Early Initiation of Sacubitril/Valsartan in Patients With Acute Heart Failure and Renal Dysfunction: An Analysis of the TRANSITION Study.

BACKGROUND: Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging owing to the risk of further deterioration in renal function, especially after acute decompensated HF (ADHF). METHODS AND RESULTS: We assessed the effect of RD (estimated glomerular filtration rate of ≥30 to <60 mL/min/1.73 m2) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized patients with HFrEF admitted for ADHF (RD, n = 476; non-RD, n = 483). At week 10, the target dose of sacubitril/valsartan (97/103 mg twice daily) was achieved by 42% patients in RD subgroup vs 54% in non-RD patients (P < .001). Sacubitril/valsartan was associated with greater estimated glomerular filtration rate improvements in RD subgroup than non-RD (change from baseline least squares mean 4.1 mL/min/1.73 m2, 95% confidence interval 2.2-6.1, P < .001). Cardiac biomarkers improved significantly in both subgroups; however, compared with the RD subgroup, the improvement was greater in those without RD (N-terminal pro-brain natriuretic peptide, -28.6% vs -44.8%, high-sensitivity troponin T -20.3% vs -33.9%) (P < .001). Patients in the RD subgroup compared with those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%, P < .001), investigator-reported cardiac failure (9.7% vs 5.6%, P = .029), and renal impairment (6.4% vs 2.1%, P = .002). CONCLUSIONS: Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated glomerular filtration rate and cardiac biomarkers. CLINICAL TRIAL REGISTRATION: NCT02661217.

[Diagnosis and treatment of acute ischemic insults]. / Diagnose und Therapie des akuten ischämischen Insults.

In cases of stroke a distinction is made between a transient ischemic attack (TIA), a manifest ischemic infarction and cerebral hemorrhage. Cerebral ischemia can be caused by large vessel disease, small vessel disease, embolic causes, rare causes or stroke of unknown etiology. Acute diagnostic tests include a neurological examination, computed tomography (CT) and/or magnetic resonance imaging (MRI) with angiography, electrocardiography (ECG), and laboratory tests. The basic treatment of patients with TIA or acute ischemic infarction is performed in the stroke unit and includes monitoring of respiratory function, cardiac function, treatment of potential heart failure, detection of swallowing disorders, prophylaxis of thromboembolism, control of blood pressure and elevated blood sugar levels, and lowering of elevated body temperature. In patients with cardioembolic infarction, oral anticoagulation is initiated depending on the severity of the stroke and the size of the stroke on imaging.

Atrial fibrillation is frequent but does not affect risk stratification in pulmonary embolism.

BACKGROUND: Although prior studies indicate a high prevalence of atrial fibrillation (AF) in patients with pulmonary embolism (PE), the exact prevalence and prognostic impact are unknown. METHODS: We aimed to investigate the prevalence, risk factors and prognostic impact of AF on risk stratification, in-hospital adverse outcomes and mortality in 528 consecutive PE patients enrolled in a single-centre registry between 09/2008 and 09/2017. RESULTS: Overall, 52 patients (9.8%) had known AF and 57 (10.8%) presented with AF on admission; of those, 34 (59.6%) were newly diagnosed with AF. Compared to patients with no AF, overt hyperthyroidism was associated with newly diagnosed AF (OR 7.89 [2.99-20.86]), whilst cardiovascular risk comorbidities were more frequently observed in patients with known AF. Patients with AF on admission had more comorbidities, presented more frequently with tachycardia and elevated cardiac biomarkers and were hence stratified to higher risk classes. However, AF on admission had no impact on in-hospital adverse outcome (8.3%) and in-hospital mortality (4.5%). In multivariate logistic regression analyses corrected for AF on admission, NT-proBNP and troponin elevation as well as higher risk classes in risk assessment models remained independent predictors of an in-hospital adverse outcome. CONCLUSION: Atrial fibrillation is a frequent finding in PE, affecting more than 10% of patients. However, AF was not associated with a higher risk of in-hospital adverse outcomes and did not affect the prognostic performance of risk assessment strategies. Thus, our data support the use of risk stratification tools for patients with acute PE irrespective of the heart rhythm on admission.

