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MYBPC3 is the most frequently mutated gene in hypertrophic cardiomyopathy (HCM). Several loss-of-function founder variants have been reported in MYBPC3 from various geographic regions, altogether suggestive of a modest or absent effect of these variants on reproductive fitness. One of them, a MYBPC3 splice variant, NM_000256.3:c.3330+2T > G, was first described in homozygous state in newborns presenting with a severe, recessive form of HCM among the Amish population and was later associated with adult-onset dominant HCM in heterozygous carriers. We here report this splice variant in heterozygous state in eight unrelated Swiss families with HCM, making it the most prevalent cardiomyopathy variant in western Switzerland. This variant was identified in patients using targeted (n = 5) or full-genome sequencing (n = 3). Given the prevalence of this variant in the Old Order Amish, Mennonites and Swiss populations, and given that both Amish and Mennonites founders originated from the Bern Canton in Switzerland, the MYBPC3, NM_000256.3:c.3330+2T > G variant appears to be of Swiss origin. Neighboring regions that hosted the first Amish settlements (Alsace, South Germany) should be on the lookout for that variant. The existence of MYBPC3 founder variants in different populations suggests that individuals with early-onset clinical disease may be the tip of the iceberg of a much larger number of asymptomatic carriers. Alternatively, reproductive fitness could even be slightly increased in some variant carriers to compensate for the reduction of fitness in the more severely affected ones, but this remains to be investigated., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: To quantify mitral regurgitation (MR) with CMR, the regurgitant volume can be calculated as the difference between the left ventricular (LV) stroke volume (SV) measured with the Simpson's method and the reference SV, i.e. the right ventricular SV (RVSV) in patients without tricuspid regurgitation. However, for patients with prominent mitral valve prolapse (MVP), the Simpson's method may underestimate the LV end-systolic volume (LVESV) as it only considers the volume located between the apex and the mitral annulus, and neglects the ventricular volume that is displaced into the left atrium but contained within the prolapsed mitral leaflets at end systole. This may lead to an underestimation of LVESV, and resulting an over-estimation of LVSV, and an over-estimation of mitral regurgitation. The aim of the present study was to assess the impact of prominent MVP on MR quantification by CMR., Methods: In patients with MVP (and no more than trace tricuspid regurgitation) MR was quantified by calculating the regurgitant volume as the difference between LVSV and RVSV. LVSV uncorr was calculated conventionally as LV end-diastolic (LVEDV) minus LVESV. A corrected LVESV corr was calculated as the LVESV plus the prolapsed volume, i.e. the volume between the mitral annulus and the prolapsing mitral leaflets. The 2 methods were compared with respect to the MR grading. MR grades were defined as absent or trace, mild (5-29% regurgitant fraction (RF)), moderate (30-49% RF), or severe (≥50% RF)., Results: In 35 patients (44.0 ± 23.0y, 14 males, 20 patients with MR) the prolapsed volume was 16.5 ± 8.7 ml. The 2 methods were concordant in only 12 (34%) patients, as the uncorrected method indicated a 1-grade higher MR severity in 23 (66%) patients. For the uncorrected/corrected method, the distribution of the MR grades as absent-trace (0 vs 11, respectively), mild (20 vs 18, respectively), moderate (11 vs 5, respectively), and severe (4 vs 1, respectively) was significantly different (p < 0.001). In the subgroup without MR, LVSV corr was not significantly different from RVSV (difference: 2.5 ± 4.7 ml, p = 0.11 vs 0) while a systematic overestimation was observed with LVSV uncorr (difference: 16.9 ± 9.1 ml, p = 0.0007 vs 0). Also, RVSV was highly correlated with aortic forward flow (n = 24, R 2  = 0.97, p < 0.001)., Conclusion: For patients with severe bileaflet prolapse, the correction of the LVSV for the prolapse volume is suggested as it modified the assessment of MR severity by one grade in a large portion of patients.

Multidisciplinary cardiogenetic consulting offers a global clinical approach to patients suffering from channelopathies or hereditary cardiomyopathies. Mutation is discovered in around 50 % of the cases. Several experts are working together to bring probands and their families useful and necessary informations to help them understanding causes, consequences and support of their disease. This approach is developped in close collaboration with the treating physician., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Fenestrated aortic valve is a frequent condition which is, for most of the time, asymptomatic and generally has no influence on aortic valve competence. However, aortic valve regurgitation could occur, especially in the case of fibrous strand rupture. In this situation, acute aortic regurgitation is poorly tolerated and requires urgent surgical correction. Herein is presented the case of a 70-year-old patient who was admitted as an emergency for acute heart failure after coital exertion. Echocardiography revealed severe acute aortic regurgitation due to leaflet prolapse. Intraoperative inspection of the valve showed a strand rupture of the isolated fenestration.

Mitral regurgitation (MR) is the most frequent valvular disease in industrialised countries. MR is classified as primary (mostly degenerative with valve prolapse) or secondary (mainly due to underlying ischemic heart disease resulting in deformation of the valve structure). Surgical repair represents the optimal treatment for severe primary MR, whereas the benefits of surgical correction of secondary MR are controversial. Over the past few years, transcatheter techniques have been developed to treat MR, such as the percutaneous edge-to-edge procedure (MitraClip). These approaches represent a novel therapeutic choice for patients judged inoperable by the "heart team". This review article aims to summarize the principles of MR assessment and discuss current therapeutic options for severe MR, taking into account the latest advances in the field.

