Digital Technologies to Support Better Outcome and Experience of Care in Patients with Heart Failure.

PURPOSE OF REVIEW: In this article, we review a range of digital technologies for possible application in heart failure patients, with a focus on lessons learned. We also discuss a future model of heart failure management, as digital technologies continue to become part of standard care. RECENT FINDINGS: Digital technologies are increasingly used by healthcare professionals and those living with heart failure to support more personalised and timely shared decision-making, earlier identification of problems, and an improved experience of care. The COVID-19 pandemic has accelerated the acceptability and implementation of a range of digital technologies, including remote monitoring and health tracking, mobile health (wearable technology and smartphone-based applications), and the use of machine learning to augment data interpretation and decision-making. Much has been learned over recent decades on the challenges and opportunities of technology development, including how best to evaluate the impact of digital health interventions on health and healthcare, the human factors involved in implementation and how best to integrate dataflows into the clinical pathway. Supporting patients with heart failure as well as healthcare professionals (both with a broad range of health and digital literacy skills) is crucial to success. Access to digital technologies and the internet remains a challenge for some patients. The aim should be to identify the right technology for the right patient at the right time, in a process of co-design and co-implementation with patients.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

[Telemonitoring and pulmonary artery pressure-guided treatment of heart failure]. / Telemonitoring und Pulmonalisdruck-geführte Therapie der Herzinsuffizienz.

Heart failure (HF) is an emerging epidemic associated with significant morbidity and mortality, impaired quality of life and high healthcare costs. Despite major advances in pharmacological and device-based therapies, mortality and morbidity have remained high after an index hospitalization for acute cardiac decompensation (ACD). Randomized trials evaluating various forms of noninvasive telemonitoring failed to improve rehospitalization rates in such patients, possibly due to lack of sensitivity of clinical signs and symptoms as early indicators of HF. Among different implantable monitoring devices, wireless remote monitoring of the pulmonary artery pressure (PAP) with the CardioMEMS™ sensor (Abbott, Sylmar, CA, USA) has been shown to be safe and clinically effective in the USA. The patients showed substantial reductions in hospital admissions for ACD, irrespective of left ventricular pump function, because PAP-guided HF management facilitates timely recognition of incipient ACD and appropriate modification of medical treatment before hospitalization becomes unavoidable. These encouraging results have also stimulated evaluation of this novel technology outside the USA. Studies are also underway in Europe and European HF guidelines recommend considering implantation of a CardioMEMS™ sensor in high-risk patients (class IIb-B). More technologically refined implantable hemodynamic monitoring systems allowing, for example, left atrial pressure measurements, are under development. Promising novel approaches to using information from such devices include continuous hemodynamic monitoring and patient self-management based on the pressure information. Thus, pressure-guided HF management is likely to further expand in the future and may help improve clinical outcomes also in high-risk HF populations.

CRP genetic variants are associated with mortality and depressive symptoms in chronic heart failure patients.

OBJECTIVE: Heart failure (HF) is a complex medical condition with a multitude of genetic and other factors being involved in the pathogenesis. Emerging evidence points to an involvement of inflammatory mechanisms at least in subgroups of patients. The same is true for depression and depressive symptoms, which have a high prevalence in HF patients and are risk factors for the development and outcomes of cardiovascular disease. METHODS: In 936 patients of the Interdisciplinary Network Heart Failure (INH) program, CRP and IL-6 protein blood levels were measured and genetic variants (single nucleotide polymorphisms) of the CRP and IL6 gene analyzed regarding their influence on mortality. RESULTS: Less common recessive genotypes of two single nucleotide polymorphisms in the CRP gene (rs1800947 and rs11265263) were associated with significantly higher mortality risk (p < 0.006), higher CRP levels (p = 0.029, p = 0.006) and increased depressive symptoms in the PHQ-9 (p = 0.005, p = 0.003). Variants in the IL-6 gene were not associated with mortality. CONCLUSION: Our results hint towards an association of less common CRP genetic variants with increased mortality risk, depressive symptoms and peripheral CRP levels in this population of HF patients thereby suggesting a possible role of the inflammatory system as link between poor prognosis in HF and depressive symptoms.

Simple screening tools predict death and cardiovascular events in patients with rheumatic disease.