Automatic Holter electrocardiogram analysis in ischaemic stroke patients to detect paroxysmal atrial fibrillation: ready to replace physicians?

BACKGROUND AND PURPOSE: The detection of paroxysmal atrial fibrillation (pAF) in patients presenting with ischaemic stroke shifts secondary stroke prevention to oral anticoagulation. In order to deal with the time- and resource-consuming manual analysis of prolonged electrocardiogram (ECG)-monitoring data, we investigated the effectiveness of pAF detection with an automated algorithm (AA) in comparison to a manual analysis with software support within the IDEAS study [study analysis (SA)]. METHODS: We used the dataset of the prospective IDEAS cohort of patients with acute ischaemic stroke/transient ischaemic attack presenting in sinus rhythm undergoing prolonged 72-h Holter ECG with central adjudication of atrial fibrillation (AF). This adjudicated diagnosis of AF was compared with a commercially available AA. Discordant results with respect to the diagnosis of pAF were resolved by an additional cardiological reference confirmation. RESULTS: Paroxysmal AF was finally diagnosed in 62 patients (5.9%) in the cohort (n = 1043). AA more often diagnosed pAF (n = 60, 5.8%) as compared with SA (n = 47, 4.5%). Due to a high sensitivity (96.8%) and negative predictive value (99.8%), AA was able to identify patients without pAF, whereas abnormal findings in AA required manual review (specificity 96%; positive predictive value 60.6%). SA exhibited a lower sensitivity (75.8%) and negative predictive value (98.5%), and showed a specificity and positive predictive value of 100%. Agreement between the two methods classified by kappa coefficient was moderate (0.591). CONCLUSION: Automated determination of 'absence of pAF' could be used to reduce the manual review workload associated with review of prolonged Holter ECG recordings.

[Embolic stroke of undetermined source (ESUS) : How much monitoring is necessary?] / ESUS ("embolic stroke of undetermined source") : Wie viel Monitoring ist nötig?

The clinical construct of embolic stroke of unknown source (ESUS) was first described in 2014. It is defined as cryptogenic ischemic stroke after the exclusion of a lacunar infarct, a significant (≥50%) stenosis of extracranial or intracranial arteries and a cardiac source of embolism. Initially, there was hope that these patients would benefit from anticoagulation. This was based on the suspicion that imaging criteria of stroke mimic features of embolism from cardiac sources or the great arteries. In two large randomized trials with 12,600 patients neither rivaroxaban nor dabigatran could reduce the risk of recurrent stroke. Based on these results, current research is focused on paroxysmal atrial fibrillation as a potential cause of stroke in these patients. Several randomized trials could show that by prolongation of monitoring to 30 days atrial fibrillation can be detected in approximately 10% of the patients. Using continuous monitoring (e. g. by implantable loop recorders) atrial fibrillation can even be detected in one quarter of the patients. Not all stroke patients can receive such an intensive monitoring. Therefore, this article summarizes the evidence and presents the resulting recommendations for patient selection and staged rhythm diagnostics and discusses a recently presented algorithm of an expert group for use in daily clinical practice.

[Atrial fibrillation as a comorbidity of heart failure]. / Vorhofflimmern als Komorbidität bei Herzinsuffizienz.

Atrial fibrillation and heart failure are diseases that frequently occur together in patients, and the prevalence of the two diseases will continue to increase in the future. Unfortunately, they exacerbate each other: the prognosis of patients with atrial fibrillation is poorer if there is heart failure, and the prognosis of heart failure patients with atrial fibrillation is poorer than the prognosis of heart failure patients without atrial fibrillation. In the past, studies on drug stabilization of sinus rhythm with antiarrhythmic drugs were not able to show any influence on the prognosis of patients. In these patients, it seems to be better to treat the atrial fibrillation interventionally. The CASTLE-AF study has just shown for the first time that isolation of the pulmonary vein to treat atrial fibrillation in heart failure patients has positive effects: hospital admissions for heart failure decreased and the overall survival improved. Further studies have shown that quality of life improves and performance is increased.

[Acute treatment and secondary prophylaxis of ischemic stroke : An excellent example for personalized medicine]. / Akuttherapie und Sekundärprophylaxe des ischämischen Schlaganfalls : Ein Musterbeispiel für personalisierte Medizin.