Urgent reoperative transapical aortic valve-in-valve has never been proposed as a treatment option in case of a failed transcatheter aortic valve implantation (TAVI) or in case of worsening of an existing paravalvular leak, if this complication occurs right after, or a few days after, the primary transapical aortic valve implantation. Experienced surgeons should argue that after a transapical TAVI, the apex is damaged and fragile, with a high risk of irreparable ventricular tears and life-threatening bleeding if a second transapical procedure is scheduled during the acute phase. Nevertheless, if the patient is inoperable and the vascular status, including the ascending aorta, limits alternative accesses, the urgent reoperative transapical valve-in-valve becomes an alternative. We illustrate, for the first time ever, our experience with an 81-year old female patient who underwent a transapical (TA) TAVI with a Sapien XT 23 mm. The day after the procedure, the patient haemodynamically worsened in combination with a worsening of a known (grade 1-2) paravalvular leak. Thus, on postoperative day two, an urgent transapical valve-in-valve was performed, and a second Sapien XT 23 mm was placed, with an excellent haemodynamic result and absence of leak. The redo apical access did not appear very complicated and the postoperative recovery was uneventful., (© The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The results of several large multicenter CMR studies were reported in 2012, thus, constantly corroborating the evidence on CMR performance. In this review, we present results of the MR-IMPACT programme and the CE-MARC study, which demonstrated the superiority of perfusion-CMR over gated SPECT for the workup of suspected CAD, the currently available data from the European CMR registry, comprising almost 30,000 patients from 57 participating centers in 15 European countries, and finally, the results of the Advisa-MRI study, which documented the safety of a MRI-compatible pacemaker system. These large trials and others set the basis for the recommendations in the new European guidelines on heart failure to use CMR as a first line method if echocardiographic quality is inadequate or the etiology of heart failure is unclear.

Acute myocarditis was until recently one of the most difficult diagnoses in cardiology. The spectrum of signs and symptoms is very wide, the usual non-invasive tests lack specificity and the myocardial biopsy is only performed in a minority of cases to confirm the diagnosis. Due to its unique ability to directly image myocardial necrosis, fibrosis and oedema, cardiac magnetic resonance (CMR) is now considered the primary tool for noninvasive assessment of patients with suspected myocarditis. CMR is also useful for monitoring disease activity under treatment. Myocarditis has been associated with the development of dilated cardiomyopathy; CMR could play a role in the follow-up of such cases to detect the progression toward a dilatative phenotype. Precise mapping of myocardial lesions with cardiac MRI is invaluable to guide myocardial biopsy and increase its diagnostic yield by improving sensitivity.

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease (1/500) and the most common cause of sudden cardiac death in young people. Pathogenic mutation detection of HCM is having a growing impact on the medical management of patients and their families. However, the remarkable genetic and allelic heterogeneity makes molecular analysis by conventional methods very time-consuming, expensive and difficult to realise in a routine diagnostic molecular laboratory., Method and Results: The authors used their custom DNA resequencing array which interrogates all possible single-nucleotide variants on both strands of all exons (n=160), splice sites and 5'-untranslated region of 12 HCM genes (27 000 nucleotides). The results for 122 unrelated patients with HCM are presented. Thirty-three known or novel potentially pathogenic heterozygous single-nucleotide variants were identified in 38 patients (31%) in genes MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL3 and ACTC1., Conclusions: Although next-generation sequencing will replace all large-scale sequencing platforms for inherited cardiac disorders in the near future, this HCM resequencing array is currently the most rapid, cost-effective and reasonably efficient technology for first-tier mutation screening of HCM in clinical practice. Because of its design, the array is also an appropriate tool for initial screening of other inherited forms of cardiomyopathy.

Background: An elevated early (E) to late (A) diastolic filling velocities ratio, typically seen in advanced diastolic dysfunction, has also been observed after cardioversion of atrial fibrillation as a consequence of the depressed left atrial (LA) contractility. We hypothesized that the impaired LA contractile function demonstrated after orthotopic cardiac transplantation (OCT) could also lead to this "pseudorestrictive" pattern., Method: E/A ratio related to the tissue Doppler early mitral annular velocity (Ea) as preload-independent index of LV relaxation was evaluated in all consecutive OCT patients between 2005 and 2007., Results: The study population comprised 48 patients 97 ± 77 months after OCT. Thirty-two patients (67%) had an E/A ratio > 2. LV systolic function and myocardial relaxation assessed by the Ea velocity were similar compared to patients with normal ratio (61 ± 6% vs. 60 ± 12%, P = 0.854 and 15 ± 4 cm/s vs. 14 ± 3 cm/s, r = 0.15, P = 0.323, respectively). On the other hand, the proportion of the recipient and donor LA cuffs as estimated by the recipient/global LA area ratio and the LA emptying fraction significantly correlated with the E/A ratio (r = 0.40, P = 0.005 and r =-0.33, P = 0.022, respectively)., Conclusion: Our study shows that there is a high prevalence of elevated E/A ratio after standard OCT which seems mainly related to reduced LA contractility. Recognition of this "pseudorestrictive" pattern may avoid misdiagnosis of diastolic dysfunction., (© 2011, Wiley Periodicals, Inc.)

The present review provides a selected choice of clinical research in the field of interventional cardiology, electrophysiology and cardiac imaging. We also focused on the new guidelines published by the European society of cardiology in 2010 (revascularization, atrial fibrillation and device therapy in heart failure).

Aims: To evaluate thoracic aortic dilation in patients with Fabry disease (FD)., Methods and Results: A cohort of 106 patients with FD (52 males; 54 females) from three European centres were studied. The diameter of the thoracic aorta was assessed at three levels (sinus of Valsalva, ascending aorta, and descending aorta) using echocardiograms and cardiovascular magnetic resonance imaging. Aortic dilation at the sinus of Valsalva was found in 32.7% of males and 5.6% of females; aneurysms were present in 9.6% of males and 1.9% of females. No aortic dilation was observed in the descending aorta. There was no correlation between aortic diameter at the sinus of Valsalva and cardiovascular risk factors., Conclusion: Fabry disease should be considered as a cardiovascular disease that affects the heart and arterial vasculature, including the thoracic aorta. Thus, patients with FD should be closely monitored for the presence, and possible progression and complications of aortic dilation., Clinical Trial Registration: Protocol 101/01. Ethics committee, Faculty of Medicine, Lausanne.

Cardiovascular magnetic resonance (CMR) is a rapidly emerging non-invasive imaging technique free of X-Ray and offers higher spatial resolution than alternative forms of cardiac imaging for the assessment of left ventricular (LV) anatomy, function, and viability due to the unique capability of myocardial tissue characterization after gadolinium-chelates contrast administration. This imaging technique has clinical utility over a broad spectrum of heart diseases: ranging from ischaemic to non ischaemic aetiologies. Cardiomyopathies (CMP) are a heterogeneous group of diseases of the myocardium associated with architectural abnormalities and mechanical dysfunction. CMR can help excluding coronary artery disease and can provide positive diagnostic features for several CMP resulted in better diagnosis and management, Leading to improvements in mortality.

