The role of non-invasive devices for the telemonitoring of heart failure patients.

Heart failure (HF) patients represent one of the most prevalent as well as one of the most fragile population encountered in the cardiology and internal medicine departments nowadays. Estimated to account for around 26 million people worldwide, diagnosed patients present a poor prognosis and quality of life with a clinical history accompanied by repeated hospital admissions caused by an exacerbation of their chronic condition. The frequent hospitalizations and the extended hospital stays mean an extremely high economic burden for healthcare institutions. Meanwhile, the number of chronically diseased and elderly patients is continuously rising, and a lack of specialized physicians is evident. To cope with this health emergency, more efficient strategies for patient management, more accurate diagnostic tools, and more efficient preventive plans are needed. In recent years, telemonitoring has been introduced as the potential answer to solve such needs. Different methodologies and devices have been progressively investigated for effective home monitoring of cardiologic patients. Invasive hemodynamic devices, such as CardioMEMS™, have been demonstrated to be reducing hospitalizations and mortality, but their use is however restricted to limited cases. The role of external non-invasive devices for remote patient monitoring, instead, is yet to be clarified. In this review, we summarized the most relevant studies and devices that, by utilizing non-invasive telemonitoring, demonstrated whether beneficial effects in the management of HF patients were effective.

Heart failure with mid-range ejection fraction and with preserved ejection fraction.

The annual "heart report" published by the German Heart Foundation (Deutsche Herzstiftung) in December 2017 indicates that heart failure (ICD I50) remains the number one diagnosis of in-hospital-treated patients throughout Germany. For some time, the clinical diagnosis of heart failure has been verified by echocardiographic parameters as well as cardiac biomarkers that assist the clinician to rule in or rule out the presence of a failing heart, when used wisely. By introducing the term "heart failure with mid-range ejection fraction" (HFmrEF), the 2016 European Society of Cardiology (ESC) heart failure guidelines established a third heart failure entity, which was not necessarily seen as an improvement by the heart failure community. Nevertheless, half of all patients suffering from heart failure are now classified as having HFmrEF or heart failure with preserved ejection fraction (HFpEF), but the etiology and treatment options differ substantially. To elucidate this issue, the current review aims to highlight the key findings published to date. This should minimize the confusion that may have been generated by the new term "HFmrEF".

[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.

[Epidemiology and prognosis of heart failure]. / Epidemiologie und Prognose der Herzinsuffizienz.

Heart failure (HF) is a major and growing health problem in western communities. Recent data indicate that more than 50% of patients with the clinical syndrome of HF have a preserved left ventricular ejection fraction (HF with preserved ejection fraction, HFpEF). In contrast to the calculated expectations, the observed incidence of HF is rising. Despite the fact that the relative proportion of patients with preserved left ventricular function is also increasing, other factors, such as ageing of the population and the concomitant change of compound risk factors may also contribute to the actual rise in the incidence of HF. Patients with HF suffer from reduced exercise capacity, impaired quality of life and also from recurrent hospitalization due to HF. Over the past decades, an increase of recurrent HF events has been documented. In contrast to earlier reports in which HFpEF was considered to be more benign than HF with reduced ejection fraction (HFrEF), recent data suggest that once hospitalized for HF, patients with HFpEF and those with HFrEF have a comparable prognosis in terms of morbidity and mortality. Despite increasing clinical and economic relevance, no treatment has yet been shown to convincingly reduce mortality in HFpEF. In contrast, strategies for improving survival have now been established for HFrEF. The problem of HF will continue to be major challenge for the healthcare systems in western communities; therefore, consolidated clinical research is necessary to further improve therapeutic strategies for HFrEF and to generally establish treatment options for HFpEF.

Reverse epidemiology in different stages of heart failure.

BACKGROUND: In heart failure (HF), traditional cardiovascular risk factors (RF) as body mass index (BMI), total cholesterol (TC) and systolic blood pressure (SBP) are associated with better survival. It is unknown at which time point along the disease continuum the adverse impact of these RF ceases and may 'start to reverse'. We analyzed the distribution of RF and their association with survival across HF stages. METHODS: We pooled data from four cohort studies from the German Competence Network HF. Employing ACC/AHA-criteria, patients were allocated to stage A (n=218), B (n=1324), C1 (i.e., New York Heart Association [NYHA] classes I & II; n=1134), and C2+D (NYHA III & IV; n=639). RESULTS: With increasing HF severity median age increased (63/67/67/70 years), whereas the proportion of females (56/52/37/35%), median BMI (26.1/28.8/27.7/26.6 kg/m(2)), TC (212/204/191/172 mg/dl), and SBP (140/148/130/120 mmHg) decreased (P<0.001 for trend for all). In the total cohort, higher levels of all RF were associated with better survival, even after extensive adjustment for multiple confounders. If analyses were stratified, however, a higher RF burden predicted better survival only in clinically symptomatic patients: hazard ratio (HR) per +2 kg/m(2) BMI 0.91 (95% confidence interval 0.88; 0.95); per +10 mg/dl TC 0.93 (0.92; 0.95); per +5 mmHg SBP 0.94 (0.92; 0.95). CONCLUSION: In this well-characterized sample of patients representing the entire HF continuum, reverse associations were only consistently observed in symptomatic HF stages. Our data indicate that the phenomenon of a "reverse epidemiology" in HF is subject to significant selection bias in less advanced disease.