About a quarter of a million people in Germany suffer a stroke every year. Stroke is the most dreaded cardiovascular disease, even before myocardial infarction and heart failure. In the last two to three years, significant progress has been made in acute treatment, secondary prophylaxis in patients with patent foramen ovale, and the interdisciplinary evaluation of atrial fibrillation as the cause of the stroke. These new findings allow for more precise treatment.

[Baroreflex activation therapy : Indication and evidence in resistant hypertension and heart failure]. / Barorezeptoraktivierungstherapie : Indikation und Evidenz bei therapieresistenter Hypertonie und Herzinsuffizienz.

Baroreflex activation therapy (BAT) is a sympathoinhibitory procedure for treatment of therapy-resistant hypertension (rsHTN) and severe heart failure with reduced ejection fraction (HFrEF) that been available for several years. The double-blind, randomized Rheos Pivotal Trial demonstrated a blood pressure lowering effect in patients with rsHTN for the first-generation BAT device. A smaller randomized study in heart failure showed that the Barostim Neo system is safe and can improve heart failure symptoms and decrease neuroendocrine activation. However, for this unilateral system, which is currently in clinical use, no data from large randomized trials exist. Despite existing data for BAT in rsHTN and HFrEF, large randomized trials, showing reduction of blood pressure and cardiovascular events are still lacking. Therefore, BAT's efficacy and safety cannot be conclusively assessed.

Automatic detection of paroxysmal atrial fibrillation in patients with ischaemic stroke: better than routine diagnostic workup?

BACKGROUND AND PURPOSE: Prolonged electrocardiogram (ECG) monitoring after ischaemic stroke increases the diagnostic yield of paroxysmal atrial fibrillation (pAF). In order to facilitate the additional workload involved in ECG analysis due to prolonged monitoring times, we investigated the effectiveness of pAF detection with an automated software algorithm (SA) in comparison to the routine staff-based analysis (RA) during standard stroke-unit care. Therefore, patients with acute ischaemic stroke or transitory ischaemic attack presenting with sinus rhythmus on the admission ECG and no history of atrial fibrillation were prospectively included. METHODS: A 24-h Holter ECG assessment was performed using either RA based on a computer-aided evaluation and subsequent review by a cardiologist or a commercially available automated SA. In the case of discordant results concerning the occurrence of pAF between the two methods, the data underwent an independent external rating. RESULTS: Of 809 prospectively enrolled patients, 580 patients fulfilled the inclusion criteria. pAF was ultimately diagnosed in 3.3% of the cohort (19 patients). SA and RA correctly diagnosed pAF in 17 patients resulting in a comparable diagnostic effectiveness of the analysis methods (sensitivity: SA 89.5% vs. RA 89.5%; specificity: SA 99.3% vs. RA 99.1%; κ, 0.686; P < 0.001; 95% confidence interval, 0.525-0.847). RA revealed clinically relevant ECG abnormalities in an additional seven patients. CONCLUSIONS: Although it should not completely replace RA, SA-based evaluation of Holter ECG reaches a high diagnostic effectiveness for the detection of pAF and can be used for a rapid and resource-saving analysis of ECG data to deal with prolonged monitoring times.

[Assessment of subjective physical well-being in heart failure : Validation of the FEW16 questionnaire]. / Erfassung des subjektiven körperlichen Wohlbefindens bei Herzinsuffizienz : Validierung des FEW16-Fragebogens.