The non-invasive evaluation of myocardial ischemia is a priority in cardiology. The preferred initial non-invasive test is exercise ECG, because of its high accessibility and its low cost. Stress radionuclide myocardial perfusion imaging or stress echocardiography are now routinely performed, and new non-invasive techniques such as perfusion-MRI, dobutamine stress-MRI or 82rubidium perfusion PET have recently gained acceptance in clinical practice. In the same time, an increasing attention has been accorded to the concept of myocardial viability in the decisional processes in case of ischemic heart failure. In this indication, MRI with late enhancement after intravenous injection of gadolinium and 18F-FDG PET showed an excellent diagnostic accuracy. This article will present these new imaging modalities and their accepted indications.

Echocardiography is the preferred initial noninvasive test to assess heart muscle and heart valves. Cardiac MRI has a unique capacity to directly characterise myocardial tissue with specific imaging sequences and late enhancement pattern after gadolinium injection, and has a specific role in the diagnosis of cardiomyopathies. In valvular heart diseases, cardiac MRI precisely measures the severity of aortic or pulmonary regurgitation. In pericardial heart diseases, and specifically when constrictive pericarditis is suspected, cardiac MRI and/or CT are useful to look for pericardial thickening. Cardiac CT and MRI are very rapidly developing techniques in cardiology; the use of these expensive techniques must follow the currently accepted indications in order to be integrated in a rational diagnosis process in clinical practice.

Echocardiography is the preferred initial test to assess cardiac morphology and ventricular function. Cardiac MRI enables an optimal visualisation of heart muscle without contrast injection, and precise measurement of the ventricular volumes and systolic function. It is therefore an ideal test for patients with poor echocardiographic windows or for the specific evaluation of right heart chambers. Heart CT also remarkably images heart muscle and precisely measures ventricular systolic function after intravenous injection of iodinated contrast. Coronary CT may also, in selected cases, avoid the need for diagnostic coronary angiography. Although very accurate, these imaging modalities are expensive and may be contra-indicated for a particular patient. Their use in clinical practice has to follow the accepted guidelines.

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

The beneficial effect of cardiac resynchronization therapy has been demonstrated in large clinical trials. However, on an individual basis 20% to 30% of patients receiving this therapy will lack improvement or even deteriorate. A better selection of patients to predict response to cardiac resynchronization therapy is therefore needed. Echocardiographic studies have clearly demonstrated that the presence of intra-ventricular dyssynchrony is an important factor determining response to resynchronization therapy, whereas interventricular dyssynchrony appears to be of less importance. Of the different echocardiographic approaches aimed at prediction of response to resynchronization therapy, literature suggests that tissue Doppler imaging may represent the best method. Ongoing research trials will further define the role of other new bi- or three-dimensional echocardiographic tools in the clinical management of patients with heart failure.

It has been suggested that the shape of the normalized time-varying elastance curve [E(n)(t(n))] is conserved in different cardiac pathologies. We hypothesize, however, that the E(n)(t(n)) differs quantitatively after myocardial infarction (MI). Sprague-Dawley rats (n = 9) were anesthetized, and the left anterior descending coronary artery was ligated to provoke the MI. A sham-operated control group (CTRL) (n = 10) was treated without the MI. Two months later, a conductance catheter was inserted into the left ventricle (LV). The LV pressure and volume were measured and the E(n)(t(n)) derived. Slopes of E(n)(t(n)) during the preejection period (alpha(PEP)), ejection period (alpha(EP)), and their ratio (beta = alpha(EP)/alpha(PEP)) were calculated, together with the characteristic decay time during isovolumic relaxation (tau) and the normalized elastance at end diastole (E(min)(n)). MI provoked significant LV chamber dilatation, thus a loss in cardiac output (-33%), ejection fraction (-40%), and stroke volume (-30%) (P < 0.05). Also, it caused significant calcium increase (17-fold), fibrosis (2-fold), and LV hypertrophy. End-systolic elastance dropped from 0.66 +/- 0.31 mmHg/microl (CTRL) to 0.34 +/- 0.11 mmHg/microl (MI) (P < 0.05). Normalized elastance was significantly reduced in the MI group during the preejection, ejection, and diastolic periods (P < 0.05). The slope of E(n)(t(n)) during the alpha(PEP) and beta were significantly altered after MI (P < 0.05). Furthermore, tau and end-diastolic E(min)(n) were both significantly augmented in the MI group. We conclude that the E(n)(t(n)) differs quantitatively in all phases of the heart cycle, between normal and hearts post-MI. This should be considered when utilizing the single-beat concept.

The vitamin D(3) and nicotine (VDN) model is one of isolated systolic hypertension (ISH) in which arterial calcification raises arterial stiffness and vascular impedance. The effects of VDN treatment on arterial and cardiac hemodynamics have been investigated; however, a complete analysis of ventricular-arterial interaction is lacking. Wistar rats were treated with VDN (VDN group, n = 9), and a control group (n = 10) was included without the VDN. At week 8, invasive indexes of cardiac function were obtained using a conductance catheter. Simultaneously, aortic pressure and flow were measured to derive vascular impedance and characterize ventricular-vascular interaction. VDN caused significant increases in systolic (138 +/- 6 vs. 116 +/- 13 mmHg, P < 0.01) and pulse (42 +/- 10 vs. 26 +/- 4 mmHg, P < 0.01) pressures with respect to control. Total arterial compliance decreased (0.12 +/- 0.08 vs. 0.21 +/- 0.04 ml/mmHg in control, P < 0.05), and pulse wave velocity increased significantly (8.8 +/- 2.5 vs. 5.1 +/- 2.0 m/s in control, P < 0.05). The arterial elastance and end-systolic elastance rose significantly in the VDN group (P < 0.05). Wave reflection was augmented in the VDN group, as reflected by the increase in the wave reflection coefficient (0.63 +/- 0.06 vs. 0.52 +/- 0.05 in control, P < 0.05) and the amplitude of the reflected pressure wave (13.3 +/- 3.1 vs. 8.4 +/- 1.0 mmHg in control, P < 0.05). We studied ventricular-arterial coupling in a VDN-induced rat model of reduced arterial compliance. The VDN treatment led to development of ISH and provoked alterations in cardiac function, arterial impedance, arterial function, and ventricular-arterial interaction, which in many aspects are similar to effects of an aged and stiffened arterial tree.

