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Background: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown. Methods: Left atrial (LA) fibrosis was analyzed in samples from patients with AF and concomitant CKD (estimated glomerular filtration rate [eGFR], 2 ) using picrosirius red and compared with AF patients without CKD and patients with sinus rhythm with and without CKD. In a translational approach, male Sprague Dawley rats were fed with 0.25% adenine (AD)-containing chow for 16 weeks to induce CKD. At week 5, AD-fed rats underwent RDN or sham operation (AD). Rats on normal chow served as control. After 16 weeks, cardiac function and AF susceptibility were assessed by echocardiography, radiotelemetry, electrophysiological mapping, and burst stimulation, respectively. LA tissue was histologically analyzed for sympathetic innervation using tyrosine hydroxylase staining, and LA fibrosis was determined using picrosirius red. Results: Sirius red staining demonstrated significantly increased LA fibrosis in patients with AF+CKD compared with AF without CKD or sinus rhythm. In rats, AD demonstrated LA structural changes with enhanced sympathetic innervation compared with control. In AD, LA enlargement was associated with prolonged duration of induced AF episodes, impaired LA conduction latency, and increased absolute conduction inhomogeneity. RDN treatment improved LA remodeling and reduced LA diameter compared with sham-operated AD. Furthermore, RDN decreased AF susceptibility and ameliorated LA conduction latency and absolute conduction inhomogeneity, independent of blood pressure reduction and renal function. Conclusions: In an experimental rat model of CKD, RDN inhibited progression of atrial structural and electrophysiological remodeling. Therefore, RDN represents a potential therapeutic tool to reduce the risk of AF in CKD, independent of changes in renal function and blood pressure.

Aims: Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). Methods and results: The MEMS-HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS-HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2] vs. non-users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2, P = 0.0002, P Conclusions: In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes.

In heart failure (HF), acute decompensation can occur quickly and unexpectedly because of worsening of chronic HF or to new‐onset HF diagnosed for the first time (‘de novo’). Patients presenting with acute HF (AHF) have a poor prognosis comparable with those with acute myocardial infarction, and any delay of treatment initiation is associated with worse outcomes. Recent HF guidelines and recommendations have highlighted the importance of a timely diagnosis and immediate treatment for patients presenting with AHF to decrease disease progression and improve prognosis. However, based on the available data, there is still uncertainty regarding the optimal ‘time‐to‐treatment’ effect in AHF. Furthermore, the immediate post‐worsening HF period plays an important role in clinical outcomes in HF patients after hospitalization and is known as the ‘vulnerable phase’ characterized by high risk of readmission and early death. Early and intensive treatment for HF patients in the ‘vulnerable phase’ might be associated with lower rates of early readmission and mortality. Additionally, in the chronic stable HF outpatient, treatments are often delayed or not initiated when symptoms are stable, ignoring the risk for adverse outcomes such as sudden death. Consequently, there is a dire need to better identify HF patients during hospitalization and after discharge and treating them adequately to improve their prognosis. HF is an urgent clinical scenario along all its stages and disease conditions. Therefore, time plays a significant role throughout the entire patient's journey. Therapy should be optimized as soon as possible, because this is beneficial regardless of severity or duration of HF. Time lavished before treatment initiation is recognized as important modifiable risk factor in HF.

Medications with proven benefit in patients with heart failure with reduced ejection fraction are recommended, according to prospective large clinical trials, in the stable patient after careful up-titration in a strict sequential order. Although the relevance of careful clinical up-titration is unproven, there is evidence that after recompensation and shortly after hospital discharge, the rate of cardiovascular death and hospitalization is high. Clinical studies provided evidence that the onset of treatment effects is rapid, occurring within 28 days with most of these drugs used, and in some trials, early treatment after discharge or already started in the hospital has provided benefits. Therefore, early treatment without deferring it to the stable outpatient may be useful to reduce cardiac-related events further. This expert opinion proposes treatment layering according to individual patient phenotypes involving heart rate, blood pressure, impaired renal function, and electrolyte disturbances, as well as dedicated subgroups of patients with specific requirements for treatment initiation. This complements other approaches that suggest starting sequential treatment according to the size of treatment effects of drugs, specific cardiac diseases, and patient wishes. Patient phenotyping may guide personalized drug layering in heart failure with reduced ejection fraction that provides the best outcomes, whereas pragmatic clinical trials are warranted to scrutinize the effectiveness of these approaches.