INTRODUCTION: Improvement in the quality of life (QoL) is a major goal of therapy for heart failure (HF) patients. Physical well-being as an important component of QoL has not yet been sufficiently covered by disease-specific assessment instruments. The aim of the study was to validate the questionnaire for assessing subjective physical well-being (FEW16) in HF patients with preserved ejection fraction (HFpEF) from the exercise training in diastolic heart failure (Ex-DHF­P) trial. METHOD: A total of 64 HFpEF patients (65 years, 56 % female) were randomized to usual routine treatment with (n = 44) or without training (n = 20). At baseline and 3 months, patients were clinically evaluated and assessed using appropriate questionnaires on the QoL (SF36), physical well-being (FEW16) and depression (PHQ-D). RESULTS: The FEW16 showed good values for Cronbachs' alpha coefficients (0.85-0.93). The cross-validity with SF36 and PHQ-D was highly significant but more so for psychological aspects. At baseline, the FEW16 score correlated with age, the subscale resilience with age and the 6 min walking distance test. At follow-up, the total and resilience scores had improved in the training group. In contrast to the SF36, the FEW16 did not detect differences between the groups in Ex-DHF­P. DISCUSSION: The FEW16 questionnaire showed good internal consistency and correlation with SF36, its total score and resilience had improved after training; however, it did not reflect different changes between the study groups. The FEW16 is therefore more suited to assess general/mental well-being than the subjective physical well-being.

[Invasive treatment of hypertension : Update 2016]. / Interventionelle Hypertonietherapie : Update 2016.

Invasive treatment methods-more specifically renal denervation and baroreceptor activator therapy-have been used for the treatment of therapy-resistant hypertension for several years now. In particular, renal denervation has aroused great interest because it was easy to perform and the first studies provided very promising results. Meanwhile, however, three randomized, blinded studies have been published, and none showed a significant benefit of renal denervation compared to a sham procedure. In addition, in several studies it was demonstrated that intensification of drug therapy, particularly with spironolactone, is at least comparable. Carotid sinus node baroreceptor activator therapy tends to be superior to renal denervation, but the probe currently used is not optimal. The first results by inserting an arteriovenous shunt between the iliac artery and vein are promising, but lack long-term safety data. Currently, all invasive treatment procedures should be performed within the framework of studies or accurate register surveys.

[Interventional strategies in hypertension management]. / Interventionelle Strategien zur Behandlung der Hypertonie.

A number of invasive treatment approaches have become established in the management of severe treatment-resistant hypertension in recent years, including renal denervation and baroreceptor activation therapy. Both methods achieve their antihypertensive effect by influencing the autonomic nervous system. Renal denervation in particular has stimulated considerable interest, since it is simple to perform and initial studies have yielded highly promising results. However, enthusiasm has waned significantly since the initial euphoria. This is due to the fact that the first randomized placebo-controlled double-blind study showed the method to have no significant effect on blood pressure. This experience illustrates the importance of conducting double-blind studies. On the other hand, these results should not lead to renal denervation being shelved. On the contrary, it is worth attempting to improve the treatment and develop criteria to identify which patients it is likely to benefit. Although experience with baroreceptor activation therapy is significantly more limited, similar conclusions can be drawn on it, despite the fact that-in contrast to renal denervation-it achieved a blood pressure reduction of around 10 mmHg in a double-blind study. A potential novel treatment approach lies in creating an arteriovenous shunt between the iliac artery and vein, which has a particularly marked effect on diastolic blood pressure by reducing peripheral resistance. Therapy using brain stimulation of areas in the brainstem region responsible for blood pressure regulation is still at an experimental stage.

Clinical predictors to identify paroxysmal atrial fibrillation after ischaemic stroke.

BACKGROUND AND PURPOSE: Detection of paroxysmal atrial fibrillation (pAF) after an ischaemic cerebrovascular event is of imminent interest, because oral anticoagulation as a highly effective secondary preventive treatment is available. Whereas permanent atrial fibrillation (AF) can be detected during routine electrocardiogram (ECG), longer detection duration will detect more pAF but might be resource consuming. The current study tried to identify clinical predictors for pAF detected during long-term Holter ECG and clinical follow-up. METHODS: Patients with acute ischaemic stroke were prospectively investigated with an intensified algorithm to detect pAF (7-day Holter ECG, follow-up investigations after 90 days and 1 year). RESULTS: Two hundred and eighty-one patients were included, 44 of whom had to be excluded since they presented with permanent AF and another 13 patients had to be excluded due to other causes leaving 224 patients (mean age 68.5 years, 58.5% male). Twenty-nine (12.9%) patients could be identified to have pAF during prolonged Holter monitoring, an additional 13 (5.8%) after follow-up investigations. Multivariate analysis identified advanced age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01-1.08] as well as clinical symptoms >24 h (OR 5.17, 95% CI 1.73-15.48) and a history of coronary artery disease (OR 3.14, 95% CI 1.35-7.28) to be predictive for the detection of pAF. CONCLUSIONS: In acute stroke patients with advanced age, history of coronary artery disease and clinical symptoms >24 h, a prolonged Holter ECG monitoring and follow-up is warranted to identify pAF. This could increase the detection rate of patients requiring anticoagulation and may be able to reduce the risk of recurrent stroke in the case of successful anticoagulation of these patients.

