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Implanted cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs) are established interventions that prolong life in advanced heart failure, but their combination has not been demonstrated as beneficial. Electromagnetic interference (EMI) produced by a LVAD can preclude ICD interrogation with external programmers. We undertook a systematic evaluation of the LVAD-ICD interaction "in-vitro" to clarify the extent of this interaction.Using explanted ICDs and VADs in a mock physiological rig, we assessed interrogation and reprogramming of ICD devices in the presence of a running LVAD. When connectivity between the ICD programmer and the ICD failed, we attempted three different techniques to re-establish connectivity: (1) Electromagnetic shielding of the ICD with a pseudo-faraday cage; (2) altering the LVAD speed; and (3) increasing the distance between the VAD and the ICD.We tested a total of 24 ICDs from different manufacturers in the presence of the Heartware (HW) and HeartMate 3 (HM3) LVADs. With HW, we only observed interaction with Biotronik ICD devices at very close range (0-6 cm). With HM3, only Medtronic ICD devices showed no interaction. Interactions could be mitigated by increasing the VAD-ICD distance.LVADs, notably the HM3, produce EMI that interferes with the communication between an ICD and its respective programmer. This may need to be considered when choosing the type of VAD to implant in patients with a previously implanted left-sided ICD. The only safe way to regain connectivity is to increase the distance between the VAD and the ICD, with patients raising their arm above their head.

BACKGROUND Driveline infections (DLIs) at the exit site are frequent in patients with left ventricular assist devices (LVADs). The dynamics from colonization to infection are yet to be investigated. We combined systematic swabbing at the driveline exit site and genomic analyses to study the dynamics of bacterial pathogens and get insights into DLIs pathogenesis. METHODS A prospective, observational, single-centre cohort study at the University Hospital of Bern, Switzerland was performed. Patients with LVAD were systematically swabbed at the driveline exit site between June 2019 and December 2021, irrespective of signs and symptoms of DLI. Bacterial isolates were identified and a subset was whole-genome sequenced. RESULTS Fifty-three patients were screened, of which 45 (84.9%) were included in the final population. Bacterial colonization at the driveline exit site without manifestation of DLI was frequent and observed in 17 patients (37.8%). Twenty-two patients (48.9%) developed at least one DLI episode over the study period. Incidence of DLIs reached 2.3 cases per 1,000 LVAD days. The majority of the organisms cultivated from exit sites were Staphylococcus species. Genome analysis revealed that bacteria persisted at the driveline exit site over time. In four patients, transition from colonization to clinical DLI was observed. CONCLUSION Our study is the first to address bacterial colonization in the LVAD-DLI setting. We observed that bacterial colonization at the driveline exit site was a frequent phenomenon, and in a few cases it preceded clinically relevant infections. We also provided acquisition of hospital-acquired multidrug-resistant bacteria and the transmission of pathogens between patients.

Low flow alarms represent a management challenge in patients with left ventricular assist devices because they are often a consequence of complex patient-device interactions. We present a case of intermittent suction of the postero-medial papillary muscle into the left ventricular assist device inflow cannula during diastole, causing low flows. This case highlights the importance of a systematic approach and use of multiple investigation modalities in making an accurate diagnosis. (Level of Difficulty: Advanced.), Central Illustration

The number of patients treated by ventricular assist devices (VAD) and the duration of VAD treatment is increasing. One of the main complications in terms of morbidity and mortality for VAD patients are microbial infections. With this study, we aimed to investigate the epidemiology and microbiological characteristics of infections occurring in a VAD population to identify modifiable factors.We retrospectively analyzed patient characteristics, treatments and outcomes of VAD-specific/related infections. All patients implanted in our institution with a continuous flow VAD between January 2009 and January 2019 were included. Risk factors for VAD infection were assessed using simple and multiple linear regressions.Of the 104 patients screened, 99 were included in the analysis, the majority of which were men (78%). At implantation, the mean age was 56 years and the median time on VAD support was 541 days. The overall infection rate per year per patient was 1.4. Forty-seven patients (60%) suffered from VAD-specific/related infection. Half of all infection episodes occurred in the first 4 months but the proportion of VAD-specific/related infection was higher after the first 4 months (74% of all infection). Using regression models, no patient specific risk factors were associated with VAD-specific/related infections.No predictive factors for infection during VAD support were identified in this study. By extension, diabetes, renal insufficiency, age or high BMI are not sufficient to deny a patient access to ventricular support.