OBJECTIVES: Patients with rheumatic disease (RD) have an increased mortality risk compared with the general population, mainly due to cardiovascular disease (CVD). We aimed to identify patients at high risk of CVD and mortality by comparing three screening tools suitable for clinical practice. METHOD: In this prospective, single-centre study, consecutive patients with rheumatoid arthritis (RA), systemic autoimmune disease (SAI), or spondyloarthritides (SpA) including psoriatic arthritis underwent a comprehensive cardiovascular risk assessment. Patients were predefined as being at high risk for cardiovascular events or death if any of the following were present: European Systematic COronary Risk Evaluation (SCORE) ≥ 3%, N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥ 200 pg/mL, or any pathological electrocardiogram pattern. RESULTS: The patient population (n = 764) comprised 352 patients with RA, 260 with SAI, and 152 with SpA. After a median follow-up of 5.2 years, 6.0% of RD patients had died (7.0%, 7.2%, and 1.4% of patients in the RA, SAI, and SpA subgroups), and 5.0% had experienced a cardiovascular event (5.0%, 6.4%, and 2.8%, respectively). For all RD patients and the RA and SAI subgroups, NT-proBNP ≥ 200 pg/mL and SCORE ≥ 3% identified patients with a 3.5-5-fold increased risk of all-cause death and cardiovascular events. Electrocardiogram pathology was associated with increased mortality risk, but not with cardiovascular events. CONCLUSION: NT-proBNP ≥ 200 pg/mL or SCORE ≥ 3% identifies RA and SAI patients with increased risk of cardiovascular events and death. Both tools are suitable as easy screening tools in daily practice to identify patients at risk for further diagnostics and closer long-term follow-up.

[Cardiac remodeling after myocardial infarction : Clinical practice update]. / Kardiales Remodelling nach Myokardinfarkt : Update für die klinische Praxis.

Heart failure remains a frequent cause of death and is the leading reason for hospitalization in Germany although therapeutic options have significantly increased over the past years particularly in heart failure with reduced ejection fraction. Clinical symptoms are usually preceded by cardiac remodeling, which was originally defined only by left ventricular dilatation and depressed function but is also associated with typical cellular and molecular processes. Healing after acute myocardial infarction is characterized by inflammation, cellular migration and scar formation. Cardiac remodeling is accompanied by adaptive changes of the peripheral cardiovascular system. Since prevention is the primary goal, rapid diagnosis and treatment of myocardial infarction are mandatory. Early reperfusion therapy limits infarct size and enables the best possible preservation of left ventricular function. Standard pharmacotherapy includes angiotensin-converting enzyme inhibitors, angiotensin-1-receptor blockers and beta blockers. In addition, mineralocorticoid receptor antagonists have proven beneficial. Compounds specifically targeting infarct healing processes are currently under development.

[Depression and heart failure - a twofold hazard? : Diagnosis, prognostic relevance and treatment of an underestimated comorbidity]. / Depression und Herzinsuffizienz ­ doppeltes Risiko? : Diagnostik, prognostische Bedeutung und Therapie einer unterschätzten Komorbidität.

Heart failure and depression are widespread diseases and of particular clinical and economic relevance. Compared with the general population depression is up to 5­times more common in patients with heart failure, with adverse effects on morbidity, mortality, quality of life and treatment costs. Depressive symptoms overlap with those of heart failure which renders diagnosis difficult. Simple screening tools, e. g. the two-item patient health questionnaire, help to recognize depression in the clinical routine. To date, there is no evidence that antidepressant pharmacotherapy improves mood and clinical outcomes in patients with heart failure and comorbid depression and antidepressant pharmacotherapy remains to be decided on a case by case basis; however, physical training, cognitive behavioral therapy and multidisciplinary comprehensive disease management improved symptoms and/or prognosis in a limited number of randomized studies.

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.

[Holistic therapy of chronic heart failure]. / Ganzheitliche Behandlung der chronischen Herzinsuffizienz.

The rising prevalence and increasing disease-related costs render chronic heart failure a rapidly growing socioeconomic challenge. The concerted action of guideline-adjusted therapy and holistic patient care is essential to achieve improvements in mortality, morbidity, functional status and quality of life of patients with symptomatic heart failure. Holistic care strategies comprise consideration of comorbidities and individual needs, lifestyle recommendations and multidisciplinary management programs for high-risk symptomatic patients in addition to basic medication and surgical therapies. For optimal patient care and coaching, seamless interaction is required between in-hospital treatment and outpatient facilities. Moreover, the palliative needs of heart failure patients need to be considered, a topic that is currently not receiving enough attention.

Comorbid depression in heart failure.

Heart failure (HF) is highly prevalent and associated with adverse outcomes and high costs. Compared with the general population, depression is up to five times more common in HF patients. Comorbid depression increases morbidity and mortality risk and health-care expenditures even further and decreases quality of life. Possible, often interrelated, mediators of these effects include biological, behavioral, and psychosocial factors. Screening instruments such as the self-administered PHQ-2 facilitate detection of patients at risk. Although antidepressants may improve psychological well-being, no positive effects on hard clinical endpoints have been demonstrated to date.

