Hubert Seggewiss

Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases

In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.

Nonsurgical Septal Reduction for Hypertrophic Obstructive Cardiomyopathy Outcome in the First Series of Patients

BACKGROUND Some patients with hypertrophic obstructive cardiomyopathy may gain symptomatic relief from a reduction in the extent of obstruction to left ventricular outflow. We present the outcome of the first series of patients treated with an alternative method of gradient reduction using catheter techniques. METHODS AND RESULTS Eighteen patients were treated with selective intracoronary alcohol injection to induce localized septal infarction. Patients underwent echocardiographic measurement of left ventricular dimensions and Doppler echocardiographic evaluation of left ventricular outflow tract gradients before the procedure, on the first postoperative day, and at a median follow-up of 3 months after the procedure. In addition, patients underwent exercise testing and symptom evaluation before and 3 months after nonsurgical septal reduction. There was a significant reduction in left ventricular outflow tract obstruction after the procedure (preprocedure, 67 mm Hg [95% CI, 48 to 87 mm Hg]; postprocedure, 25 mm Hg [95% CI, 16 to 34 mm Hg]; P=.0006), which persisted at 3-month follow-up (22 mm Hg [95% CI, 12 to 32 mm Hg]; P=.001). This was associated with a significant improvement in symptoms. There was a small but not significant increase in exercise capacity (n=10; preprocedure, 418 seconds [95% CI, 273 to 563 seconds]; postprocedure, 452 seconds [95% CI, 283 to 621 seconds). Left ventricular dimensions were not significantly altered by nonsurgical septal reduction. CONCLUSIONS Nonsurgical septal reduction significantly reduces left ventricular outflow tract obstruction and improves symptoms in some patients with hypertrophic obstructive cardiomyopathy. The technique may provide an alternative to surgical myomectomy in selected patients.

Percutaneous Transluminal Septal Myocardial Ablation in Hypertrophic Obstructive Cardiomyopathy Results With Respect to Intraprocedural Myocardial Contrast Echocardiography

BACKGROUND Percutaneous transluminal septal myocardial ablation (PTSMA) has been introduced as an alternative procedure for reducing the left ventricular outflow tract gradient (LVOTG) in hypertrophic obstructive cardiomyopathy. We report on the acute and mid-term results in 91 symptomatic patients with respect to intraprocedural myocardial contrast echocardiography (MCE). METHODS AND RESULTS PTSMA was intended for 46 women and 45 men (54.1+/-15.5 years). In 2 patients, the intervention could not be completed. In the first 30 patients the target vessel was determined by probatory balloon occlusion alone and in the remainder by additional intraprocedural MCE. Resting LVOTG was reduced from 73.8+/-35.4 to 16.6+/-18.1 and nostextrasystolic LVOTG from 149.3+/-42.5 to 61. 9+/-43.0 mm Hg (P<0.0001 each). In 10 (11%) patients, permanent DDD pacemaker implantation was necessary. Two (2%) patients died, 1 from ventricular fibrillation associated with treatment for chronic obstructive pulmonary disease after 9 days and 1 from fulminant pulmonary embolism after 2 days. After 3 months, mean New York Heart Association class was reduced from 2.8+/-0.6 to 1.1+/-1.0 (P<0.0001). The LVOTG remained reduced to 14.6+/-25.5 mm Hg at rest and 49. 1+/-48.7 mm Hg (P<0.0001 each). Four patients underwent successful repeat PTSMA. Determination of the target vessel by MCE was associated with a higher rate of acute (92% vs 70%; P<0.01) and mid-term (94% vs 64%; P<0.01) success. CONCLUSIONS PTSMA is a promising nonsurgical technique for reduction of symptoms and LVOTG in hypertrophic obstructive cardiomyopathy. MCE has been shown to be a useful addition to probatory balloon occlusion for target vessel selection. Prospective, long-term observations of larger populations and a comparison with the established forms of therapy are necessary to determine the definitive significance of PTSMA.

Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: acute results and 3-month follow-up in 25 patients.