[Function of oesophagus and gastro-oesophageal reflux in patients with cystic fibrosis]. / Funktion der Speiseröhre und gastroösophagealer Reflux bei Patienten mit zystischer Fibrose.

Gastro-oesophageal reflux (GER) has a special meaning for patients with cystic fibrosis (CF). Twelve voluntary patients with CF up to the age of 25 underwent an oesophageal manometry and a 24-hour impedance-pH monitoring. These patients were without symptoms of GER. The examination proved an acid GER in 42 %. In the total population the frequency is ≤ 10 %. In 11 of 12 patients a pathologically low pressure of the lower oesophageal sphincter (LES) was found. No significant correlations between the DeMeester score and the pressure of the LES, the reflux and respiratory symptomatology, the lung function as well as the quality of life could be proven. However, there was a significant correlation between the DeMeester score and the acid clearance time. 37 % of the registered cough pushes were related to a GER, of which 78 % were associated with an acid GER. Therefore, coughing in patients with CF must not necessarily be caused by the underlying disease. The timely detection of a pathological GER in patients with CF, but without symptoms of GER, and its prompt therapy could protect the lung function.

[Diastolic heart failure]. / Diastolische Herzinsuffizienz.

BACKGROUND: Heart failure with preserved ejection fraction (i.e. diastolic heart failure) accounts for about half of heart failure cases. The aim of this review is to reflect current knowledge regarding the epidemiology, pathophysiology and treatment. RESULTS: Diastolic heart failure patients are principally elderly and predominantly female. Numerous pathophysiological alterations in this disease have been shown and recent therapeutic recommendations include control of cardiovascular risk factors and symptoms. New therapeutic options, such as inhibition of late sodium current, aldosterone receptor blockade, combined inhibition of AT1 receptor and the enzyme neprilysin, and phosphodiesterase 5 inhibition are discussed in this review and ongoing clinical trials are also briefly presented. CONCLUSION: Diastolic heart failure remains a cardiac disease which is difficult to treat; however, new study results allow a better definition of a population of patients who could benefit from specific therapies.

[Heart or brain? Problem patients at the interface between cardiology and neurology]. / Herz oder Hirn? Problempatienten an der Schnittstelle zwischen Kardiologie und Neurologie.

A large number of patients fall into a category at the interface between heart or brain and are expected to require thorough clinical knowledge from both the cardiological as well as the neurological point of view for further patient-oriented treatment. The current article therefore addresses this important issue and aims to provide important information for clinical decision making for those patients at the interface between heart and brain. Due to the clinical impact, patients with carotid stenosis, a patent foramen ovale or non-valvular atrial fibrillation are described in more detail in this article.

[Recommendations for the treatment of heart failure : What's new?]. / Empfehlung zur Herzinsuffizienz : Was gibt es Neues?

Treatment escalation of chronic systolic heart failure depends on left ventricular function and symptoms of the patients. In symptomatic patients with severely reduced left ventricular function (ejection fraction ≤ 30 %), the following therapeutic approaches are recommended: (1) angiotensin-converting enzyme (ACE) inhibitors (angiotensin receptor blocker in case of ACE inhibitor intolerance); (2) ß-blockers; (3) mineralocorticoid receptor antagonists; (4) diuretics in case of signs and symptoms of congestion; (5) digitalis, in particular in patients with atrial fibrillation; (6) ivabradine in patients with sinus rhythm and a heart rate ≥ 75/min; (7) an implantable cardioverter defibrillator (ICD); (8) in case of left bundle branch block or wide QRS complex, cardiac resynchronization therapy (CRT; in most cases in combination with an implantable cardioverter defibrillator); (9) intravenous administration of iron in case of iron deficiency; (10) exercise training should be strongly recommended in patients with stable heart failure.

