The Heart Failure Optimization Study (HF-OPT): rationale and design.

BACKGROUND: According to the current guidelines, implantable cardioverter-defibrillators (ICD) for primary prevention in patients with heart failure and reduced ejection fraction (HFrEF) should not be considered until optimal guideline-directed medical therapy (GDMT) has been achieved for a minimum of 3 months. Optimization of GDMT often needs time beyond 3 months after diagnosis. The aim of the Heart Failure Optimization Study (HF-OPT) is to evaluate the recovery of left ventricular function beyond 3 months after diagnosis of newly diagnosed HFrEF. METHODS: The HF-OPT multicenter study is comprised of two non-randomized phases (registry and study). During the first 90 days a wearable cardioverter-defibrillator (WCD) is prescribed and patients are enrolled in an observational pre-study registry. Registry subjects meeting inclusion criteria for the study portion at day 90 have ongoing left ventricular ejection fraction (LVEF) reassessment at 90, 180 and 360 days after the index hospital discharge, regardless of continued WCD use. Approximately 600 subjects will be enrolled in the study portion. Of those, one-third are anticipated to start the study phase at day 90 with reduced LVEF. The primary objective of this study is to observe the rate of recovery of LVEF > 35% between 90 and 180 days, while key secondary endpoints include mortality and WCD recorded arrhythmias and shocks. DISCUSSION: The HF-OPT study will provide important information on the rate of additional recovery of LVEF > 35%, between 90 and 180 days, in newly diagnosed HF with reduced LVEF patients being titrated with GDMT. The results of the study may impact indications for primary prophylactic ICD implantation.

Dilated cardiomyopathies and non-compaction cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and one of the most common causes of heart failure. It is characterized by left or biventricular dilation and a reduced systolic function. The causes are manifold and range from myocarditis to alcohol and other toxins, to rheumatological, endocrinological, and metabolic diseases. Peripartum cardiomyopathy is a special form that occurs at the end of or shortly after pregnancy. Genetic mutations can be detected in approximately 30-50% of DCM patients. Owing to the growing possibilities of genetic diagnostics, increasingly more triggering variants and hereditary mechanisms emerge. This is particularly important with regard to risk stratification for patients with variants with an increased risk of arrhythmias. Patient prognosis is determined by the occurrence of heart failure and arrhythmias. In addition to the treatment of the underlying disease or the elimination of triggering harmful toxins, therapy consists in guideline-directed heart failure treatment including drug and device therapy.

[Multipoint pacing-more CRT or a waste of battery power?] / MultiPoint-Pacing ­ mehr CRT oder Batterieverschwendung?

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with broad QRS complex ≥130 ms and heart failure with reduced ejection fraction despite optimal guideline-directed medical therapy. However, approximately 30% of the patients implanted with a CRT system do not show clinical benefit. Reasons for nonresponse are complex and some aspects can be addressed during follow-up. Based on quadripolar lead technology, multipoint pacing (MPP) allows left ventricular stimulation at two different sites along the lead. In particular, in scarred and fibrotic ventricular myocardium stimulation at two different sites may overcome conduction barriers and lead to homogeneous ventricular depolarization. Especially for patients that do not respond to conventional CRT, activation of MPP may present an option to increase clinical response. On the other hand, MPP may significantly decrease battery longevity.This review offers an overview of the current knowledge and data on MPP balancing the potential clinical benefit and the possible disadvantages of this therapy.

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

[Ventricular arrhythmias : What has been confirmed in therapy?] / Ventrikuläre Herzrhythmusstörungen : Was ist gesichert in der Therapie?

Ventricular arrhythmias include a wide range of potentially benign single ventricular premature contractions to ventricular tachycardia and ventricular fibrillation with a risk for sudden cardiac death. The diagnosis of ventricular arrhythmia is made by 12-lead electrocardiogram, 24 h Holter monitoring, an external or implantable loop recorder, or during in-hospital monitoring. Especially the diagnosis of wide complex tachycardias is challenging in terms of differentiating between ventricular tachycardia and supraventricular tachycardia with aberrant atrioventricular conduction. After documentation of ventricular arrhythmias, diagnostic work-up with respect to structural or electrical cardiomyopathy is mandatory followed by risk stratification for sudden cardiac death. Therapeutic options for treatment of ventricular arrhythmias range from pharmacological therapy and interventional procedures such as catheter ablation and implantable devices. The current article provides an overview of the diagnosis of ventricular tachycardia and underlying cardiomyopathies. Furthermore, medical and interventional therapies are described. In addition, the indications for implantable and wearable defibrillators are presented.

[The wearable cardioverter/defibrillator : Temporary protection from sudden cardiac death]. / Die Defibrillatorweste : Passagerer Schutz vor dem plötzlichen Herztod.