[Exercise training in heart failure]. / Trainingstherapie bei Herzinsuffizienz.

Exercise training in patients with chronic stable heart failure (HF) is a recommended and broadly accepted treatment strategy that is an integral part of an evidence-based management involving pharmacological and non-pharmacological therapies. There is ample scientific evidence that exercise training in HF with reduced (HFrEF) and with preserved ejection fraction (HFpEF) improves exercise capacity, HF symptoms and quality of life. This is due to an improvement of central hemodynamics, endothelial function, neurohumoral activation, skeletal muscle structure and function as well as a decrease in inflammatory markers. The largest randomized, controlled HF-ACTION study (Heart Failure-A Controlled Trial Investigating Outcomes of exercise TraiNing) demonstrated that exercise training results in a modest improvement of all-cause mortality and hospitalizations in HFrEF, depending on adequate compliance. Outcome data in HFpEF are lacking. Besides compliance, efficacy of exercise training is dependent on the intensity and type of exercise. Resistance and high intensity endurance training in addition to a standard aerobic exercise seem to be superior in improving the clinical status of HF patients. In the future, individualized exercise programs will help to improve long-term adherence to exercise training.

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.

[Exercise training in heart failure]. / Körperliches Training bei Herzinsuffizienz.

In patients with chronic but stable heart failure (HF) exercise training is a recommended and widely accepted adjunct to an evidence-based management involving pharmacological and non-pharmacological therapies. Various pathophysiological mechanisms, such as central hemodynamics, vasculature, ventilation, skeletal muscle function as well as neurohormonal activation and inflammation are responsible for exercise intolerance described in HF patients. There is sufficient and growing evidence that exercise training in HF with reduced (HFrEF) and with preserved ejection fraction (HFpEF) is effective in improving exercise capacity, HF symptoms and quality of life. The positive effects of exercise training in HF are mediated by an improvement of central hemodynamics, endothelial function, inflammatory markers, neurohumoral activation, as well as skeletal muscle structure and function. In contrast to convincing data from a large meta-analysis, the large HF-ACTION study (Heart Failure-A Controlled Trial Investigating Outcomes of exercise TraiNing) only demonstrated a modest improvement of all cause mortality and hospitalizations in HFrEF. Outcome data in HFpEF are lacking. Whether interval training incorporating variable and higher intensities or the addition of resistance exercise to a standard aerobic prescription is superior in improving clinical status of HF patients is currently being examined. Despite increasing validation of the potential of exercise training in chronic HF, challenges remain in the routine therapeutic application, including interdisciplinary management, financing of long-term exercise programs and the need to improve short-term and long-term adherence to exercise training.

[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.

Impact of the ß1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients.

This pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS-ELD trial determined the impact of the ß1-adrenoceptor Arg189Gly polymorphism on heart-rate responses to bisoprolol or carvedilol in elderly patients with heart failure (421 with sinus rhythm, 107 with atrial fibrillation). Patients were randomized 1:1 to bisoprolol or carvedilol with a fortnightly dose-doubling scheme and guideline target doses. Patients with sinus rhythm responded essentially identically to bisoprolol and carvedilol, independent of genotype. Atrial fibrillation patients homozygous for Arg389 had a much smaller response to carvedilol than carriers of at least one Gly389 allele (mean difference 12 bpm, P < 0.00001). Carvedilol up to 2 × 12.5 mg did not reduce heart rate in Arg389Arg homozygotes at all. Interestingly, the immediate response to carvedilol did not differ between genotypes. The Arg389Gly polymorphism has a major impact on the heart-rate response to carvedilol (but not bisoprolol) in patients with heart failure plus atrial fibrillation.

[Neurohormonal activation and maximal exercise capacity in diastolic dysfunction and diastolic heart failure]. / Neurohumorale Aktivierung und maximale Leistungsfähigkeit bei diastolischer Dysfunktion und diastolischer Herzinsuffizienz.