INTRODUCTION Ventricular function in elderly patients with aortic stenosis is impeded both by restricted aortic flow and arterial stiffening. A number of patients continue to have exertional intolerance after relief of aortic valvular obstruction due to unrecognized ventriculo-arterial coupling mismatch. HYPOTHESIS Quantification of valvulo-arterial load (VAL), using a simultaneous applanation tonometry/cardiac magnetic resonance (CMR) technique, can accurately assess the relative contributions of aortic stiffness and valve gradient in older patients with aortic stenosis. METHODS Elderly patients with aortic stenosis underwent a simultaneous applanation tonometry/CMR protocol. CMR provided left ventricular volume and aortic flow simultaneously with radial applanation tonometry pressure acquisition. Central aortic pressure was derived by transformation of the radial applanation tonometry waveform. VAL was determined as the relationship of derived aortic pressure to CMR aortic flow in frequency domain (central illustration). RESULTS Twenty patients (age 80 ± 9 years; 12 males; blood pressure 140/75 ± 20 mmHg) with aortic stenosis on transthoracic echocardiogram (16 severe; mean gradient 45 ± 16 mmHg; aortic valve area 0.8 ± 0.2 cm2) were enrolled. Derived aortic pressure and flow waveforms correlated well with invasive data. Increased VAL was significantly associated with advanced age (P = 0.04) and raised SBP (P

BACKGROUND The aim of this study was to validate our previous finding that frailty predicts early mortality in patients with advanced heart failure (AHF) and that including cognition in the frailty assessment enhances the prediction of mortality. METHODS Patients with AHF referred to our Transplant Unit between November 2015 and April 2020 underwent physical frailty assessment using the modified Fried physical frailty (PF) phenotype as well as cognitive assessment using the Montreal Cognitive Assessment (MOCA) to identify patients who were cognitively frail (CogF). We assessed the predictive value of the 2 frailty measures (PF ≥ 3 of 5 = frail; CogF ≥ 3 of 6 = frail) for pretransplant mortality. RESULTS 313 patients (233 male, 80 female; age 53 ± 13 years) were assessed. Of these, 224 patients (72%) were nonfrail and 89 (28%) were frail using the PF. The cognitive frailty assessment identified an additional 30 patients as frail: 119 (38%). Frail patients had significantly increased mortality as compared to nonfrail patients. Ventricular assist device and heart transplant-censored survival at 12 months was 92 ± 2 % for nonfrail and 69 ± 5% for frail patients (p < 0.0001) using the CogF instrument. CONCLUSIONS This study validates our previously published findings that frailty is prevalent in patients with advanced heart failure referred for heart transplantation. Physical frailty predicts early mortality. The addition of cognitive assessment to the physical assessment of frailty identifies an additional cohort of patients with a similarly poor prognosis.

BACKGROUND: Frailty is associated with adverse outcomes in advanced heart failure. We studied the impact of frailty on postoperative outcomes in bridge to transplant (BTT) durable mechanical circulatory support (MCS) recipients. METHODS: Patients undergoing left ventricular assist device (LVAD, n = 96) or biventricular support (BiV, n = 11) as BTT underwent frailty assessment. Frailty was defined as ≥ 3 physical domains of the Fried's Frailty Phenotype (FFP) or ≥ 2 physical domains of the FFP plus cognitive impairment on the Montreal Cognitive Assessment (MoCA). RESULTS: No difference in mortality at 360 days was observed in frail (n = 6/38, 15.8%) vs non-frail (n = 4/58, 6.9%) LVAD supported patients, p = 0.19. However, there was a significant excess mortality in frail BiV (n = 4/5) vs non-frail BiV (n = 0/6) supported patients, p = 0.013. In all patients, frail patients compared to non-frail patients experienced longer intensive care unit stay, 12 vs 6 days (p < 0.0001) and hospital length of stay, 48 vs 27 days (p < 0.0001). There was no difference in hemocompatibility and infection related adverse events. The majority (n = 22/29, 75.9%) of frail patients became non-frail following MCS; contrastingly, a minority (n = 3/42, 7.1%) became frail from being non-frail (p = 0.0003). CONCLUSIONS: Abnormal markers of frailty are common in patients undergoing BTT-MCS support and those used herein predict mortality in BiV-supported patients, but not in LVAD patients. These findings may help us better identify patients who will benefit most from BiV-BTT therapy.