Complement C3c as a biomarker in heart failure.

INTRODUCTION: Experimental data indicates an important role of the innate immune system in cardiac remodeling and heart failure (HF). Complement is a central effector pathway of the innate immune system. Animals lacking parts of the complement system are protected from adverse remodeling. Based on these data, we hypothesized that peripheral complement levels could be a good marker for adverse remodeling and prognosis in patients with HF. METHODS AND RESULTS: Since complement activation converges on the complement factor C3, we measured serum C3c, a stable C3-conversion product, in 197 patients with stable systolic HF. Subgroups with normal and elevated C3c levels were compared. C3c levels were elevated in 17% of the cohort. Patients with elevated C3c levels exhibited a trend to better survival, slightly higher LVEF, and lower NTpro-BNP values in comparison to patients with normal C3c values. No differences were found regarding NYHA functional class. Significantly more patients with elevated C3c had preexisting diabetes. The prevalence of CAD, arterial hypertension, and atrial fibrillation was not increased in patients with elevated C3c. CONCLUSION: Elevated C3c levels are associated with less adverse remodeling and improved survival in patients with stable systolic heart failure.

Peripartum cardiomyopathy. An update.

Peripartum cardiomyopathy (PPCM) is a rare disease of the heart muscle that affects women with previously unknown heart diseases during pregnancy or in the first months after delivery. Cardinal symptoms are dyspnoea and fluid retention. However, tachycardia, cardiogenic thromboembolism and other clinical signs of cardiac dysfunction may also herald this uncommon cause of heart failure. The estimated incidence of PPCM shows large regional variations: in Europe and the United States it is between 1:2000 and 1:4000. The markedly higher incidence rates observed in Haitian or South African women (up to 1:300) suggest that genetic or environmental factors may play a pathogenetic role. However, the underlying aetiology of PPCM still is unclear. Besides genetic susceptibility an abnormal autoimmune response against cardiac tissue components, viral infections or an irregular activity of cathepsin D generating a potentially cardio-toxic splice variant of prolactin have been discussed. New therapeutic strategies as immune modulation or prolactin inhibition were therefore suggested, but are not yet established. Treatment strategies focus on the standard therapies for heart failure and its complications. During pregnancy heart failure therapy is limited to substances without fetotoxic effects. But even with optimal heart failure therapy the course of the disease exhibits large variations ranging from full recovery to deterioration of heart function and even early cardiac death. This review cumulates the current knowledge on PPCM and aims to raise awareness for this rare and potentially life-threatening disorder amongst all medical professionals involved in the care for pregnant women.

Implementation of pharmacotherapy guidelines in heart failure: experience from the German Competence Network Heart Failure.

AIM: To evaluate the implementation of current pharmacotherapy guidelines of heart failure and to identify factors associated with high pharmacotherapy guideline adherence in heart failure patients. METHODS AND RESULTS: We pooled data from seven studies performed in the context of the German Competence Network Heart Failure selecting patients with chronic systolic heart failure and left ventricular ejection fraction (LVEF) <45% (n = 2,682). The quality of pharmacotherapy was evaluated by calculating the guideline adherence indicator (GAI), which considers three (GAI-3) or five (GAI-5) of the recommended heart failure substance classes and accounts for respective contraindications. GAI-3 was categorized as perfect (GAI = 100%: 71% of the cohort), medium (GAI = 50-99%: 22%), and poor adherence (GAI <50%: 7%). In ordinal regression, the following factors were positively associated with perfect adherence: history of revascularization (odds ratio 1.59, 95% confidence interval 1.27-1.98), prior ICD implantation (2.29, 1.76-2.98), and LV ejection fraction <30% (1.45, 1.19-1.76), whereas age (per 10 years; 0.82, 0.77-0.89), NYHA III/IV (0.15, 0.12-0.18), unknown duration of heart failure (0.69, 0.53-0.89), and antidepressant medication (0.61, 0.42-0.88) were negatively associated with perfect adherence. Better GAI-3 at baseline predicted favorable changes of LV ejection fraction and end-diastolic diameter after 1 year. One-year mortality risk was closely related to GAI-3 in both groups of NYHA functional class I/II (excellent vs. poor GAI-3: 7.2 vs. 14.5%, log rank = 0.004) and class III/IV (13.5 vs. 21.5%, log rank = 0.005). CONCLUSIONS: This large pooled analysis showed that a high level of guideline adherence is achievable in the context of clinical studies. Those receiving and tolerating optimal pharmacotherapy experience a better prognosis. Nevertheless, the implementation of heart failure medication needs further improvement in female and elderly patients, especially those in NYHA functional class >II and patients with LVEF ≥30%.