In the majority of cases sudden cardiac death (SCD) is caused by ventricular tachyarrhythmia. Implantable cardioverter-defibrillators (ICD) represent an evidence-based and established method for prevention of SCD. For patients who do not fulfill the criteria for guideline-conform implantation of an ICD but still have an increased, e.g. transient risk for SCD, a wearable cardioverter-defibrillator (WCD) vest was developed to temporarily prevent SCD. Numerous studies have shown the safety and efficacy of the WCD, although there is still a gap in evidence concerning a reduction in overall mortality and improvement in prognosis. This article gives an overview on the currently available literature on WCD, the indications, potential risks and complications.

[Primary and secondary prophylactic ICD therapy in congenital electrical and structural cardiomyopathies]. / ICD-Therapie zur Primär- und Sekundärprophylaxe kongenitaler arrhythmogener Erkrankungen.

Congenital electrical and structural cardiomyopathies are rare and associated with an increased risk for syncope and sudden cardiac death in the young. Due to the young age of the patients and the limited data available, risk stratification and especially ICD therapy are challenging. In this young patient collective, ICD therapy is associated with a high complication rate, which does not justify unreserved primary prophylactic ICD implantation. The aim of this review is to elucidate risk stratification and ICD therapy of various electrical and structural cardiomyopathies.

Clinical evaluation and risk stratification in patients with syncope.

Syncope accounts for approximately 1 % of visits to emergency departments. The first diagnostic step is to rule out nonsyncopal conditions as a cause of the transient loss of consciousness. Next, the basic clinical evaluation should identify patients at high risk for potentially life-threatening events. These patients should be admitted and monitored until a diagnosis is made and definitive treatment can be offered. Guided by the basic evaluation findings, specific tests should be performed to prove or rule out the suspected diagnosis. In low-risk patients, this should preferably be done in an outpatient setting. To date, there is no consensus on a structured algorithm for the evaluation of patients with syncope. Therefore, it seems beneficial to formulate an algorithm based on the current guidelines for the management of syncope for use in the clinical setting.

[Short QT syndrome]. / Short-QT-Syndrom.

Short QT syndrome was first described in 2000. It is a sporadic or familial ion channel disease that is associated with abbreviation of the QT interval permanently or transiently. The time of first manifestation of symptoms such as atrial fibrillation or syncope or even sudden death is between the 2nd and 4th decade. Sudden death has also been described for newborns and adolescents. Therapy depends on the severity of the symptoms. The therapy of choice for secondary prevention of sudden death is the implantable cardioverter-defibrillator (ICD). Quinidine has been shown to be effective in preventing arrhythmias in a number of patients. It is mostly used as an adjunct to the ICD but has also been used with considerable success in children and individuals who refused ICD implantation.

Insights into the location of type I ECG in patients with Brugada syndrome: correlation of ECG and cardiovascular magnetic resonance imaging.

BACKGROUND: Brugada syndrome is characterized by ST-segment abnormalities in V1-V3. Electrocardiogram (ECG) leads placed in the 3rd and 2nd intercostal spaces (ICSs) increased the sensitivity for the detection of a type I ECG pattern. The anatomic explanation for this finding is pending. OBJECTIVE: The purpose of the study was to correlate the location of the Brugada type I ECG with the anatomic location of the right ventricular outflow tract (RVOT). METHODS: Twenty patients with positive ajmaline challenge and 10 patients with spontaneous Brugada type I ECG performed by using 12 right precordial leads underwent cardiovascular magnetic resonance imaging (CMRI). The craniocaudal and lateral extent of the RVOT and maximal RVOT area were determined. Type I ECG pattern and maximal ST-segment elevation were correlated to extent and maximal RVOT area, respectively. RESULTS: In all patients, Brugada type I pattern was found in the 3rd ICS in sternal and left-parasternal positions. RVOT extent determined by using CMRI included the 3rd ICS in all patients. Maximal RVOT area was found in 3 patients in the 2nd ICS, in 5 patients in the 4th ICS, and in 22 patients in the 3rd ICS. CMRI predicted type I pattern with a sensitivity of 97.2%, specificity of 91.7%, positive predictive value of 88.6%, and negative predictive value of 98.0%. Maximal RVOT area coincided with maximal ST-segment elevation in 29 of 30 patients. CONCLUSION: RVOT localization determined by using CMRI correlates highly with the type I Brugada pattern. Lead positioning according to RVOT location improves the diagnosis of Brugada syndrome.

[Orthostatic hypotension : diagnosis and therapy]. / Orthostatische Hypotension : Diagnostik und Therapie.