OBJECTIVES We report the acute results and midterm clinical course after percutaneous transluminal septal myocardial ablation (PTSMA) in symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND In the treatment of HOCM, surgical myectomy and DDD pacemaker therapy are considered the standard procedural extensions to drug therapy with negatively inotropic drugs. As an alternative nonsurgical procedure for reducing the left ventricular outflow tract (LVOT) gradient, PTSMA by alcohol-induced septal branch occlusion was introduced. However, clinical follow-up has not been sufficiently described. METHODS In 25 patients (13 women, 12 men; mean [+/- SD] age 54.7 +/- 15.0 years) who were symptomatic despite sufficient drug therapy, 1.4 +/- 0.6 septal branches were occluded with an injection of 4.1 +/- 2.6 ml of alcohol (96%) to ablate the hypertrophied interventricular septum. After 3-months, follow-up results of LVOT gradients and clinical course were determined. RESULTS The invasively determined LVOT gradients could be reduced in 22 patients (88%), with a mean reduction from 61.8 +/- 29.8 mm Hg (range 4 to 152) to 19.4 +/- 20.8 mm Hg (range 0 to 74) at rest (p < 0.0001) and from 141.4 +/- 45.3 mm Hg (range 76 to 240) to 61.1 +/- 40.1 mm Hg (range 0 to 135) after extrasystole. All patients had angina pectoris for 24 h. The maximal creatine kinase increase was 780 +/- 436 U/liter (range 305 to 1,810) after 11.1 +/- 6.0 h (range 4 to 24). Thirteen patients (52%) developed a trifascicular block for 5 min to 8 days requiring temporary (n = 8 [32%]) or permanent (DDD) pacemaker implantation (n = 5 [20%]). An 86-year old woman died 8 days after successful intervention of uncontrollable ventricular fibrillation in conjunction with beta-sympathomimetics in chronically obstructive pulmonary disease. The remaining patients were discharged after 11.3 +/- 5.4 days (range 5 to 24), after an uncomplicated hospital course. Clinical and echocardiographic follow-up was achieved in all 24 surviving patients after 3 months. No cardiac complications occurred. Twenty-one patients (88%) showed clinical improvement, with a New York Heart Association functional class of 1.4 +/- 1.1. A further reduction in LVOT gradient was shown in 14 patients (58%). CONCLUSIONS PTSMA of HOCM is a promising nonsurgical technique for septal myocardial reduction, with a consecutive reduction in LVOT gradient. Possible complications are trifascicular blocks, requiring permanent pacemaker implantation, and tachycardiac rhythm disturbances. Clinical long-term observations of larger patient series and a comparison with conventional forms of therapy are necessary to determine the conclusive therapeutic significance.

Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases

Advances in molecular genetics present new opportunities and challenges for cardiologists who manage patients and families with cardiomyopathies. The aims of this position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases are to review the general issues related to genetic counselling, family screening and genetic testing in families with a cardiomyopathy, and to provide key messages and suggestions for clinicians involved in their management.

One-year follow-up of percutaneous septal ablation for symptomatic hypertrophic obstructive cardiomyopathy in 312 patients: predictors of hemodynamic and clinical response

AimThe aim of this study was to analyze hemodynamic and clinical outcome in a cohort of 312 patients who were followed up over a period of 12 months after alcohol septal ablation (PTSMA) for symptomatic hypertrophic obstructive cardiomyopathy (HOCM).Methods and resultsPTSMA was intended in 337 patients with HOCM (mean age: 54±15 years), with 312 procedures completed by injection of 2.8±1.2 ml of alcohol. In 25 patients (8%) the intervention was aborted, mostly because of contrast echocardiographic findings. In the 312 patients who received alcohol, permanent pacing was necessary in 22 cases (7%); and in-hospital mortality was 1.3% (four patients). During follow-up, contact to six patients (2%) was lost, and three additional patients (1%) died. The 299 patients who either underwent non-invasive reassessment in our institution or transmitted followup data from their local physician formed the study population. Improvement in symptoms was reported by 272 patients (91%). Mean NYHA functional class was reduced from 2.9±0.4 to 1.5±0.7 (p<0.0001) along with a gradient reduction (echo-Doppler) from 59±32 to 8±15 mmHg at rest, and from 120±42 to 28±32 mmHg with provocation (p<0.0001 each). Exercise capacity improved from 94±51 to 119±40 watts (p=0.001), and peak oxygen consumption from 18±4 to 21±6 ml/ kg/min (p=0.01). Younger age and higher outflow gradients at baseline and immediately after intervention were associated with a less favorable hemodynamic outcome. The degree of limitation of exercise capacity at baseline was the only predictor of symptomatic improvement.ConclusionsCatheter-based septal ablation is an effective non-surgical technique for reducing symptoms and outflow gradients in HOCM. In contrast to a previous study, in this cohort of 312 patients there was no association between post-interventional enzyme release and hemodynamic success. Younger patients with high baseline gradients, however, tended to have a less favorable hemodynamic outcome with higher residual gradients.

Long-term follow-up after percutaneous septal ablation in hypertrophic obstructive cardiomyopathy.