Systemic amyloidosis with cardiac involvement may clinically be suspected in the presence of heart failure or arrhythmia of unknown origin. Herein two cases of cardiac amyloidosis are described with a clinical presentation of heart failure refractory to usual treatment. The key role of echocardiography in the diagnosis and prognosis evaluation of cardiac amyloidosis is discussed. A treatment targeted against the generation of amyloid fibril should ideally be initiated before apparition of heart failure.

The rodent model of myocardial infarction (MI) is extensively used in heart failure studies. However, long-term follow-up of echocardiographic left ventricular (LV) function parameters such as the myocardial performance index (MPI) and its ratio with the fractional shortening (LVFS/MPI) has not been validated in conjunction with invasive indexes, such as those derived from the conductance catheter (CC). Sprague-Dawley rats with left anterior descending coronary artery ligation (MI group, n = 9) were compared with a sham-operated control group (n = 10) without MI. Transthoracic echocardiography (TTE) was performed every 2 wk over an 8-wk period, after which classic TTE parameters, especially MPI and LVFS/MPI, were compared with invasive indexes obtained by using a CC. Serial TTE data showed significant alterations in the majority of the noninvasive functional and structural parameters (classic and novel) studied in the presence of MI. Both MPI and LVFS/MPI significantly (P < 0.05 for all reported values) correlated with body weight (r = -0.58 and 0.76 for MPI and LVFS/MPI, respectively), preload recruitable stroke work (r = -0.61 and 0.63), LV end-diastolic pressure (LVEDP) (r = 0.82 and -0.80), end-diastolic volume (r = 0.61 and -0.58), and end-systolic volume (r = 0.46 and -0.48). Forward stepwise linear regression analysis revealed that, of all variables tested, LVEDP was the only independent determinant of MPI (r = 0.84) and LVFS/MPI (r = 0.83). We conclude that MPI and LVFS/MPI correlate strongly and better than the classic noninvasive TTE parameters with established, invasively assessed indexes of contractility, preload, and volumetry. These findings support the use of these two new noninvasive indexes for long-term analysis of the post-MI LV remodeling.

Aim: Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima-media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population., Methods: The common carotid artery intima-media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high-definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age-matched healthy individuals (83 men, 37 women)., Results: The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706+/-211 microm and 749+/-395 microm, respectively) compared with that of the control population (614+/-113 microm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non-homogeneous intima-media thickening greater than 1.2 mm., Conclusion: This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.

Objective: Fabry disease is an X-linked disorder resulting from alpha-galactosidase A deficiency. The cardiovascular findings include left ventricular hypertrophy (LVH) and increased intima-media thickness of the common carotid artery (CCA IMT). The current study examined the possible correlation between these parameters. To corroborate these clinical findings in vitro, plasma from Fabry patients was tested for possible proliferative effect on rat vascular smooth muscle cells (vascular smooth muscle cell [VSMC]) and mouse neonatal cardiomyocytes., Methods and Results: Thirty male and 38 female patients were enrolled. LVH was found in 60% of men and 39% of women. Increased CCA IMT was equally present in males and females. There was a strong positive correlation between LV mass and CCA IMT (r2=0.27; P<0.0001). VSMC and neonatal cardiomyocyte proliferative response in vitro correlated with CCA IMT (r2=0.39; P<0.0004) and LV mass index (r2=0.19; P=0.028), respectively., Conclusions: LVH and CCA IMT occur concomitantly in Fabry suggesting common pathogenesis. The underlying cause may be a circulating growth-promoting factor whose presence has been confirmed in vitro.

Terminal heart failure can be the cause or the result of major dysfunctions of the organisms. Although, the outcome of the natural history is the same in both situations, it is of prime importance to differentiate the two, as only heart failure as the primary cause allows for successful mechanical circulatory support as bridge to transplantation or towards recovery. Various objective parameters allow for the establishment of the diagnosis of terminal heart failure despite optimal medical treatment. A cardiac index <2.0 l/min, and a mixed venous oxygen saturation <60%, in combination with progressive renal failure, should trigger a diagnostic work-up in order to identify cardiac defects that can be corrected or to list the patient for transplantation with/without mechanical circulatory support.

A family with several cases of severe cardiomyopathy and moderate myopathy is described, affecting two brothers and their cousin as well as their mothers. One boy died of sudden cardiac arrest at 17 years of age. The two brothers were treated with an implantable defibrillator and their mother died suddenly at 40 years of age. Muscle biopsy in males showed vacuolar myopathy in two cases, and no abnormality on standard staining in the third case. Cardiac biopsies showed hypertrophic and vacuolated fibres. Complete absence of LAMP-2 was demonstrated by immunohistochemistry on the vacuolated skeletal and cardiac muscle, but also on the morphologically normal skeletal muscle. Sequencing of LAMP-2 gene showed a novel S157X mutation in exon 4. Danon disease is a rare and potentially lethal cause of hypertrophic cardiomyopathy. Diagnosis can be made by immunohistochemistry performed on cardiac or muscle biopsy, and confirmed by genetic analysis, which also allows for easy family screening and counselling.

