PREVENTION-ACHD: PRospEctiVE study on implaNTable cardioverter-defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease; Rationale and Design.

BACKGROUND: Many adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). An implantable cardioverter-defibrillator (ICD) may prevent SCD, but the evidence for primary prevention indications is still unsatisfactory. STUDY DESIGN: PREVENTION-ACHD is a prospective study with which we aim to prospectively validate a new risk score model for primary prevention of SCD in ACHD patients, as well as the currently existing guideline recommendations. Patients are screened using a novel risk score to predict SCD as well as current ICD indications according to an international Consensus Statement. Patients are followed up for two years. The primary endpoint is the occurrence of SCD and sustained ventricular arrhythmias. The Study was registered at ClinicalTrials.gov (NCT03957824). CONCLUSION: PREVENTION-ACHD is the first prospective study on SCD in ACHD patients. In the light of a growing and aging population of patients with more severe congenital heart defects, more robust clinical evidence on primary prevention of SCD is urgently needed.

Cerebrovascular accidents in adult patients with congenital heart disease.

OBJECTIVE: To investigate the prevalence and characteristics of cerebrovascular accidents (CVA) in a large population of adults with congenital heart disease (CHD). METHODS AND RESULTS: In a retrospective analysis of aggregated European and Canadian databases a total population of 23 153 patients with CHD was followed up to the age of 16-91 years (mean 36.4 years). Among them, 458 patients (2.0%) had one or more CVA, with an estimated event rate of 0.05% per patient-year. Permanent neurological sequelae were noted in 116 patients (25.3%). The prevalence of CVA in selected diagnostic categories was as follows: open atrial septal defect 93/2351 (4.0%); closed atrial or ventricular septal defect 57/4035 (1.4%); corrected tetralogy of Fallot 52/2196 (2.4%); Eisenmenger physiology 24/467 (5.1%); other cyanotic 50/215 (23.3%); mechanical prostheses (29/882 (3.3%). Associated conditions in patients with CVA were absence of sinus rhythm (25%), transvenous pacemakers (7%), endocarditis (2%), cardiac surgery (11%) and catheter intervention (2%), but with the exception of absent sinus rhythm these were not significantly more prevalent in patients with CVA. CONCLUSION: CVA are a major contributor to morbidity in this young population despite absence of classical cardiovascular risk factors. Although the prevalence of CVA in patients with CHD appears low, it is 10-100 times higher than expected in control populations of comparable age. Residua occur in a strong minority of patients. The subjects at highest risk are those patients with CHD with cyanotic lesions, in whom the prevalence is over 10-fold above the average.

Premature death in adults with 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disease with a prevalence of 1/4000. Variable expression of congenital and later onset features contributes to its under-recognition. Longevity in those surviving childhood is believed to be normal but data are limited. METHODS: We prospectively followed 264 subjects; 102 adults (>17 years) with 22q11.2DS (44 male (M), 58 female (F); mean (SD) age 33.6 (10.9) years) and their 162 unaffected siblings (77 M, 85 F; mean age 36.1 (12.2) years). We compared survival between groups using Kaplan-Meier estimates. RESULTS: Twelve (11.8%; 4 M, 8 F) individuals with 22q11.2DS and no siblings died (p<0.0001). Survival to ages 40 and 50 years was 89.9% and 73.9%, respectively. Median age at death was 41.5 (range 18.1-68.6) years. Deaths included two (7.7%) of 26 subjects with neither major congenital heart disease (CHD) nor schizophrenia. Four of six sudden and unexpected deaths occurred in individuals with no major CHD. There was no evidence of cancer or coronary artery disease or family history of sudden death in the 12 patients who died, six of whom had autopsies. DISCUSSION: Individuals with 22q11.2DS who survive childhood have diminished life expectancy and increased risk of sudden death not attributable to any single factor. Some sudden and/or premature deaths observed in the general population may represent undiagnosed 22q11.2DS. Increased recognition of the syndrome by family doctors, specialists and coroners will be essential to facilitate the tissue studies needed to determine underlying mechanisms.

Isolated left ventricular noncompaction as a cause for heart failure and heart transplantation: a single center experience.

OBJECTIVES: To determine the prevalence of isolated left ventricular noncompaction (IVNC) as a cause of heart failure and heart transplantation. METHODS: There were 960 patients seen in the heart failure clinic from 1987 to 2005, with a complete evaluation including echocardiography at our center (study population, 82% men, mean age 52 years). The following data were collected: type of heart disease, age at echocardiography and at heart transplantation, and frequency of heart transplantation. Echocardiographic diagnosis of IVNC was based on our published criteria. RESULTS: The etiologies of heart failure were coronary artery disease (CAD; 37%), idiopathic dilated cardiomyopathy (33%), valvular heart disease (11%), congenital heart disease (5%), IVNC (3%), hypertensive heart disease (3%), hypertrophic cardiomyopathy (2%), myocarditis (1%), and <1% other diagnoses. Heart transplantation was performed in 253 patients (26%) due to idiopathic dilated cardiomyopathy (42%), CAD (39%), valvular heart disease (5%), congenital heart disease (5%), IVNC (2%), or other etiologies (< or =1% each). CONCLUSIONS: The most common causes for heart failure remain idiopathic dilated cardiomyopathy, CAD and valvular heart disease. Strictly using the criteria for the definition of IVNC, IVNC is a rare underlying cardiomyopathy for both, heart failure (2.7%) and heart transplantation (2%) in our center.