BACKGROUND Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx. METHODS We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF). RESULTS Post-transplant survival rates for the NF cohort at 1 and 12 months were 97% (93–100) and 95% (91–99) (95% CI), respectively. In contrast, post-transplant survival rates for the F cohort at the same time points were 86% (76–96) and 74% (60–84) (p < 0.0008 vs NF cohort), respectively. The Cox proportional hazards regression analysis demonstrated that pre-transplant frailty was an independent predictor of post-transplant mortality with a hazard ratio of 3.8 (95% CI: 1.4–10.5). Intensive care unit and hospital length of stay were 2 and 7 days longer in the F cohort (both p < 0.05), respectively, than in the NF cohort. CONCLUSIONS Frailty within 6 months before HTx is independently associated with increased mortality and prolonged hospitalization after transplantation. Future research should focus on the development of strategies to mitigate the adverse effects of pre-transplant frailty.

The use of continuous-flow ventricular assist devices (cf-VAD) necessitates systemic anticoagulation, routinely with vitamin K antagonists (VKA). Newer direct oral anticoagulants (DOACs) have significant advantages over VKA in providing a predictable level of systemic anticoagulation without frequent monitoring or strict dietary surveillance. Despite randomized evidence demonstrating their usefulness in several conditions including atrial fibrillation, there is limited data pertaining to their use in cf-VAD patients. Early reports of adverse outcomes has resulted in a Class III recommendation, advising against DOACs generally in cf-VAD patients. Recent reports suggest there may be a role for certain DOACs; as such we present a systematic review identifying studies reporting DOAC uses in patients with a cf-VAD. We identified eight pertinent studies, including a single randomized controlled trial and seven case reports/series. Limited numbers and significant study heterogeneity limits interpretation; however, Factor Xa inhibitors appear to be feasible alternatives, favorable to direct thrombin inhibitors, although further research is required.

Pharmacological therapy of heart failure with reduced ejection fraction Abstract. Pharmacological therapy for heart failure has made great progress over the last three decades and evidence-based therapies have significantly improved survival and quality of life. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers are the cornerstone of the heart failure therapy; indicated in virtually every patient with heart failure and reduced ejection fraction. As soon as the left ventricular ejection fraction decreases below 35 % and / or symptoms are still present (NYHA II-IV), a mineralocorticoid receptor antagonist should be added. A rather recent addition to current heart failure therapy with convincing data is the substance combination sacubitril / valsartan. It is indicated for patients with persistent symptomatic heart failure despite optimal medical therapy with ACE inhibitors or ARBs, beta-blockers, and MRAs. Crucial for all mentioned substances is to aim for the maximal tolerated dose. Various additional therapies have no proven survival benefit but are important for symptom control in everyday life. Above all the diuretics, where loop diuretics show a better effect profile compared to thiazide diuretics. Furthermore, achieving an optimal iron status (the limit to start a substitution is significantly higher than in patients without heart failure), decreasing the heart frequency with Ivabradine (if heart rate persists above 70 / min despite fully dosed betablocker) and «lifestyle changes» can add to the success of the medical treatment. The importance of digoxin has been steadily decreasing. The previously advocated therapeutic anticoagulation in patients with severely reduced LVEF is not propagated anymore. Significant arrhythmias (especially atrial fibrillation and ventricular arrhythmias) are common in advanced diseases. In addition to beta-blockers, amiodarone is clearly the antiarrhythmic drug of choice. According to latest data, an early interventional treatment of atrial fibrillation by pulmonary vein ablation may be beneficial and has the potential to reduce mortality in special subgroups of patients. New developments in the field of antidiabetic drugs seem to be promising for reduction of mortality and hospitalization in patients with heart failure.