Aims: Mitral valve prolapse is a common source of severe mitral regurgitation in Western countries. Three-dimensional echocardiography can provide views of the entire valve, allowing a complete assessment of the valve leaflets and commissures. It has the potential to precisely locate and quantify mitral valve prolapse., Methods and Results: Between January 1997 and December 2000, 91 patients with severe mitral regurgitation due to mitral valve prolapse underwent a transesophageal echocardiography with three-dimensional reconstruction of the mitral valve as part of their pre-operative work-up. The location and extent of the prolapse by echo was compared to the surgical status. The volume of prolapsing leaflet was calculated and compared to the volume of resected tissue whenever a repair was attempted. There was an excellent correspondence between the echographic localization of the prolapse and surgical inspection, and between the volume of prolapsing and surgically resected tissue (r=0.94, p<0.0001)., Conclusions: In patients with severe mitral regurgitation due to mitral valve prolapse, 3D echo allowed a precise localization and an accurate quantification of the prolapsing portion of the leaflets. This technique can provide refinements in the surgical planning of mitral valve repair and in the selection of candidates for this intervention.

Background: An accurate diagnosis of patent foramen ovale (PFO) and atrial septal aneurysm (ASA) may be of decisional importance in the management of patients with ischemic stroke. Very few studies have been devoted to observer agreement in the diagnosis of these atrial septum abnormalities using contrast transesophageal echocardiography, which is considered as the method of choice for the diagnosis. The aim of this study was to assess interobserver and intraobserver variability in the diagnosis of PFO and ASA with contrast echocardiography., Methods: Three sonographers independently reviewed 100 contrast studies stored on videotape on 2 occasions each. The interobserver and intraobserver variability was assessed by calculating kappa statistics., Results: The overall interobserver and intraobserver kappa values for the assessment of degree of shunting through a PFO were 0.77 (first and second reading) and 0.82, respectively. The best kappa statistics were obtained when no and small shunts (less than 10 microbubbles) were pooled and compared with larger shunts. For the diagnosis of ASA, the overall interobserver kappa value was 0.45 for the first reading and 0.71 for the second reading, whereas the overall intraobserver kappa value was 0.74., Conclusion: Interobserver and intraobserver agreements for the diagnosis of PFO and ASA by transesophageal echocardiography are not perfect and need to be improved, particularly for ASA. This variability has to be taken into account when deciding on a potential risky treatment to prevent recurrent strokes.

In this study, which included 56 patients with aortic stenosis, the predictive value of the fractional shortening velocity ratio was evaluated. This Doppler index allowed detection of significant aortic stenosis (0.53 cm2/m2), with a positive predictive value of 93% and a negative predictive value of 92% for a cutoff value of 0.8.

Aims: Atrioventricular synchronous pacing exerts beneficial effects, including reduction of left ventricular outflow tract gradients, in patients with hypertrophic obstructive cardiomyopathy. The Pacing in Cardiomyopathy study was initiated to explore the effects of pacing in a double-blind randomized crossover fashion. The aims were to ascertain the beneficial effects of pacing in a controlled study and to rule out a placebo effect by pacing. This paper deals with the outcome of pacing on quality of life during 1 year of follow-up., Methods: Quality of life was evaluated with the Karolinska questionnaire, validated for patients paced for bradyarrhythmias and ischaemic heart disease. Drug-refractory patients with hypertrophic obstructive cardiomyopathy were recruited for the study and after a temporary pacing procedure implanted with permanent pacemakers. Patients were randomized to two study arms defining the sequence of pacemaker programming. In one arm the pacemaker was inactive, in the other active. After 3 months the pacemaker was reprogrammed to the alternate mode and a further 3 months followed. After this period subsequent pacemaker programming corresponded to the mode preferred by the patient. A last assessment was made 1 year after baseline examinations., Results: Eighty patients completed the first crossover period and 75 completed the full 1 year of follow-up. Active pacing induced significant quality of life improvements, in the order of 9-44%, regardless of programming sequence. Discontinuation of pacing after a first active period resulted in the return of symptoms. Fourteen patients requested early reprogramming after having been programmed to inactive pacing after a first period of active pacing. Seventy-six patients preferred active pacing after the crossover period. A further 6 months of pacing induced progressive improvement in symptoms already favourably influenced., Conclusion: Atrioventricular synchronous pacing has a profound beneficial effect on most domains of quality of life in patients with hypertrophic obstructive cardiomyopathy refractory to drug treatment., (Copyright 1999 The European Society of Cardiology.)

Background: The therapeutic options for hypertrophic obstructive cardiomyopathy (HOCM) classically include medical treatment with beta-blockers and calcium antagonists or myectomy-myotomy as a surgical possibility for refractory cases. The observation that pacemaker activation of the heart in HOCM reduces the subaortic gradient is well known but less well investigated., Methods: Eighty-three patients (33 female and 50 male) mean age 53 (18-82) years, with symptoms refractory to drug treatment and a resting gradient above 30 mmHg, who responded favourably to temporary pacing, were included in this prospective study and had a pacemaker (DDD) implanted. After an initial double-blind crossover phase of 6 months, patients were reinvestigated at 12 months and followed for a mean of 36 months., Results: As observed during a screening investigation, the obstruction was significantly reduced from 72 +/- 35 mmHg to 29 +/- 24 mmHg (P < 0.01) when the pacemaker was on, while no major effect was seen during the sham phase. The effect was persistent at 1 year with a remaining resting gradient of 28 +/- 24 mmHg. In parallel, we documented an improvement in functional capacity, according to the NYHA classification and by quality of life analysis, and a significant improvement in dyspnoea and angina. Exercise on treadmill improved only in patients with reduced initial tolerance (< 8 min). During the mean follow-up of 36 months, 65 patients remained on pacing alone, with eight patients having additional AV-node ablation and five patients finally having surgery., Conclusion: This controlled multicentre study shows that pacemaker treatment is an option for HOCM patients; it is inoffensive and does not exclude alternative methods, but satisfies 79% of patients beyond 3 years.

Assessment of right ventricular volume and function is important in many clinical settings involving heart or lung disease. However, the complexity of the right ventricular anatomy has prevented accurate volume determination by two-dimensional echocardiography. In the present study, 5 models incorporating standard echocardiographic views, were used to determine right ventricular volume in 10 human subjects. Two models were contingent on the true crescentic appearance of the right ventricle, whereas the remaining 3 calculated the right ventricular volume as a pyramid, an ellipsoid or other tapering geometrical figures, respectively. Subsequently, echocardiographic right ventricular volumes were compared to magnetic resonance imaging derived volumes. Correlation analysis and agreement measurement between the echocardiographic and magnetic resonance end-diastolic volume were performed in 10 out of 10 subjects and in 9 out of 10 subjects for the end-systolic volume. The 2 crescentic models resulted in the most reliable estimation of right ventricular volume. Those findings suggest that models based on right ventricular anatomical landmarks are feasible and should be preferred in echocardiographic studies.