Die chronische Niereninsuffizienz (CKD) und der Diabetes mellitus (DM) sind haufige Komorbiditaten kardialer Erkrankungen. Die leitliniengerechte Therapie der CKD und des DM tragt daher entscheidend zur Morbiditats- und Mortalitatsreduktion kardiologischer Patienten bei. Dieser Jahresruckblick fasst die wichtigsten Aspekte zur Behandlung des DM und der CKD aus Sicht des Kardiologen zusammen. Zunachst werden Masnahmen zur Einschatzung des kardiovaskularen Risikos und zur Pravention einer CKD bei Patienten mit DM vorgestellt. Daruber hinaus wird ausfuhrlich auf die Bedeutung der Natrium-Glukose Kotransporter-2-Inhibitoren sowie der GLP(„glucagon-like peptide“)-1-Rezeptorantagonisten zur Therapie des DM und der CKD eingegangen. Auserdem wird die Effektivitat der renalen Denervation bei DM und CKD diskutiert.

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF.

BACKGROUND Pulmonary vein isolation (PVI) is a component of standard care for patients with symptomatic atrial fibrillation (AF). Procedural inducibility of AF following PVI has been suggested as predictor of AF recurrence but is discussed controversially. This meta-analysis aimed at evaluating the relevance of electrophysiological inducibility of AF following PVI for future AF recurrences. METHODS A literature search of MEDLINE and Web of Science was performed until April 2020. Prospective trials of PVI in patients with AF and post-procedural atrial stimulation to test for inducibility of AF as well as adequate follow-up for AF recurrence (defined as AF >10 s to >10 min at follow-up) were included. Odds ratios (ORs) were analyzed using random-effects models. RESULTS A total of 11 trials with 1544 patients (follow-up 7-39 months, age 56 ± 6 years, predominantly male 74 ± 6%) were included. Inducibility of AF post-PVI was predictive for AF recurrence during follow-up (OR 2.08; 95% CI 1.25 to 3.46). Prediction for AF recurrence at follow-up was better for patients with paroxysmal AF (OR 4.06; 95% CI 1.39 to 11.91), stimulation in the CS (OR 2.82, 95% CI 1.17 to 6.79). A trend towards higher ORs was seen without the use of isoproterenol (OR 2.43; 95% CI 1.17 to 5.07), as well as few stimulations during induction and a short definition of AF in meta-regression analyses. CONCLUSIONS Electrophysiological inducibility of AF following PVI was predictive for future recurrence of AF, in particular in patients with paroxysmal AF, stimulation in only CS and no use of isoproterenol.

ZusammenfassungInzidenz und Prävalenz der Herzinsuffizienz steigen weltweit. Trotz zahlreicher wissenschaftlicher und klinischer Innovationen ist sie weiterhin mit einer hohen Morbidität und Mortalität behaftet, sodass eine leitliniengerechte Diagnostik und Therapie von entscheidender Bedeutung sind. Die kardiale Dekompensation zählt zu den häufigsten Aufnahmegründen in deutschen Krankenhäusern. Somit stellt die Behandlung herzinsuffizienter Patienten eine erhebliche Herausforderung für das deutsche Gesundheitssystem dar. Dieser Artikel fasst die neuesten wissenschaftlichen Erkenntnisse zur akuten und chronischen Herzinsuffizienz der Jahre 2018 bis 2020 zusammen.

Medications with proven benefit in patients with heart failure with reduced ejection fraction are recommended, according to prospective large clinical trials, in the stable patient after careful up-titration in a strict sequential order. Although the relevance of careful clinical up-titration is unproven, there is evidence that after recompensation and shortly after hospital discharge, the rate of cardiovascular death and hospitalization is high. Clinical studies provided evidence that the onset of treatment effects is rapid, occurring within 28 days with most of these drugs used, and in some trials, early treatment after discharge or already started in the hospital has provided benefits. Therefore, early treatment without deferring it to the stable outpatient may be useful to reduce cardiac-related events further. This expert opinion proposes treatment layering according to individual patient phenotypes involving heart rate, blood pressure, impaired renal function, and electrolyte disturbances, as well as dedicated subgroups of patients with specific requirements for treatment initiation. This complements other approaches that suggest starting sequential treatment according to the size of treatment effects of drugs, specific cardiac diseases, and patient wishes. Patient phenotyping may guide personalized drug layering in heart failure with reduced ejection fraction that provides the best outcomes, whereas pragmatic clinical trials are warranted to scrutinize the effectiveness of these approaches.