Low circulating androgens and mortality risk in heart failure.

OBJECTIVE: Deficiency of anabolic sex steroids is common in heart failure (HF). The pathophysiological implications of this phenomenon, however, have not been fully elucidated. This clinical study investigated the significance of low serum androgen levels in HF. DESIGN: Prospective cohort study. Patients and Methods In 191 consecutively recruited men with HF (mean age 64 years; New York Heart Association (NYHA) class I-IV 24%/35%/35%/6%) and reduced (ejection fraction (EF) 40%, n=95) left ventricular function total and free serum testosterone, dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were measured. The median observation period was 859 days. RESULTS: During follow-up 53 patients (28%) died. Whereas total serum testosterone was normal in most patients (91%), free testosterone and DHEAS were reduced in 79% and 23%, respectively. DHEAS and free testosterone, but not total testosterone, were inversely associated with NYHA class (both p<0.01). Lower free testosterone and DHEAS and higher SHBG predicted all-cause mortality risk (hazard ratio (HR) 0.89, 95% CI 0.82 to 0.96 per 1 ng/dl free testosterone, p=0.004; HR 0.95, 95% CI 0.89 to 1.00 per 10 microg/dl DHEAS, p=0.058; and HR 1.18, 95% CI 1.05 to 1.33 per 10 nmol/l SHBG, p=0.006, respectively; adjusted for age and NYHA class). However, further adjustment for carefully selected confounding factors abolished these associations. CONCLUSION: In male HF patients, low serum levels of androgens are associated with adverse prognosis, but this relation is confounded by indicators of a poor health state. The results suggest that low serum androgens develop as a sequel of this progressive multifaceted systemic disorder.

[Treatment of chronic left ventricular failure]. / Behandlung der chronischen Linksherzinsuffizienz.

Rising prevalence and disease-related costs render chronic heart failure a rapidly growing socioeconomic challenge. Guideline-adjusted diagnosis and appropriate therapy are successful in improving mortality, morbidity, functional status and quality of life of patients with chronic left ventricular failure. Corresponding state-of-art recommendations were recently published in the updated European and American treatment guidelines. They determine a stepwise escalation of pharmacological and surgical treatment measures according to increasing disease severity. Still, the complexity of the heart failure syndrome demands to tailor diagnostic procedures and therapy to the patients' individual needs and circumstances.

[52 year-old patient with severe heart failure due to multiple myeloma]. / 52-jähriger Patient mit schwerer Herzinsuffizienz bei multiplem Myelom.

Cardiac amyloidosis represents a prognostically relevant comorbidity in multiple myeloma. We report the case of a patient in whom severe heart failure symptoms as a consequence of cardiac AL-amyloidosis resolved after tandem high-dose melphalan therapy followed by autologous blood-stem cell transplantation. Partial regression of cardiac amyloid deposits and improvement of cardiac function were objectified.

Tissue inhibitor of metalloproteinases levels in patients with chronic heart failure: an independent predictor of mortality.

BACKGROUND: Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in cardiac remodelling. The prognostic utility of TIMP is unknown in chronic heart failure (CHF). AIMS: We investigated the association of plasma levels of soluble MMP-9 and TIMP-1 with clinical, laboratory and echocardiographic parameters and estimated their prognostic value in the prediction of all-cause death. METHODS: MMP-9, TIMP-1, tumour necrosis factor-alpha, and amino-terminal pro-brain natriuretic peptide were measured in 249 consecutively enrolled CHF patients and 74 healthy individuals. RESULTS: After adjustment for age, sex and creatinine, levels of TIMP-1 (1640 vs. 735 ng/ml, P<0.001) but not MMP-9 were elevated in CHF patients compared to controls. During a median follow-up period of 2.5 years, 66 patients (27%) died. In multivariable Cox regression models TIMP-1 but not MMP-9 emerged as an independent predictor of all-cause death (hazard ratio per tertile, 3.5; 95% confidence interval [CI], 2.2-5.1). In addition to the full set of univariately predictive clinical and serological markers, information on TIMP-1 significantly increased the area under the receiver operating characteristic curve from 0.77 (95% CI, 0.71-0.84) to 0.87 (95% CI, 0.82-0.92). CONCLUSION: In stable CHF patients, TIMP-1 but not MMP-9 is of independent and incremental value regarding the prediction of all-cause death.