomitant with syncope or a minor form in only 5 cases, supraventricular tachycardia (4 cases), ventricular tachycardia (4 cases), AV block (5 cases), sinus arrest (3 cases), pacemaker dysfunction (4 cases); a diagnosis of presumption in 74 patients (21.1%) with suspect arrhythmias in the absence of syncope or minor equivalent.(ABSTRACT TRUNCATED AT 250 WORDS)

A hydatid cyst of the left ventricular posterior wall was diagnosed by 2D echocardiography in a 36 year old North African patient presenting with exertional dyspnoea and atypical chest pain. Clinical examination was negative but the surface ECG showed inverted T-waves in the infero-lateral leads. Postero-anterior and lateral chest X rays were initially interpreted as normal but 2D echocardiography immediately revealed a cystic cardiac tumour which very probably was hydatid, given the patient's origin. Thorough investigation showed no other localisations and hydatid serology was also negative. Left ventricular and selective coronary angiography were performed to determine the vascular relationships of the cyst: ablation was carried out under cardiopulmonary bypass and pathological examination confirmed the diagnosis of hydatid disease.

Two cases of pulmonary embolism accompanied by syncope in patients with pre-existing left bundle branch block are reported. Contrary to classical descriptions, the syncopes in these two patients could not be ascribed to cardiovascular collapse, but several arguments (such as the clinical features of the syncope and its coexistence in one case with ECG evidence of complete atrio-ventricular dissociation) were in favour of a paroxysmal disorder of conduction. Right bundle branch block is known to be common in pulmonary embolism and may even be more frequent in patients with left bundle branch block. In such cases, sudden and transient arrest of conduction in the right bundle would complete the left bundle branch block, thus accounting for a paroxysmal atrio-ventricular block.

Four personal cases with histological examination of the liver and a review of 70 cases collected from the literature have enabled the authors to develop the diagnostic problems involved in acute cardiac liver. An accurate diagnosis of this condition, which consists of acute hepatic cytolysis on a background of heart failure, can only be based on its course and/or on the presence of histological changes in the liver.

Reversible cardiocirculatory arrest was observed during orthopaedic treatment of a digital dislocation in a 37 year old female patient. Cardiological studies showed a prolonged QT interval (0.6 s) in the patient and her daughter, associated with hypokalemia (3.4 mmol) in the former. The diagnosis suggested was that of Romano-Ward's syndrome. Preparation and choice of anaesthesia are discussed.

An evaluation of the incidence of cardiac lesions in sarcoidosis was conducted in a group of patients with progressive pulmonary signs of the disease. Five non-invasive methods: echocardiogram, ECG, Holter, effort ECG, and thallium scintigraphy were employed on a routine basis; 31 patients were investigated by all procedures, scintigraphy being performed in all 37 cases. First degree auriculoventricular block was detected in only one case, this being compatible with cardiac sarcoidosis, though the possibility of a congenital lesion could not be excluded. The ECG remains an essential investigation among those employed, other examinations not supplying superior data. Scintigraphy appears to be of positive value, as faults in localized uptake were demonstrated in 17 p. cent of cases, these possibly corresponding to intramyocardial granulomas.

Although Q wave and non-Q wave MI are often referred to as "transmural" and "nontransmural," there is no anatomic evidence to justify this distinction. Nevertheless, a distinction is important, because the two entities have a different prognosis. At the present time, between 25% and 35% of MIs are non-Q wave. They are frequently observed in patients with previous coronary events. They occur in a relatively older population and involve a slightly higher proportion of women than do Q wave MIs. The degree of cardiac damage is less, reflected by a smaller rise in enzyme level and less impairment of left ventricular ejection fraction; early reperfusion may occur, after spontaneous thrombolysis or resolution of coronary spasm. The immediate mortality rate is half that of Q wave MI but identical in the long term. Reinfarction and angina are more frequent because of a peri-infarction zone of ischemia maintained by a high-grade coronary stenosis and inadequate collateral circulation. Early characterization of those MIs likely to progress is important. Diltiazem seems effective in this context if given between 24 and 72 hours of the onset of the event. Other therapeutic approaches need further assessment.