Clinical research in cardiology 110(8), 1150-1158 (2021). doi:10.1007/s00392-021-01867-2, Published by Springer, Berlin

Background: Impedance-based remote monitoring (RM) failed to reduce clinical events in the OptiLink heart failure (HF) trial. However, rates of alert-driven interventions triggered by intrathoracic fluid index threshold crossings (FTC) were low indicating physicians’ inappropriate reactions to alerts. Methods: We separated appropriate from inappropriate contacts to FTC transmissions in the OptiLink HF trial (Optimization of Heart Failure Management Using OptiVol™ Fluid Status Monitoring and CareLink™). Appropriate contacts had to meet the following criteria: (1) initial telephone contact within 2 working days after FTC transmission, (2) follow-up contacts according to study protocol, and (3) medical intervention initiated after FTC due to cardiac decompensation. We compared time to cardiovascular death or HF hospitalization between RM patients contacted appropriately or inappropriately and patients with usual care. Results: In the RM group, at least one FTC alert was transmitted in 356 patients (70.5%; n=505). Of note, only 55.5% (n=758) of all transmitted FTCs (n=1365) were followed by an appropriate contact. While 113 patients (31.7%; n=356) have been contacted appropriately after every FTC, in 243 patients (68.3%; n=356) at least one FTC was not responded by an appropriate contact. Compared with usual care, RM with appropriate contacts to FTC alerts independently reduced the risk of the primary end point (hazard ratio, 0.61 [95% CI, 0.39–0.95]; P =0.027). Conclusions: RM appropriate reactions to FTC alerts are associated with significantly improved clinical outcomes in patients with advanced HF and implantable cardioverter-defibrillators.

Aims To investigate the effects of adequate reactions to telemedicine alerts triggered by fluid index threshold crossings (FTC) on clinical outcomes in the OptiLink HF trial. Methods We separated adequate from inadequate reactions to FTC transmissions in patients with remote impedance-based monitoring (RM) of fluid status in the OptiLink HF trial. Adequate contacts had to meet the following criteria: i) initial telephone contact within 2 working days after FTC transmission, ii) follow-up contacts according to study protocol, and iii) medical intervention initiated after FTC due to true fluid overload. We compared time to cardiovascular (CV) death or heart failure (HF) hospitalization and all CV- and HF-hospitalizations at follow-up between RM patients contacted adequately or inadequately and patients with usual care (UC). Results In the RM group, transmission of at least one FTC alert occurred in 356 patients (70.5%; n=505). While 113 patients (31.7%; n=356) have been contacted adequately after every FTC, in 243 patients (68.3%; n=356) at least one FTC was not responded by an adequate contact. Adequate responses to RM significantly reduced risk of the primary endpoint (hazard ratio (HR), 0.68; 95% confidence interval (CI) 0.48–0.95; p=0.025, figure 1), and led to a significantly lower number of CV (52.1±7.5 vs. 99.9±19.8; p=0.007) and HF hospitalizations per 100 patient years when compared with UC (26.1±4.4 vs. 67±15.2; p=0.007). Conclusion RM with adequate reactions to FTC alerts significantly reduced total number of both CV and HF hospitalizations and improved clinical outcomes in patients with advanced HF and implantable cardioverter defibrillator (ICD). Funding Acknowledgement Type of funding source: None