Purpose Renal function following ventricular assist device (VAD) implantation is a key determinant of survival. The purpose of our study was to investigate whether the development of acute kidney injury (AKI) prior to, or following, VAD implantation influenced survival to transplant. We also sought to determine if the use of extra-corporeal membrane oxygenation (ECMO) or intra-aortic balloon pump (IABP) influenced AKI pre or post-VAD. Methods We undertook a single-centre retrospective cohort study examining outcomes in patients who underwent VAD implantation between 2010 and 2020. AKI was defined as per the KDIGO guidelines. The primary outcome was survival to transplant. Results 61% (96/158) of patients experienced pre-VAD AKI which predicted an increased risk of mortality (OR 2.32, p=0.032, CI 1.07 - 5.04). The incidence of post-VAD AKI was 54% (89/165) which was similarly associated with an increased risk of mortality (OR 2.49, p=0.012, CI 1.21 - 5.13). 67% (64/96) of patients who experienced pre-VAD AKI had post-VAD AKI. Patients who had both pre and post-VAD AKI had a significantly increased mortality prior to transplant with an OR of 3.5 (P=0.01, CI 1.3 - 9.41). Patients with pre-VAD AKI were more likely to require ECMO prior to VAD implantation (OR 2.94) however no difference was observed for IABP use. The use of ECMO or IABP prior to VAD implantation did not influence post-VAD AKI. Conclusion Acute kidney injury both pre and post-VAD implantation reduced likelihood of survival to transplant. Patients with AKI prior to VAD insertion were more likely to require ECMO, however the use of ECMO or IABP pre-VAD insertion did not appear to influence post-VAD AKI.

Introduction Standard guideline-directed neurohumoral blocking therapy is often continued or initiated after left ventricular assist device (LVAD) implantation once haemodynamics are stabilised. Angiotensin/neprilysin inhibitors (ARNI) are well integrated into international guidelines, but the role of these agents in LVAD patients is unclear. In LVAD patients with high afterload sensitivity, small preload changes can lead to suboptimal LV filling and intermittent suction-mediated inflow cannula obstruction. Case Report We investigated the haemodynamic influence of ARNI on LVAD flow, as a surrogate marker of possible suction events, using the accessible logfile data from an in-vivo HeartWare(HW) device, which captures instantaneous power and derived flow every 15-minutes. We extracted the logfile data of a patient who, after stabilisation on ARNI therapy following LVAD implantation, ultimately ceased due to labile arterial pressures. Using the patient as their own control we calculated 1) the mean flow using a running average, 2) the pulsatility index (PI) from minimum/maximum flows, and 3) potential suction events (defined as outlier flow events two standard deviations from the mean). Mean flow was similar off (3.86±0.5l L/min) compared to on (3.78±0.7L/min) ARNI therapy. The PI was numerically higher on therapy (2.1±0.2 L/min) compared to no therapy (1.7±0.3 L/min). There were numerically many more outlier flow events with ARNI therapy (78) compared to no therapy (9), which may correlate with suction events, and suggests haemodynamic instability on therapy. Summary Whilst a few small studies have demonstrated general tolerability of ARNIs in LVAD patients, potent venodilatory and anti-hypertensive effects can cause unfavourable haemodynamics. We show evidence of increased haemodynamic instability evident from controller logfiles possibly due to a disproportionate reduction in preload relative to afterload with increased uncoupling of ventricular to arterial elastance.

Purpose Rejection in heart transplant recipients is often diagnosed by surveillance biopsies as most patients are asymptomatic. Nevertheless, rejection, if left untreated, can produce progressive diastolic dysfunction followed by systolic heart failure. This in turn will cause an increase in central venous pressure due to decreased ventricular compliance. With this in mind we sought out to determine if elevated central venous pressures measured invasively at the time of the biopsy correlated with the presence of rejection. Methods Patients undergoing an endomyocardial biopsy between June and October 2020 were included. The invasive JVP was measured before and after the procedure by measuring the height of the blood column in the side port of the sheath open to the atmospheric pressure. The biopsy results were reported according to the 2004 ISHLT revision. Differences in median JVP for each biopsy result group (0, 1R, 2R, 3R) were compared using a Mann-Whitney test. The histogram density for each biopsy group was graphed using a Kernel density plot. Results Eighty-four patients underwent one or more endomyocardial biopsies, with a total of 374 biopsies performed. Of all procedures, 187 were grade 0 for rejection, 168 were grade 1R and 18 were grade 2R. One patient had Grade 3R rejection (not shown in illustration) The median JVP was not statistically different between the three groups and the numerical difference was not clinically meaningful (figure 1 A). The Kernel density plot (figure 1 B) demonstrates the similarities between the groups. The lack of correlation between invasive JVP and rejection persists if data from the first 2 weeks post heart transplant are excluded. Conclusion In our dataset, there was no clinical or statistical difference in median invasive JVP and rejection grade between the biopsy result groups. One limitation is that we only had one patient with severe rejection (3R). Overall, our findings reinforce the need for surveillance biopsies.