Cardiac pacing using the apex of the right ventricle as site of excitation induces asynchronous contraction between the right ventricle and the left ventricle as well as inversion of the normal left ventricular activation sequence. These two phenomena are responsible for alteration of septal kinetics and overall contractility. It has recently been demonstrated that these alterations can be used to advantage to reduce the degree of subaortic obstruction of patients suffering from hypertrophic and obstructive cardiomyopathy, and to improve their exercise tolerance. Using an opposite approach, consisting of reducing the degree of asynchronous contraction related to the presence of intraventricular conduction disorders, while optimizing atrioventricular synchronism, new pacing methods have recently been able to improve cardiac output and functional tolerance of some patients suffering from dilated cardiomyopathy. Although cardiac pacing can now be considered to be an alternative a surgery for the treatment of refractory forms of hypertrophic and obstructive cardiomyopathy, it still constitutes a research technique in the field of dilated cardiomyopathy.

Background: Uncontrolled studies have shown that short atrioventricular delay dual chamber pacing reduces outflow tract obstruction in hypertrophic obstructive cardiomyopathy. Although the exact mechanism of this beneficial effect is unclear, this seems a promising potential new treatment for hypertrophic obstructive cardiomyopathy., Method: In order to evaluate the impact of pacing therapy, were performed a randomized multicentre double-blind cross-over (pacemaker activated vs non activated) study to investigate modification of echocardiography, exercise tolerance, angina, dyspnoea and quality of life in 83 patients with a mean age of 53 (range 22-87) years with symptoms refractory or intolerant to classical drug treatment., Results: After 12 weeks of activated or inactivated pacing, independent of which phase was first, the pressure gradient fell from 59 +/- 36 mmHg to 30 +/- 25 mmHg (P < 0.001) with active pacing. Exercise tolerance improved by 21% in those patients who at baseline tolerated less than 10 min of Bruce protocol; symptoms of dyspnoea and angina also improved significantly from NYHA class 2.4 to 1.4 and 1.0 to 0.4, respectively (P < 0.007). Quality of life assessment with a validated questionnaire objectivated the subjective improvement., Conclusion: Pacemaker therapy is of clinical and haemodynamic benefit for patients with hypertrophic obstructive cardiomyopathy, left ventricular outflow gradient at rest over 30 mmHg who are symptomatic despite drug treatment.

In order to assess the influence of right ventricular stimulation on LV contraction sequence in hypertrophic obstructive cardiomyopathy (HOCM), we performed a regional wall-motion analysis of the left ventricle by comparing normal His-Purkinje activation to pacing from the right ventricular apex. In 9 patients (5 males and 4 females, mean age 61 +/- 9 years) assessed after a mean pacing period of 12 weeks (range 7-24 weeks), AV sequential pacing induced a 52% reduction in maximal pressure gradient from 76 +/- 36 to 40 +/- 28 mmHg (P < 0.01) as determined by Doppler examination. Regional wall-motion analysis of the left ventricle was computed from digitized two-dimensional echocardiographic images by means of the area shrinking method. Pacing induced a significant reduction of total septal area shrinking from 25% +/- 17% to 12% +/- 17% (P < 0.005). A tendency toward paradoxical septal motion was observed in one patient only. The apex showed no significant variation. A 6% increase in area shrinking was observed at the posterior wall and lateral free wall, from 38% +/- 13% to 43% +/- 10% (P < 0.05). Pacing did not significantly alter the global ejection fraction. A direct correlation between the magnitude of subaortic pressure gradient reduction and that of septal motion changes was found in a majority of patients. In conclusion, dual chamber pacing reduces septal wall motion in patients with HOCM obstructive cardiomyopathy. This might be one of the mechanisms involved in the reduction of LV outflow tract obstruction.

Objective: To define therapeutic strategy for management of patients with ischemic stroke due to a high probability of paradoxical embolism through a Patent Foramen Ovale (PFO)., Methods: Since 1988 all consecutive patients with cerebrovascular events and PFO from the Stroke Registry of our population-based primary-care center are prospectively studied and followed. Since 1992, among 118 patients with cryptogenic embolic brain infarct or transient ischemic attack (TIA) and PFO, 32 consecutive patients younger than 60 years who presented at least two of the following criteria were admitted for surgery: history of Valsalva strain before stroke (11); multiple clinical events (13); multiple infarcts on brain Magnetic Resonance Imaging (MRI) (15); atrial septal aneurysm (ASA) (16); large right-to-left shunt (> 50 microbubbles) (12)., Results: Operative time 135' +/- 33'. CPB time 34' +/- 14'. Aortic crossclamping time 16' +/- 6'. Post-operative bleeding 485 +/- 170 ml. No homologous blood transfusion required. No neurological, cardiac or renal complications. All patients were followed-up corresponding to a cumulative time of 601 patient-months. This revealed no recurrent vascular events nor silent new brain lesions on brain MRI. Systematic simultaneous contrast Trans Esophageal Echocardiography (TEE)-Trans Cranial Doppler showed a small residual interatrial shunt in two patients., Conclusion: Surgical closure of a patent foramen ovale can be accomplished with very low morbidity and reduce efficiently the risk of stroke recurrence. It seems to be the option of choice in selected patients with a higher (> 1.5%/year) risk of stroke recurrence.