BACKGROUND: Patients with diastolic dysfunction (DD) and diastolic heart failure (DHF) are known to suffer from reduced exercise capacity. However, there is only limited knowledge about the mechanisms involved in the development of exercise intolerance. This study was designed to investigate the direct association between neurohumoral activation and maximal exercise capacity in patients with diastolic dysfunction and diastolic heart failure and its dependency of parameters of diastolic function and clinical characteristics. METHODS: 54 patients (LVEF ≥ 50 %) with echocardiographically proven DD were prospectively included. Patients were divided into having DD or DHF according to NYHA functional class at presentation (NYHA I: DD; NYHA ≥ II: DHF). All patients underwent physical examination including medical history, comprehensive echocardiography with detailed measurement of diastolic function, spiroergometry and blood sampling under standardized conditions. RESULTS: Exercise capacity was significantly reduced in patients with DHF (peakVO2 DD (30,5 ± 8,4 ml/kg/min) vs. DHF (15,7 ± 3,5 ml/kg/min) p < 0,001). N-terminal pro brain natriuretic peptide (NT-proBNP) was significantly higher in patients with DHF (DD 49,4 pg/ml [range 17,5 - 96,1] vs. DHF 285,3 pg/ml [190,4 - 426,0], p < 0,001). E/é ratio was not significantly different between groups (DD 11,3 ± 3,3 vs. DHF 12,9 ± 3,7, n. s.), in contrast to left atrial volume index (LAVI): DD 23,4 ± 5,9 ml/m² vs. DHF 29,6 ± 8,4 ml/m², p = 0,017). In bivariate correlation analyses age (r = -0,477, p < 0,001) gender (r = -0,418, p = 0,002) and NT-proBNP (r = -0,488, p < 0,001) were significantly related to peakVO2, whereas LAVI (r = 0,106, p = 0,641) or E/é (r = 0,107, p = 0,441) were not. In multiple regression analyses, after adjustment for body mass index, E/é and LAVI, the association of NT-proBNP and peakVO2 was independent of age and gender (p = 0,001). CONCLUSION: NT-proBNP was siginificantly and independent of age and gender correlated to maximal exercise capacity, whereas resting diastolic function did not. Echocardiographically determined diastolic function is a prerequisite for the diagnosis of diastolic heart failure, but elevated NT-proBNP may rather play a key role in the development of signs and symptoms in these patients.

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.

f-Element disiloxanediolates: novel Si-O-based inorganic heterocycles.

The preparation and structural characterization of scandium and f-element complexes derived from the disiloxanediolate dianion, [(Ph2SiO)2O]2-, are reported. Reactions of in situ prepared Ln[N(SiMe3)2]3 (Ln = Eu, Sm, Gd) with (Ph2SiOH)2O in different stoichiometries afforded the lanthanide disiloxanediolates [Eu[[(Ph2SiO)2O]Li(Et2O)]3] (1), [[[(Ph2SiO)2O]Li(dme)]2SmCl(dme)] (2), and [[[((Ph2SiO)2O]Li(thf)2]2GdN(SiMe3)2] (3). In situ formed (Ph2SiOLi)2O reacted with anhydrous NdBr3 (molar ratio 3:1) to give polymeric [[Nd[(Ph2SiO)2O]3[mu-Li(thf)]2[mu2LiBrLi(thf)(Et2O)]]n] (4). Treatment of 3 with Ph2Si(OH)2 in the presence of acetonitrile yielded the dilithium trisiloxanediolate derivative [[Ph2Si(OSiPh2O)2][Li(MeCN)]2]2 (5), which according to an X-ray analysis displays an Li4O4 heterocubane structure. The trinuclear scandium complex [[[(Ph2SiO)2O]Sc(acac)2]2Sc(acac)] (6) was obtained by reaction of [(C5Me5)Sc(acac)2] (C5Me5 = eta5-pentamethylcyclopentadienyl) with (Ph2SiOH)2O in a 3:2 molar ratio. Selective formation of the colorless uranium(VI) derivative [U[Ph2Si(OSiPh20)2]2[(Ph2SiO)2O]] (7) was observed when uranocene, U(eta8-C8H8)2, was allowed to react with (Ph2SiOH)2O. An X-ray diffraction study of the solvated derivative [U[Ph2Si(OSiPh2O)2]2[(Ph2SiO)2O]].Et2O.TMEDA (TMEDA= N,N,N',N'-tetramethyl-ethylenediamine) (7a) revealed the presence of both the original [(Ph2SiO)2O]2- dianion as well as the ring-enlarged [Ph2Si(OSiPh2O)2]2- ligand in the same molecule.