Purpose Worsening renal function (WRF) in patients supported with ventricular assist devices (VAD) is associated with poor outcomes. Postulated mechanisms include right ventricular (RV) dysfunction, low pulsatility from continuous flow, and chronic haemolysis (CH). We aim to determine whether these predict WRF. Methods Consecutive VAD implants between 2010 - 2019 were analysed. Estimated glomerular filtration rate (eGFR - ml/min/m2), lactate dehydrogenase (LDH) and transthoracic echocardiogram (TTE) were collected until death/transplant to 12-months following implant. Demographics and medications 3-months post-implant were recorded. Adverse events included mortality, gastrointestinal (GI) bleed, ischaemic stroke, intracranial haemorrhage, pump thrombosis and driveline infection at any time until death/transplant.WRF was defined as drop in Kidney Disease Improving Global Outcomes Chronic Kidney Disease (KDIGO CKD) stage from baseline to last recorded eGFR. CH defined by elevated LDH. Pulsatility index (PI) derived from mean, peak and trough VAD flows at 1, 3 and 12 months. Results 173 patients included, WRF occurred in 49 patients. WRF was associated with increased GI bleed (odds ratio [OR] 4.41, p=0.02) and ischemic stroke (OR 5.05, p=0.018). WRF occurred less frequently in those on beta-blockers (OR 0.31, p = 0.009) and renin-angiotensin-system inhibitors (OR 0.31, p = 0.009). Although not statistically significant, those with WRF had median higher baseline eGFR (WRF vs. no WRF 68 vs 55, p=0.598). Less profound eGFR improvement at 1 month was seen in patients with WRF (1 vs. 25.5, p = 0.021), resulting in numerically lower eGFR at 1-month in those with WRF (77 vs. 83, p=0.119) respectively. WRF was not predicted by PI, CH or change in RV function on TTE. Conclusion WRF is associated with increased morbidity in patients supported with VAD, although the mechanism for this is unclear. Further studies are required to define CH and low pulsatility to determine their impact on WRF.

Purpose Most heart failure patients undergoing ventricular assist device (VAD) implantation are managed with guideline-based therapy including the implantation of defibrillation capable device (ICD). Prior to surgery, programming allowing therapy with lower threshold could be lifesaving. After surgery, the defibrillator should be reprogrammed to protect the patient against painful, unnecessary shocks, as the circulation will be supported even in ventricular fibrillation. Difficulties in interrogation of ICD in patients with both HeartMate-II and HeartMate3 devices have been previously reported, related to the VAD-produced electromagnetic interference. Most cases result in a problem of communication between the ICD and the corresponding interrogating console. Methods An electronic search was performed to identify all articles and abstracts published on the topic until July 2019. To the list, we added one case from our clinical experience as well as manufacturer described cases of incompatibility. Results We identified 473 publications. Fourteen publications were ultimately included. Those publications described 22 patients with device interrogation issues post VAD implantation. To regain control of the device complete replacement of the ICD/CRT/PM was performed in 10 patients, and in one the implantation side was changed. In 11 cases a shielding technique was successfully utilized. From the data, we can extract the names of 14 devices with a documented communication problem. There were no reported cases of adverse interaction between HeartWare and ICDs. Conclusion Given the reported VAD-associated EMI interaction with ICD interrogation due to interruption of the handshake-signal to initiate ICD interrogation, it is likely all the variants of one specific ICD (1 lead, 2 lead, CRT) will also suffer from the same problem. More ex-vivo research is needed to better understand the phenomenon, and clinicians and patients with the listed ICDs need to be aware of the potential loss of ICD control with HM2 or HM3.