Association of glucose metabolism with diastolic function along the diabetic continuum.

AIMS/HYPOTHESIS: Hyperglycaemia and insulin resistance have been linked to diastolic dysfunction experimentally. We investigated the association between glucose metabolism and diastolic function along the whole spectrum of glucose metabolism states. METHODS: In the observational Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Diastolic Heart Failure (DIAST-CHF) study, patients with risk factors for heart failure were included. We analysed data including comprehensive echocardiography from a subgroup of patients classified by OGTT and history as normal (n = 343), prediabetic (n = 229) and non-insulin treated (n = 335) or insulin-treated (n = 178) type 2 diabetic. RESULTS: While ejection fraction did not differ, markers of diastolic function significantly worsened across groups. Prediabetes represented an intermediate between normal glucose metabolism and diabetes with regard to echocardiography changes. Prevalence and severity of diastolic dysfunction increased significantly (p < 0.001) along the diabetic continuum. Glucose metabolism status was significantly associated with prevalence of diastolic dysfunction on multivariate logistic regression analysis. In the whole cohort, HbA(1c) correlated with early diastolic mitral inflow velocity (E):early diastolic tissue Doppler velocity at mitral annulus (e') ratio (E:e') (r = 0.20, p < 0.001). HbA(1c) was significantly associated with E:e' on multivariate analysis. Similarly, glucose metabolism status was significantly associated with E:e' on multivariate analysis. The distance walked in 6 min decreased along the diabetic spectrum and was significantly correlated with E:e' and grade of diastolic dysfunction. CONCLUSIONS/INTERPRETATION: Glucose metabolism is associated with diastolic dysfunction across the whole spectrum. Our data extend previous observations into the prediabetic and normal range, and may be relevant to preventive approaches, as no effective treatment has been identified for diastolic heart failure once established.

Serial NT-proBNP measurements for risk stratification of patients with decompensated heart failure.

PURPOSE: NT-proBNP is an important prognostic predictor in patients with heart failure. However, it is unknown whether a change of NT-proBNP plasma levels in the early phase of decompensation might be of additional prognostic value in patients with acute decompensation of heart failure. METHODS AND RESULTS: NT-proBNP plasma levels of 116 patients with decompensated heart failure from ischemic/non-ischemic origin were measured at baseline and at 12, 24 and 48 h after hospital admission. Baseline levels and changes of plasma levels within the first 48 h were correlated with 30-day mortality. In all patients, NT-proBNP 12 h after admission was highest and superior with respect to the prediction of 30-day mortality compared to plasma levels on admission. In total, 38 patients died within the first 30 days. In these patients absolute NT-proBNP plasma levels were significantly higher and the increase within 12 h after admission was more pronounced compared to survivors (p<0.001). NT-proBNP at 12 h after admission also had the highest predictive value for the 30-day mortality rate in patients with acute myocardial infarction. The increase of NT-proBNP plasma levels within 12 h after admission had the highest predictive value in patients suffering from decompensated heart failure. CONCLUSIONS: NT-proBNP is a powerful marker of 30-day mortality in patients with decompensated heart failure of ischemic and non-ischemic origin. Compared with single baseline measurements, serial measurements of NT-proBNP plasma levels within 12 h after hospital admission may be used to increase the predictive value of NT-proBNP with regard to the early identification of patients who are at high risk of mortality.

Republished paper: Improving safety culture on adult medical units through multidisciplinary teamwork and communication interventions: the TOPS Project.

AIM: The goal of this project was to improve unit-based safety culture through implementation of a multidisciplinary (pharmacy, nursing, medicine) teamwork and communication intervention. METHOD: The Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture was used to determine the impact of the training with a before-after design. RESULTS: Surveys were returned from 454 healthcare staff before the training and 368 staff 1 year later. Five of eleven safety culture subscales showed significant improvement. Nurses perceived a stronger safety culture than physicians or pharmacists. CONCLUSION: While it is difficult to isolate the effects of the team training intervention from other events occurring during the year between training and postevaluation, overall the intervention seems to have improved the safety culture on these medical units.