Is transesophageal echocardiography still necessary to exclude patent foramen ovale?

OBJECTIVES: Current guidelines still recommend transesophageal echocardiography (TEE) as reference method to diagnose interatrial shunts. The aim was to test the accuracy of high-end transthoracal echocardiography (TTE) to exclude inter-atrial shunts. METHODS: Prospective TTE and TEE study with second harmonic imaging to determine left-to-right shunt (L/R) by both colour Doppler or R/L by contrast echocardiography in patients with unexplained cerebrovascular incidents or newly detected valvular or myocardial disease. RESULTS: An inter-atrial shunt was diagnosed in 200 of 438 analyzed patients (117 males). Colour Doppler echocardiography visualized a shunt in 67 patients (34%) on TTE vs. 84 (42%) patients on TEE (p <0.0001). However injection of agitated blood with a valsalva maneuver detected 190 (95%) interatrial shunts by both TTE and TEE, but 10 shunts (5%) only by TTE. CONCLUSIONS: Our study shows that patent foramen ovale can safely be demonstrated with high-end transthoracic contrast- echocardiography. If additional studies confirm our results, TTE has the potential to become the method of choice in the diagnosis of PFO.

Isolated ventricular non-compaction of the myocardium in adults.

Isolated ventricular non-compaction (IVNC) in adults is a genetic cardiac disease of emerging importance with a distinct clinical and pathophysiological presentation. The body of evidence for the underlying genetic basis of the disease has also grown. Prognosis remains poor for patients with impaired systolic left ventricular function, as treatment options are very limited. The diagnosis of IVNC, however, is often missed, most often as a consequence of ignorance of the condition. The relevant clinical issues and the emerging concepts of the aetiology of IVNC are summarised.

WITHDRAWN: Enlargement of the Right Atrium - Diverticulum or Aneurysm?

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 223-225, . The duplicate article has therefore been withdrawn.

Simple criteria for differentiation of Fabry disease from amyloid heart disease and other causes of left ventricular hypertrophy.

AIMS: Fabry disease may be difficult to differentiate from other causes of left ventricular hypertrophy such as other myocardial storage diseases (including amyloidosis), hypertrophic cardiomyopathy (HCM), or hypertensive heart disease (HHD). We sought to determine simple criteria to best differentiate the above mentioned cardiac diseases. METHODS AND RESULTS: All patients in a six-year time period with left ventricular hypertrophy due to Fabry disease (13 patients), biopsy proven cardiac amyloidosis (16 patients), non-obstructive HCM (17 patients), and 22 randomly selected patients with advanced HHD were compared. Retrospective analysis of clinical characteristics, findings of electrocardiogram (ECG) and echocardiography by blind review was performed. RESULTS: No single clinical characteristic or findings of ECG or echocardiography could reliably differentiate between the various diseases. Increased echogenicity/granular sparkling, valvular abnormalities, abnormal renal function, and diastolic function were not helpful discriminators. In a univariate analysis, four criteria (acroparesthesia, anhydrosis, absence of hypertension and presence of Sokolow criteria for left ventricular hypertrophy in the ECG) were significant for Fabry disease. By logistic regression analysis, the following most suitable discriminative parameters were identified: hypertension in HHD (specificity 82%), orthostasis and/or pericardial effusion for amyloidosis (specificity 93%), papillary muscle anomaly in non-obstructive HCM (specificity 92%), and Fabry disease if neither hypertension orthostatis, pericardial effusion nor a papillary muscle anomaly was present (specificity 87%). CONCLUSION: A combination of symptoms, echocardiographic findings and ECG in unexplained left ventricular hypertrophy may help to differentiate amyloidosis, non-obstructive HCM and hypertensive heart disease from Fabry disease. The results of this preliminary study will have to be confirmed in a prospective study.

Predictors of adverse outcome in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy: long term experience of a tertiary care centre.