Background Remote monitoring of patients suffering from heart failure (HF) did not result in improved clinical outcomes in the OptiLink-HF trial. However, initiation of medical intervention after transmission of telemedicine alerts triggered by fluid index threshold crossings (FTCs) was low. The relation between weekday of transmission of FTC and subsequent patient contact is unknown. Methods Patients enrolled in the intervention arm of the OptiLink HF trial (n=505, age 66.1±10.1, male 77.2, EF 26.7±6.1%) were analyzed according to the weekday of transmission of FTC. Transmissions of FTC on Mondays to Thursdays were categorized as TD1, Fridays to Sundays as well as bank holidays as TD2. Primary endpoint was time between transmission and telephone contact; secondary endpoints were subsequent medical intervention and hospitalizations. Results During a follow-up of 18 months, 1364 FTC (866 (63.5%) categorized to TD1, 498 (36.5%) to TD2) alerts occurred in 356 patients. In 46.2% of FTC same day telephone contact was performed in group TD1 compared to 18.3% in group TD2 (p Conclusion Transmission of FTC alerts during weekends and on bank holidays were less likely associated with timely patient contacts and initiation of pharmacological intervention than during the week. Telemedical centers providing 24/7 remote monitoring service might help to optimize patient care. Funding Acknowledgement Type of funding source: None

The incidence and prevalence of heart failure are increasing worldwide. Despite numerous scientific and clinical innovations the mortality and morbidity rates in heart failure patients remain high, so that guideline-conform diagnostics and treatment are of decisive importance. Cardiac decompensation is one of the leading reasons for hospital admissions in Germany. Thus, the treatment of patients with heart failure represents a substantial challenge for the German healthcare system. This article highlights the latest scientific knowledge on acute and chronic heart failure from the years 2018-2020.Inzidenz und Prävalenz der Herzinsuffizienz steigen weltweit. Trotz zahlreicher wissenschaftlicher und klinischer Innovationen ist sie weiterhin mit einer hohen Morbidität und Mortalität behaftet, sodass eine leitliniengerechte Diagnostik und Therapie von entscheidender Bedeutung sind. Die kardiale Dekompensation zählt zu den häufigsten Aufnahmegründen in deutschen Krankenhäusern. Somit stellt die Behandlung herzinsuffizienter Patienten eine erhebliche Herausforderung für das deutsche Gesundheitssystem dar. Dieser Artikel fasst die neuesten wissenschaftlichen Erkenntnisse zur akuten und chronischen Herzinsuffizienz der Jahre 2018 bis 2020 zusammen.

(1) Background: Atrial fibrillation (AF) is associated with anxiety, depression, and chronic stress, and vice versa. The purpose of this study was to evaluate potential effects of pulmonary vein isolation (PVI) on psychological factors. (2) Methods: Psychological assessment was performed before PVI as well as after six months. (3) Results: A total of 118 patients [age 64 ± 9 years, 69% male, left ventricular ejection fraction 57 ± 8%, 56% paroxysmal AF] undergoing PVI were included. After PVI, significant improvements were observed in the mean total heart-focused anxiety (HFA) score, as well as in the Cardiac Anxiety Questionnaire (CAQ) sub-scores: HFA attention, HFA fear, and HFA avoidance scores. Subgroup analyses showed an association of improvement with freedom of documented AF recurrence. Mean scores of general anxiety and depression evaluated by the Hospital Anxiety and Depression Scale (HADS) decreased significantly after PVI in all subgroups regardless of AF recurrence. Further, both physical and mental composite scores of the Short Form Health Survey (SF-12) increased significantly from baseline. (4) Conclusions: PVI results in a significant reduction in HFA. Improvements in general anxiety and depressive symptoms did not seem to be related only to rhythm control per se. Therefore, CAQ may represent a more specific evaluation tool as HADS in patients with AF.

Heart failure (HF) treatment should be optimized in addition to guideline-directed and recommended drugs to achieve an appropriate heart rate (i.e. 50-60 bpm) by ivabradine in patients with a heart rate70 bpm in sinus rhythm and with an ejection fraction ≤35%. Heart rate reduction was to reduce cardiovascular death and HF hospitalization dependent on baseline resting heart rate. In particular in patients at a heart rate75 bpm, a reduction in cardiovascular death, all-cause death, HF death, HF hospitalization and all-cause hospitalization has been observed. The optimal heart rate achieved appears to be between 50-60 bpm, if well tolerated as in these patients the lowest event rate is observed on treatment. Heart rate reduction is, therefore, a treatable risk factor in chronic HF. Observational studies support the concept that it is a risk indicator in other cardiovascular and non-cardiovascular conditions. Whether heart rate reduction is also modifying risk in other conditions than chronic HF should be explored in prospective clinical trials.