Purpose HeartWare assist device (HVAD) monitor provides flow and power waveform information which has been shown to respond to changes in physiological loading conditions, cardiac contractility and aortic valve status. Instantaneous point data is recorded every 15 minutes into the controller logfile. Because some phenomena are of short duration or need an immediate intervention (such as suction or tamponade), significant changes may not be captured within the logfile. We present a simple method to capture the displayed waveforms via a smartphone photo followed by re-digitization for data extraction. Waveform recording provides an opportunity for teaching or research. Methods During an interesting event, a photo of the screen of the HVAD monitor is taken. The photographer will take care to capture the border of the waveform screen as reference. The second step is the restitution of parallel lines using the smartphone application TurboScan (picksoft, V.3.0.2). This will use the border of the screen to straighten the whole picture. Loss of quality can happen during this stage if an extreme angle is used. To reconstruct the axis, we feed the picture in WebPlotDigitalizer (Atomeris, V.4.2). Using the built-in VAD-screen scale, the software will output a table of calibrated values corresponding to the flow or power trace. Results Using an R-script (3.6.1) written within R-studio (V.12.1355), we can reproduce flow and power waveforms identical to that displayed from the HVAD controller with sampling frequency of data up to 100Hz. This can be used as an algorithm input for further waveform analysis (waveform, rhythm, PI) or for illustration purposes. Our illustrative case shows a photo taken during a normal VAD-clinic appointment and reconstituted using our technique. Conclusion This technique is cheap, easy to use at the bedside or clinic and represents an opportunity to capture interesting waveform events for teaching or illustration purposes or subsequent algorithm development.

Purpose Pump thrombosis (PT) remains a serious complication in patients supported with a ventricular assist device (VAD). In our institution, HeartWare HVAD patients with PT are thrombolysed with systemic Alteplase infusion until restoration of normal power consumption or maximum infusion duration of 20 hours. Although most PT events resolve with single thrombolysis, PT can re-occur requiring further thrombolysis and/or pump exchange. In this prospective exploratory observational study, we opened and inspected all explanted pumps that required thrombolysis for PT. Methods VADs were retrieved post-heart transplantation and opened for inspection. All impeller (rotor) surfaces, and internal upper and lower pump housing surfaces were inspected and photographed. Results From August 2017 through September 2019, 7 patients (mean age 54±7.6 years, 57% male) were thrombolysed for PT with a median duration of support to first thrombolysis of 307 days (range, 99 to 852 days). Five patients were thrombolysed once, 1 twice and 1 three times. Clinical parameters and pump power consumption returned to normal for each thrombolysis event for all patients. Inspection of the pump at explant was normal in all cases, except for the patient thrombolysed multiple times. In that patient (thrombolysed on days 99, 154, 204), the lower surface of the impeller was worn on one edge, suggesting impeller imbalance with corresponding marking on the ceramic housing surface. (Image) Conclusion Patients with recurrent PT episodes requiring thrombolysis may have changes in pump surface not previously reported. Pump replacement may be warranted in these cases. Whether this is due to impeller instability or other factors is unknown. Routine inspection of explanted pumps may provide insights into thrombosis mechanisms.