OBJECTIVE: To investigate the predictors for adverse clinical outcome in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) during long term follow up. METHODS: 61 patients with ARVD/C were studied to assess the impact of family history, clinical findings, surface ECG parameters, echocardiographic findings, and electrophysiological findings on clinical outcome. The prevalence of these risk factors were compared in two patient groups: group A (patients with adverse clinical outcome: sudden cardiac death, death from heart failure, or heart transplant) and group B (survivors excluding patients who received a heart transplant). RESULTS: Mean age at first diagnosis was 44 (14) years. The mean follow up duration was 55 (47) months. Ten patients (16%) died during follow up. The cause of death of eight of these patients was probably arrhythmic. Two patients died of advanced heart failure. Five patients underwent heart transplantation because of terminal heart failure. Risk factors significantly associated with adverse outcome were history of congestive heart failure (p < 0.001), the presence of left ventricular involvement on echocardiography (p < 0.001), left atrial dilatation (p < 0.05), prolonged PR duration (p < 0.01), prolonged QRS in V1 (p < 0.05), and bundle branch block (p < 0.05). In multivariate analysis, history of congestive heart failure and presence of left ventricular involvement were identified as independent risk predictors for an adverse outcome. CONCLUSIONS: Congestive heart failure and left ventricular involvement are independently associated with adverse outcome in patients with ARVD/C during long term follow up.

Transregional spread of a single clone of methicillin-resistant Staphylococcus aureus between groups of drug users in Switzerland.

BACKGROUND: An epidemic spread of methicillin-resistant Staphylococcus aureus (MRSA) among intravenous drug users (IDUs) has been observed in Zurich. In the present study we investigated the situation in the Grisons, Switzerland. PATIENTS AND METHODS: We screened IDUs and their caregivers in medical and socio-therapeutical institutions in the Grisons for MRSA. Nose swabs were used for bacterial culture and pulsed-field gel electrophoresis for MRSA genotyping. RESULTS: A total of 191 nose swabs from 111 IDUs and 80 caregivers was analyzed. None of the caregivers was MRSA positive. Six IDUs were asymptomatic MRSA carriers (5.4%). They participated in the official heroin program (MRSA prevalence in this group 16%). The MRSA genotype was identical with the single clone found in IDUs in Zurich, strongly suggesting an epidemic spread. Decolonization was successful in two persons only. Persistence of MRSA in IDUs must therefore be assumed. CONCLUSION: We conclude that a single clone of MRSA, found in IDUs in Zurich, has spread to a distant region of Switzerland. A rigorous infection control program in all institutions with IDUs is necessary to prevent a further spread of MRSA.

[Cardiac indications for oral anticoagulation]. / Kardiologische Indikationen zur oralen Antikoagulation.

While considering long-term oral anticoagulation one should assess benefit (i.e., reduction in thromboembolic events) and risks (i.e., bleeding complications) associated with therapy for each individual patient. The classic cardiac indications for oral anticoagulation include chronic atrial fibrillation, prosthetic heart valves, and left ventricular thrombus formation following anterior myocardial infarction. The value of anticoagulation in patients with impaired left ventricular function in stable sinus rhythm and in secondary prevention of coronary artery disease remains controversial. For decades warfarin has been the only compound available. Currently, promising results have been achieved with the oral thrombin inhibitor ximelagatran. In the future, oral anticoagulants, which are administered in fixed dose with no need for monitoring of the anticoagulation level, may replace warfarin. Safety and efficacy of double antiplatelet therapy (aspirin and clopidogrel) in the secondary prevention of thromboembolic events in patients with atrial fibrillation are currently being addressed in large-scale clinical trials.

Idiopathic enlargement of the right atrium: 23 year follow up of a familial cluster and their unaffected relatives.

OBJECTIVE: To evaluate the long term outcome of familial idiopathic enlargement of the right atrium (IERA) and the risk of developing this disorder among unaffected offspring. DESIGN: 23 year follow up study. PATIENTS: 14 members (eight men, mean age 54 years, range 40-78) of a pedigree with familial IERA. METHODS: All patients were examined clinically and echocardiographically in 1979 and 2002. Normal cross sectional dimensions of the right atrium were derived from echocardiographic evaluation of 100 people (47% men) with no structural or haemodynamic signs of heart disease. The 90th centile was chosen as the upper normal limit. IERA was defined as an increased right atrial long axis indexed to body surface area (RALAX(i), men > 2.6 cm/m2, women > 2.8 cm/m2) in the absence of other cardiac abnormalities. Severe IERA was defined arbitrarily as RALAX(i) > or = 4 cm/m2. RESULTS: The course of the two index patients with severe IERA diagnosed in 1979 was complicated by atrial fibrillation, systemic embolism, and symptoms of heart failure without systolic dysfunction, resulting in the death of one man (77 years old). One of two patients with initially mild forms progressed to severe IERA. All of the initially unaffected offspring (n = 9) remained asymptomatic, although four of them had developed mild IERA. CONCLUSIONS: During 23 years' follow up, severe IERA induced atrial fibrillation, systemic embolism, and symptoms of heart failure without systolic dysfunction in all cases in this family. Mild IERA seems to become manifest during middle age and may be followed by gradual progression to clinically relevant disease.