Syncope is a frequent clinical event in the general population and occurs in up to every second patient during their lifetime. Reflex syncope is the most prevalent mechanism and is often triggered by orthostatic stress. Orthostatic hypotension (OH) represents a rare cause in young patients but is an important differential diagnosis in the aged. The Framingham study revealed an increase in the incidence of OH-triggered syncope from 5.7 events/1000 person-years at the age of 60-69 to 11.1 in men who are 70-79 years of age. OH often constitutes a chronic, debilitating illness with significant reduction in the quality of life. Important causes are volume loss, side effects of different vasoactive drugs, and neurodegenerative or secondary autonomic diseases following long-standing diabetes or amyloid disease. OH is difficult to treat. The therapeutic goal is to improve postural symptoms, standing time, and prevention of syncopal events. Drug therapy alone is never adequate. Because orthostatic stress varies during the day, a patient-tailored approach that emphasizes education and several general actions is recommended together with physical therapy and isometric exercise maneuvers. Moderate and severe cases require additional drug treatment to increase peripheral vascular resistance.

Arrhythmogenic hereditary syndromes: Brugada Syndrome, long QT syndrome, short QT syndrome and CPVT.

In approximately 10-20% of all sudden deaths no structural cardiac abnormalities can be identified. Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome and catecholaminergic polymorphic ventricular tachyarrhythmias. Each of these cardiac channelopathies is charaterized by unique genetic and clinical features. The resting ECG and the ECG under exercise are pivotal for the diagnosis of ion channel diseases. Molecular genetic screening can reveal underlying mutations in a variable degree among the cardiac ion channel diseases in up to 70% (LQTS) and may identify individuals with incomplete penetration of the disease. In patients with primary electrical diseases specific clinical triggers for arrhythmic events such as syncope or sudden cardiac death have been identified including exercise, strenuous activity, auditory stimuli or increased vagal tone. The significance of programmed ventricular stimulation is at present unclear concerning risk stratification in patients with Brugada syndrome and short QT syndrome and of no significance in long QT syndrome and catecholaminergic polymorphic ventricular tachycardias. The success of medical therapy remains modest for prevention of sudden cardiac death and may necessitate the insertion of an implantable cardioverter. However, side effects with inappropriate therapies in this patient group with often young and active individuals have to be encountered. More insights into the arrhythmogenesis is critical for future development of effective medical treatment strategies.

Evaluation and management of syncope.

Syncope is a common symptom and accounts for approximately 1% of all emergency visits. There are four main causes of syncope: reflex, neurally mediated syncope, orthostatic hypotension and cardiac syncope. The prognosis of patients with reflex syncopes is good, whereas patients with cardiac syncope are at increased risk for sudden cardiac death. The first diagnosic step after transient loss of consciousness the diagnosis syncope has to be established. It has to be differentiated from other forms of loss of consciousness according to current definition. Careful evaluation of the patient with syncope is mandatory. If the underlying cause of syncope can be diagnosed during initial evaluation, the patient should be treated accordingly. If the cause of syncope remains unclear, the patient has to be stratified with respect to the risk of a cardiovascular event and sudden cardiac death and further evaluation initiated. This review gives a comprehensive summary of definition, work-up and treatment of syncope based on the current guidelines for the evaluation of syncope.

Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry.

BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. METHODS AND RESULTS: Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. CONCLUSIONS: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.

[Magnetic navigation in invasive electrophysiological diagnostic and therapy]. / Magnetische Navigation in der elektrophysiologischen Diagnostik und Therapie.

Electrophysiological stimulation and ablation is currently performed with manually deflectable catheters of different lengths and curves. Disadvantages of conventional therapy are catheter stiffness, limited local stability, risk of dislocation or perforation, and reduced tissue contact in regions with difficult access. Fluoroscopy to control catheter movement and position may require substantial radiation times. Magnetic navigation was first applied for right heart catherization in congenital heart disease in 1991; the first electrophysiological application took place in 2003. Today, an ablation electrode with small magnets is aligned in the patient's heart by two external magnets positioned at both sides of the thorax. Antegrade and retrograde movement of the distal catheter tip are performed via an external device on the patient's thigh. Three-dimensional MRI scans acquired before intervention can be merged with electroanatomical reconstruction, leading to further reductions of radiation burden. During treatment of supraventricular tachyarrhythmias high local precision of magnetically guided catheters, good local stability, and a substantially reduced radiation time have been reported. First applications in ventricular tachyarrhythmias and complex congenital cardiac defects indicate a comparable effect. Limitations of this therapy are the application in left atrial procedures (open irrigated ablation catheters not yet available), difficult transaortic retrograde approach (high lead flexibility), and the considerable costs. Magnet-assisted navigation is feasible during percutaneous coronary interventions of tortuous coronary arteries and in positioning guidewires in coronary sinus side branches for resynchronisation therapy. Future applications will be complex left atrial procedures, magnetically guided cardiac stem cell therapy, local drug application, and extracardiac vessel therapy.