We hypothesized that pacing, which provided a rapid uniform contraction of the ventricles with a narrower QRS, would produce a better stroke volume and cardiac output (CO). We sought to study whether pacing simultaneously at two sites in the right ventricle (right ventricular apex and outflow tract) would provide a narrower QRS and improved CO in 11 patients undergoing elective electrophysiology studies. Patients were studied by transthoracic echocardiography measurement of CO using the Doppler flow velocity method in normal sinus rhythm, AOO pacing (rate 80), DOO pacing in the right ventricular apex (AV delay 100 ms), DOO pacing in the right ventricular outflow tract, and DOO pacing at both right ventricular sites simultaneously in random order. The COs were 5.42 +/- 1.83, 5.61 +/- 1.97, 5.67 +/- 1.6, 5.84 +/- 1.68, and 5.86 +/- 1.52 L/min, respectively (no significant difference by repeated measures analysis of variance [ANOVA]). The QRS durations were 0.09 +/- 0.02, 0.09 +/- 0.02, 0.13 +/- 0.027, 0.13 +/- 0.03, and 0.11 +/- 0.03 secs respectively. Repeated measures ANOVA showed that the QRS duration significantly increased with right ventricular apex or right ventricular outflow tract pacing compared to sinus rhythm and AOO pacing (P < 0.001) but then diminished with pacing at both sites (P < 0.01). QRS duration was not correlated with CO, however the change in QRS duration correlated significantly with the change in CO when pacing was performed at the two right ventricular sites simultaneously. In conclusion, during DOO pacing, there was a trend for pacing in the right ventricular outflow tract or both sites to improve the CO compared to the right ventricular apex. With simultaneous pacing at both ventricular sites, the QRS narrowed. Further studies will be required to see if this approach has value in patients with poor left ventricular function or congestive heart failure.

Our understanding of cardiac failure has greatly changed over the last 15 years. Left ventricular diastolic dysfunction, which is now recognised as one of the primary causes of certain types of cardiac failure (1). Abnormal left ventricular diastolic function is the common determinant and indeed the earliest sign of all chronic left ventricular failures whether systolic left ventricular dysfunction is associated with it or not (2). In this paper, we review the basis of diastolic dysfunction and its impact on diagnosis and treatment of cardiac failure.

Clinical improvement with dual chamber pacing has largely been reported in patients suffering from hypertrophic obstructive cardiomyopathy and mainly attributed to the reduction of the subaortic pressure gradient. To be effective, pacing must induce a permanent and complete capture of the LV. In two patients of our collective, symptoms (angina and dyspnea NYHA Class III and/or syncopes) persisted or relapsed despite pacing. This was related to the inability to obtain full LV capture due to a too-short native PR interval. RF ablation of the AV junction was therefore performed in both patients, resulting in permanent AV block in one and prolonged PR interval up 310 ms in the second. Pacing was thereafter associated with an immediate and significant clinical improvement related to permanent LV capture, whatever the patient's activity. After RF ablation, the AV delay was set up to induce the best LV filling, as assessed by Doppler analysis of mitral flow. Our observations suggest that RF ablation or modification of the AV junction can be a successful procedure in some patients with residual or recurrent symptoms, when the latter result from a loss of capture or from the inability to program an AV delay that does not compromise the active component to LV filling. Doppler echocardiography is a simple and effective mean to assess the hemodynamic effect of AV interval modulation in this setting.

All studies concerning the detection of patent foramen ovale (PFO) have compared transthoracic or transesophageal echocardiography (c-TEE) to transcranial Doppler ultrasound after contrast injection (c-TCD), but combining both techniques in the search of PFO has received no consideration. Our study aims to substantiate this claim in 37 patients with cryptogenic stroke. It includes two protocols for the detection of PFO to assess the complementarity of c-TCD and c-TEE performed simultaneously or separately. Firstly, we used a standardized protocol, performing c-TCD alone. Secondly, we used a standardized and a simultaneous protocol which associated c-TCD with c-TEE. When c-TCD and/or c-TEE found right-to-left shunts, they were classified as minimal, intermediate and massive. c-TCD revealed all PFO detected by c-TEE in 24 patients out of 37 (65%). Furthermore, c-TCD was positive for a PFO in 5 other patients whereas c-TEE was negative. The degree of right-to-left interatrial shunting varied according to the protocol: c-TCD performed alone found 15 massive, 4 intermediate and 5 minimal shunts whereas 10, 9 and 5, respectively, were detected by c-TCD when it was combined with c-TEE. In contrast, c-TEE revealed 8 massive, 8 intermediate and 8 minimal shunts. c-TCD can identify minimal shunts missed by c-TEE and could be more relevant to detect massive shunts, particularly when not performed simultaneously with c-TEE because no sedation is required for c-TCD alone as opposed to c-TEE: thus patients are more cooperative and produce a better Valsalva strain. c-TEE confirms pulmonary shunts suspected by c-TCD and determines the morphologic characteristics of the interatrial septum. While previous studies opposed c-TEE against c-TCD for the detection of a PFO, we think that both techniques are complementary and that it is interesting to associate them, particularly when they are deferred, to increase the ability of detecting PFO and to specify the degree of right-to-left shunting.

Background: The risk of stroke and the long-term prognosis of recurrent strokes in young patients with patent foramen ovale (PFO) are not well known. For this reason, the treatment of these patients remains empirical. An alternative treatment to prolonged antithrombotic therapy may be surgical closure of the PFO., Methods: Thirty patients (20 men and 10 women) with stroke and PFO were prospectively selected among 138 patients with stroke and PFO for a study of surgical closure of PFO at our center. Eligible patients were < 60 years old, had negative results of a systematic search for another cause of stroke (first criterion), and met two of the four following criteria: (1) recurrent clinical cerebrovascular events or multiple ischemic lesions on brain MR, (2) PFO associated with an atrial septal aneurysm, (3) > 50 microbubbles counted in the left atrium on contrast transesophageal echocardiography (TEE), and (4) Valsalva maneuver or cough preceding the stroke. Patients selected in this manner for surgery were considered to be a subgroup with a higher risk of stroke recurrence., Results: All patients had a direct suture of PFO while under cardiopulmonary bypass without recorded early or delayed significant complication. All patients underwent a new brain MRI and TEE simultaneous with transcranial Doppler ultrasonography after contrast injection at 8 +/- 3 months after surgery. After a mean follow-up of 2 years without antithrombotic treatment, no recurrent cerebrovascular event (stroke or transient ischemic attack [TIA]) and no new lesion on MRI had developed. Postoperative contrast TEE and transcranial Doppler ultrasonography showed that two patients had residual interatrial right-to-left shunting, although much smaller than before surgery, associated with single versus double continuous suture., Conclusions: Our study of 30 selected stroke patients with surgical suture of PFO showed a stroke recurrence rate of 0% and no significant complication. Residual right-to-left shunting may be avoided by double continuous suture of the PFO. In the absence of controlled studies to guide individual therapeutic decisions, our findings show that PFO closure can be done safely and may be considered to avoid recurrence in selected patients with long life expectancy and presumed paradoxic embolism.