ObjectivesThe aim of this study was to evaluate the longterm follow-up results of percutaneous transluminal septal myocardial ablation (PTSMA) in a large patient cohort.BackgroundPTSMA by alcohol injection into septal branches has shown good acute and short-term results in symptomatic patients with hypertrophic obstructive cardiomyopathy.MethodsA total of 100 consecutive symptomatic (NYHA class 2.8 ± 0.6) patients underwent PTSMA. All patients had clinical and non-invasive follow-up at 3 months, 1 year, and annually up to 8 years.ResultsOne patient died at day 2 after intervention due to fulminant pulmonary embolism following deep venous thrombosis, and eight patients required a permanent DDD-pacemaker due to post-interventional complete heart block. Acute reduction of the left ventricular outflow tract gradient was achieved from 76 ± 37 to 19 ± 21 mmHg at rest, from 104 ± 34 to 43 ± 31 mmHg during Valsalva maneuver, and from 146 ± 45 to 59 ± 42 mmHg post extrasystole (p < 0.0001, each). During follow-up (mean follow-up time: 58 ± 14 months), three additional patients died (sudden death at 48 months, non-cardiac death at 49 months and stroke-related death at 60 months after the index procedure). All living patients showed clinical improvement to NYHA-class 1.4 ± 0.6 (after 3 months, n = 99), 1.5 ± 0.6 (after 1 year, n = 99), and 1.6 ± 0.7 at final follow-up (n = 96; p < 0.0001, each). Non-invasive follow-up studies documented ongoing outflow tract gradient reduction, decrease of septal and left ventricular posterior wall thickness, and improvement of exercise capacity.ConclusionsPTSMA is an effective treatment for symptomatic patients with hypertrophic obstructive cardiomyopathy. Follow-up showed ongoing hemodynamic and clinical improvement without increased mortality and morbidity.

Does p.Q247X in TRIM63 Cause Human Hypertrophic Cardiomyopathy

Rationale: Variants in TRIM63, including a nonsense mutation (p.Q247X), have been suggested recently to cause hypertrophic cardiomyopathy. Objective: To verify pathogenicity of TRIM63 p.Q247X detected by whole-exome sequencing in a symptomless professional sports player seeking medical advice because of a prolonged QT interval found during a routine check-up. Methods and Results: Clinical studies were performed in the proband and his mother, who also carried TRIM63 p.Q247X. No evidence of hypertrophic cardiomyopathy was found in either person. Conclusions: The p.Q247X variant in TRIM63 is not likely to be a highly penetrant variant causing hypertrophic cardiomyopathy.

Intraprocedural myocardial contrast echocardiography as a routine procedure in percutaneous transluminal septal myocardial ablation: Detection of threatening myocardial necrosis distant from the septal target area

Percutaneous transluminal septal myocardial ablation (PTSMA) has been introduced as an alternative to surgery for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). Visualization of the ablation area prior to induction of the chemical necrosis is possible by intraprocedural myocardial contrast echocardiography (MCE). We report on two patients in whom MCE showed opacification of the medial papillary muscle or the left ventricular posterolateral free wall. In both patients the correct ablation area could be identified by MCE after a change of the target vessel, thus avoiding potentially fatal complications due to induction of a necrosis of myocardium distant from the septal target area. Cathet. Cardiovasc. Intervent. 47:462–466, 1999.

Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry

AIMS The first cases of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) were published two decades ago. Although the outcomes of single-centre and national ASA registries have been published, the long-term survival and clinical outcome of the procedure are still debated. METHODS AND RESULTS We report long-term outcomes from the as yet largest multinational ASA registry (the Euro-ASA registry). A total of 1275 (58 ± 14 years, median follow-up 5.7 years) highly symptomatic patients treated with ASA were included. The 30-day post-ASA mortality was 1%. Overall, 171 (13%) patients died during follow-up, corresponding to a post-ASA all-cause mortality rate of 2.42 deaths per 100 patient-years. Survival rates at 1, 5, and 10 years after ASA were 98% (95% CI 96-98%), 89% (95% CI 87-91%), and 77% (95% CI 73-80%), respectively. In multivariable analysis, independent predictors of all-cause mortality were age at ASA (P < 0.01), septum thickness before ASA (P < 0.01), NYHA class before ASA (P = 0.047), and the left ventricular (LV) outflow tract gradient at the last clinical check-up (P = 0.048). Alcohol septal ablation reduced the LV outflow tract gradient from 67 ± 36 to 16 ± 21 mmHg (P < 0.01) and NYHA class from 2.9 ± 0.5 to 1.6 ± 0.7 (P < 0.01). At the last check-up, 89% of patients reported dyspnoea of NYHA class ≤2, which was independently associated with LV outflow tract gradient (P < 0.01). CONCLUSIONS The Euro-ASA registry demonstrated low peri-procedural and long-term mortality after ASA. This intervention provided durable relief of symptoms and a reduction of LV outflow tract obstruction in selected and highly symptomatic patients with obstructive HCM. As the post-procedural obstruction seems to be associated with both worse functional status and prognosis, optimal therapy should be focused on the elimination of LV outflow tract gradient.