Pharmacological therapy of heart failure with reduced ejection fraction Abstract. Pharmacological therapy for heart failure has made great progress over the last three decades and evidence-based therapies have significantly improved survival and quality of life. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers are the cornerstone of the heart failure therapy; indicated in virtually every patient with heart failure and reduced ejection fraction. As soon as the left ventricular ejection fraction decreases below 35 % and / or symptoms are still present (NYHA II-IV), a mineralocorticoid receptor antagonist should be added. A rather recent addition to current heart failure therapy with convincing data is the substance combination sacubitril / valsartan. It is indicated for patients with persistent symptomatic heart failure despite optimal medical therapy with ACE inhibitors or ARBs, beta-blockers, and MRAs. Crucial for all mentioned substances is to aim for the maximal tolerated dose. Various additional therapies have no proven survival benefit but are important for symptom control in everyday life. Above all the diuretics, where loop diuretics show a better effect profile compared to thiazide diuretics. Furthermore, achieving an optimal iron status (the limit to start a substitution is significantly higher than in patients without heart failure), decreasing the heart frequency with Ivabradine (if heart rate persists above 70 / min despite fully dosed betablocker) and «lifestyle changes» can add to the success of the medical treatment. The importance of digoxin has been steadily decreasing. The previously advocated therapeutic anticoagulation in patients with severely reduced LVEF is not propagated anymore. Significant arrhythmias (especially atrial fibrillation and ventricular arrhythmias) are common in advanced diseases. In addition to beta-blockers, amiodarone is clearly the antiarrhythmic drug of choice. According to latest data, an early interventional treatment of atrial fibrillation by pulmonary vein ablation may be beneficial and has the potential to reduce mortality in special subgroups of patients. New developments in the field of antidiabetic drugs seem to be promising for reduction of mortality and hospitalization in patients with heart failure.Zusammenfassung. Die medikamentöse Therapie der Herzinsuffizienz (HI) hat im Verlauf der letzten drei Dekaden grosse Fortschritte gemacht. Evidenz-basierte medikamentöse Therapien haben Überleben und Lebensqualität entscheidend verbessert. Die medikamentöse Stufentherapie der Herzinsuffizienz beginnt mit den Angiotensin-konvertierenden-Enzym Hemmern (ACEH) oder Angiotensin-Rezeptorblockern (ARB) und Betablockern, welche bei praktisch jedem Patienten mit einer Herzinsuffizienz und reduzierter Ejektionsfraktion indiziert sind. Fällt die linksventrikuläre Ejektionsfraktion unter 35 % und / oder persistieren die Symptome (NYHA II-IV) kommt zusätzlich ein Mineralokortikoidrezeptor-Antagonist (MRA) zum Einsatz. Relativ neu, aber mit überzeugenden Daten, ist die Substanzkombination Sacubitril / Valsartan. Das Erreichen der maximal verträglichen Dosis der einzelnen Medikamente ist essentiell für den Therapieerfolg. Diverse Zusatztherapien haben keinen erwiesenen Einfluss auf das Überleben, sind jedoch oft wesentlich für die Symptomfreiheit im Alltag. Wichtige Vertreter hierfür sind die Diuretika (Schleifendiuretika zeigen ein besseres Wirkungsprofil und sind den Thiaziden vorzuziehen), die Therapie eines Eisenmangels oder der Einsatz des Frequenzmodulators Ivabradin. Digoxin hat aktuell nur noch einen sehr begrenzten Stellenwert. Signifikante Rhythmusstörungen (vor allem Vorhofflimmern und ventrikuläre Arrhythmien) gehören zum klassischen Krankheitsverlauf. Neben Betablockern ist Amiodaron das Antiarrhythmikum der Wahl. Mit der frühen interventionellen Behandlung des Vorhofflimmerns mittels Pulmonalvenenablation ist gemäss neuster Daten eine Reduktion der Mortalität potentiell möglich. Neue Entwicklungen im Bereich der Antidiabetika sind bezüglich Therapieoptimierungen vielversprechend.

IntroductionThe concept of response time with minimal interval is intimately related to the practice of emergency medicine. The factors influencing this time interval are poorly understood.ProblemIn a process of improvement of response time, the impact of the patient’s age on ambulance departure intervals was investigated.MethodThis was a 3-year observational study. Departure intervals of ambulances, according to age of patients, were analyzed and a multivariate analysis, according to time of day and suspected medical problem, was performed.ResultsA total of 44,113 missions were included, 2,417 (5.5%) in the pediatric group. Mean departure delay for the adult group was 152.9 seconds, whereas it was 149.3 seconds for the pediatric group (P=.018).ConclusionA statistically significant departure interval difference between missions for children and adults was found. The difference, however, probably was not significant from a clinical point of view (four seconds).SchneggB,PasquierM,CarronPN,YersinB,DamiF.Prehospital Emergency Medical Services departure interval: does patient age matter?Prehosp Disaster Med.2016;31(6):608–613.