Advancing The Standard (ATS) Medical (ATS Medical Inc., Minneapolis, MN) is a new mechanical bileaflet valve, composed of pyrolitic carbon. The aim of this study was to define in a blinded manner the Doppler echocardiographic characteristics of normally functioning ATS Medical prostheses with respect to their size. Forty consecutive patients (29 men, mean age 58 +/- 13 years), clinically stable, and without evidence of valve dysfunction, were studied from 1993 to 1995. Doppler echocardiography was performed at least 3 months after valve replacement with ATS Medical valves (5 n degrees 21, 8 n degrees 23, 12 n degrees 25, 10 n degrees 27, 5 n degrees 29). Maximum and mean transprosthetic pressure gradients were calculated by the simplified Bernoulli equation. Functional valve surface area was assessed by the continuity equation using the external diameter of the prostheses to calculate the subaortic surface area. The Doppler velocity index was obtained by the ratio of subaortic and transaortic velocities and the performance index was calculated dividing the effective orifice area by the actual orifice area. For the most commonly used aortic valve (25 mm), the maximum pressure gradient was 17 +/- 8 mmHg, the mean gradient 11 +/- 4 mmHg, the functional surface area 2.2 +/- 0.4 cm2, the Doppler velocity index 0.44 +/- 0.07, and the performance index 0.68 +/- 0.11. This study provides the normal range for Doppler hemodynamic characteristics of the various sizes of the ATS valve.

Prevention of recurrent stroke in adults with patent foramen ovale represents a therapeutic challenge. Antiplatelet or anticoagulant treatment is widely introduced, but its exact indication is not known. In this pilot study, eight men and three women with previous ischemic cerebral events underwent direct surgical closure of the patent foramen ovale. Mean age was 39.4 (from 30 to 58) years. No coexisting cause of stroke was found after extensive investigations, including blood and coagulation tests, echocardiography, 24-hour three-lead electrocardiographic monitoring, extracranial and transcranial Doppler ultrasonography, and cerebral angiography. Criteria for operation also included at least two of the following: atrial septal aneurysm, multiple cerebral infarcts, a history of multiple cerebral events, and Valsalva strain before stroke. Before operation, one patient had two shunts (1 patent foramen ovale, 1 intrapulmonary shunt). No intraoperative or postoperative complications occurred, but a few hours after operation transient arrhythmias developed in two patients without atrial fibrillation, hemodynamic instability, or embolism. During a median follow-up of 12.2 months, no patient had recurrent stroke. All patients prospectively underwent brain magnetic resonance imaging and contrast echocardiography with simultaneous transcranial Doppler ultrasonography. A residual right-to-left interatrial shunt, smaller than the preoperative one, was observed in only one patient, whereas no lesion was seen on magnetic resonance imaging. Our study suggests that surgical closure of patent foramen ovale in patients with presumed paradoxic embolism is safe, with no recurrent stroke in the first year of follow-up. Further studies are needed to evaluate the long-term prognosis of patients with versus without operation and to define the role of operation as an alternative to prolonged antithrombotic treatment.

Patent foramen ovale (PFO) is more common in patients with stroke than in matched controls, but the stroke mechanism and late prognosis are not well known. We studied features, coexisting causes, and recurrences of stroke in 140 consecutive patients (mean age 44 +/- 14 years) with stroke and PFO admitted to a population-based primary-care center. We selected the patients from 340 patients (41%) aged < or = 60 years with acute stroke. The initial event was brain infarction in 118 patients (84%) and TIA in 22 (16%). Intracranial embolic occlusions were present on angiography or transcranial Doppler in most patients admitted within 12 hours of onset, whereas a venous source was clinically apparent in only six patients (5.5%). Pulmonary embolism, Valsalva maneuver at onset, and coagulation abnormalities were rare, but one-fourth of the patients had an interatrial septum aneurysm (ISA) that coexisted with PFO. An alternative cause of stroke was present in only 22 patients (16%), usually cardiac (atrial fibrillation, severe mitral valve prolapse, akinetic left ventricular segment). During a mean follow-up of 3 years, the stroke or death rate was 2.4% per year, but only eight patients had a recurrent infarct (1.9% per year). This low rate of recurrence contrasted with the severity of initial stroke, which left disabling sequelae in one-half the patients. Multivariate analysis showed that interatrial communication, a history of recent migraine, posterior cerebral artery territory infarct, and a coexisting cause of stroke were associated with recurrence, whereas ISA and treatment type (coagulant or antiaggregant therapy, surgical closure of PFO) were not. However, given the low number of events, these findings must be taken with caution. In conclusion, our study shows that stroke associated with PFO with or without ISA is not commonly due to a coexisting cause of stroke. It is usually embolic, although a definite source cannot often be demonstrated. The presenting stroke is often severe, but recurrence is uncommon. The demonstration of factors associated with a higher risk of recurrence in subgroups of patients is critical for the long-term management of these patients.

Pacing reduces the sub-aortic pressure gradient in hypertrophic obstructive cardiomyopathy. This phenomenon was described long ago but only recently, with the development of sophisticated pacemakers, has it become possible to use pacemakers for the long term treatment of this disease. The acute hemodynamic improvement with pacemaker treatment is well documented. The reason for this acute and chronic improvement is of multiple origin. Pacing modulates the activation sequence of the left ventricle, reduces contractility, reduces subaortic flow velocities, influences mitral valve movement and leads to remodeling of the ventricle in the long term. All these factors together explain the clinical and hemodynamic improvement in patients suffering from hypertrophic obstructive cardiomyopathy.