Aberrant tendinous chords with tethering of the tricuspid leaflets: a congenital anomaly causing severe tricuspid regurgitation.

OBJECTIVE: To define the entity of tricuspid regurgitation caused by tethering of the tricuspid valve leaflets by aberrant tendinous chords. DESIGN: Retrospective study. SETTING: Tertiary care centre (university teaching hospital). PATIENTS: 10 patients with unexplained severe tricuspid regurgitation. METHODS: The last 13 500 echocardiographic studies from our facility were reviewed to identify patients with severe unexplained tricuspid regurgitation. Tethering was defined by the presence of aberrant tendinous chords to the tricuspid valve leaflets limiting the mobility of the tricuspid leaflet and resulting in incomplete coaptation and apical displacement of the regurgitant jet origin. Aberrant tendinous chords were defined as those inserting at the clear zone of the tricuspid leaflet and not originating from the papillary muscle. Patients fulfilling the diagnostic criteria for Ebstein's anomaly were excluded. RESULTS: 10 patients with aberrant tendinous chords tethering one or more tricuspid valve leaflets were identified. There were short non-aberrant tendinous chords in seven patients, five of whom also had right ventricular or tricuspid annulus dilatation. CONCLUSIONS: Tethering of the tricuspid valve leaflets by aberrant tendinous chords can be the sole mechanism of congenital tricuspid regurgitation. It is often associated with short non-aberrant tendinous chords, which may develop secondary to right ventricular or tricuspid annulus dilatation. Awareness of tethering as a cause of tricuspid regurgitation may be important in planning reconstructive surgery.

Intractable ventricular tachycardia and bridging to heart transplantation with a non-pulsatile flow assist device in a patient with isolated left-ventricular non-compaction.

Intractable ventricular tachycardia was investigated in a 51-year-old man with isolated left ventricular non-compaction during implantation of an automated internal cardioverter-defibrillator. Favorable bridging to cardiac transplantation was achieved with the DeBakey left ventricular assist device (LVAD).

Enlargement of the right atrium--diverticulum or aneurysm?

Diverticula and aneurysms are rare congenital anomalies of the right atrium. Here, we report a case of a giant congenital diverticulum of the right atrium in a 27-year-old female and discuss the morphological characteristics distinguishing diverticula and aneurysms.

Left ventricular assist device as bridge to heart transplantation--lessons learned with the MicroMed DeBakey axial blood flow pump.

OBJECTIVE: The MicroMed DeBakey left ventricular assist device (LVAD) axial blood flow pump was used as bridge to heart transplantation (HTx) in patients with terminal heart failure. The aim was to evaluate this novel mechanical circulatory support system in regard to overall outcome. METHODS: Prospective study in 15 HTx candidates (mean age 40+/-7 years) with terminal heart failure and maximal medical treatment due to ischemic cardiomyopathy (CMP, n=5), dilated CMP (n=3), restrictive CMP (n=2), unclassified CMP (n=1), metabolic CMP (n=1), valvular CMP (n=1) and congenital CMP (n=2). All patients were implanted with a MicroMed DeBakey LVAD. A rescue procedure was necessary in eight critical patients, while seven underwent elective LVAD implantation. Procedures were performed via median sternotomy, in normotherm femoro-femoral CPB (mean duration 59+/-1 min). Oral Marcoumar (INR 2.0-3.0) and Aspirin (100 mg daily) were started as soon as possible. Patients were discharged into a specialized rehabilitation clinic from which it was possible to release them home after a few weeks. RESULTS: Successful implantation and discharge from ICU (mean stay 10+/-7 days) was possible in 11 patients. Seven were transplanted (mean support 50.7 days) and one is awaiting HTx (support >310 days) in the comfort of his home (NYHA I). Survival was 100% among the transplanted patients. Of the seven elective implants, five, and of the eight rescue procedures three patients underwent successful HTx. Four patients died early, while three patients died late on pump support due to intracranial hemorrhage (n=2, 73 and 76 days) and chest infection (n=1, 124 days). All survivors were discharged from hospital, with significant decrease in NYHA class (mean 3.8-2.4 (n=11)). Treadmill testing showed increased exercise tolerance, from 35 to 71W (n=4). Plasma BNP values (mean 950-162 ng/l (n=4)) and pulmonary resistance (mean 316-194.5 dyne s/cm(5) (n=3)) decreased significantly during LVAD support. CONCLUSIONS: The MicroMed DeBakey LVAD is simple to implant; outpatient treatment is safe and efficient. Patients' condition and pulmonary resistances normalize within 6 weeks, making previously considered inoperable patients amenable for HTx. HTx can be performed in low-risk situation, allowing better donor-recipient matching and improving overall outcome.