For this question the results of the CUR domain search were used. In fact, the CUR domain literature was a selection of studies from the basic search done for the whole project done by the project coordinator, and a range of studies (n=14) were selected that provided answers to the question. The results of these studies are described below.

Structured telephone support is one specific type of remote heart failure monitoring. It is monitoring and/or self-care management using simple telephone technology, usually initiated by a healthcare professional (e.g. nurse, physician, social worker or pharmacist) who collects relevant patient data and stores them in a computer. Data can hence be reviewed by the healthcare professional and if necessary, action can immediately be untaken.

Healthcare costs, rapid advances in communication and diagnostic technology, and the availability of low-cost telemedicine equipment are important factors that have significantly contributed to the increasing use of telemedicine for the provision of care {71}. There is a range of different technological modalities for monitoring and/or self-care management. Data may be transferred automatically or manually, through the telephone line, mobile networks or a secure web server to those with expertise in interpreting the data. A distinction is often made between invasive or non-invasive telemedicine interventions for heart failure. Invasive interventions are implanted devices measuring clinical variables which are most often automatically transmitted, whereas non-invasive remote monitoring for heart failure include telemonitoring or structured telephone support {48}. Telemonitoring is specific branch of telemedicine. It is defined as the use of electronic information processing technologies to monitor and transmit clinical data related to patient health status between geographically separated individuals, the choice of data collected is determined by the health problem {99}, it concerns digital, broadband, satellite, wireless or blue-tooth transmission of clinical data {47}. Telemedicine is an approach using remote monitoring by structured telephone support of prognostic factors in order to promote an early identification of clinical deterioration in HF patients, prevent hospital readmission for acute decompensated HF, and avoid further complications {3}. Signs and symptoms reported by patients are collected and subsequently entered and stored in a computer system by the healthcare professional, usually physicians or nurses. The data are then remotely reviewed by healthcare professionals. Appropriate action can be initiated, and deterioration can be rapidly detected, which leads to decrease in unnecessary hospital visits, a decrease in hospital (re-)admissions, an improved quality of life {75}. The highest risk period for hospital readmission is the first few weeks after discharge {90}. Telemonitoring provides the opportunity for the patient to get involved in his own disease management and has the potential to improve patient safety and quality of care {21}.

With particular reference to heart failure (HF), the clinical indications, the clinical benefit, and underlying purposes of telemedicine, of which structured telephone support is one specific intervention, have been clearly outlined in the literature:

The rising healthcare costs, rapid advances in communication and diagnostic technology, and the availability of low-cost telemedicine equipment are important factors that have significantly contributed to the increasing use of telemedicine for the provision of care {71}. A range of different technological modalities for monitoring and/or self-care management exists in telemedicine.

Technologies vary from devices such as:

-implantable pacing, defillibrator technologies or cardiac resynchronization devices (remote monitoring by integration of signals from several monitored variables);

-structured telephone support (normal telephone, usually conducted by nurses who call patients to provide monitoring of the patients’ signs and symptoms, supported by a computer that collects and stores the data);

-videophone or video-consulting, interactive voice response systems (a computer voice guides the patient to press phone keys in response to questions);

-telemonitoring in which clinical data are electronically transmitted to a health-care team including telephone touch-pad-based telemonitoring modalities and website-based telemonitoring modalities {75},{14}.

In telemonitoring data may be transferred automatically or manually, through the telephone line, the GSM or a secure web server to those with expertise in interpreting the data, whereas in structured telephone support a healthcare professional conducts the call with the patient to gather data that is entered in a computer system. A distinction is often made between invasive or non-invasive telemedicine interventions for heart failure. Invasive interventions are implanted devices measuring clinical variables which are most often automatically transmitted, whereas non-invasive remote monitoring for heart failure include telemonitoring or structured telephone support {48}.

Telemonitoring is a specific branch of telemedicine. It is defined as the use of electronic information processing technologies to monitor and transmit clinical data related to patient health status between geographically separated individuals. Telemonitoring may be continuous or intermittent, usually event-triggered, and the choice of data collected is determined by the health problem of the individual patient {99}. As such, in specialized telemonitoring devices and telephone touch-pads for data entry, patients need to enter their signs, symptoms, and other necessary clinical data such as blood pressure and heart rate {75}. It concerns digital, broadband, satellite, wireless or blue-tooth transmission of clinical data for remote follow-up of a patient over a longer period of time. Home telemonitoring is the remote care delivery or monitoring between a healthcare provider and a patient at a distant location {47}. Structured telephone support, as subject of the current Core HTA, is one specific type of remote heart failure monitoring. It is monitoring and/or self-care management using simple telephone technology, usually initiated by a healthcare professional (e.g. nurse, physician, social worker or pharmacist), in which data is stored on a computer {47}.

Structured telephone support as one particular telemonitoring intervention comes along with several practical general advantages. One important advantage of structured telephone support is an improvement of the observation of patients implying long-term monitoring to detect changes in the patients’ condition and thereby having the potential to improve outcomes {99}. Structured telephone support may be particularly suited to make care more accessible to a larger number of patients including those constrained by geography, transport or infirmity {75},{14}. It thereby can also meet the needs of healthcare systems regarding the shortage of healthcare professionals and increasing costs which are problems many countries are facing {92}. It is a patient management care, also labelled as integrated care approach, that ensures appropriate monitoring and treatment of an increasing number of chronically ill patients at a relatively low cost {91}. Structured telephone support shifts health care out of a clinical setting into the patient’s home environment or another non-hospital setting facilitating supported self-care, giving the patient enhanced autonomy and control of their disease. Structured telephone support can assist patients in self-monitoring their signs and symptoms and be individually tailored and flexible {11}, {47}, and often includes education or self-care training {25}. It is accepted by patients and likely to be patient-friendly and to enable daily contact with patients without the need for face-to-face contact {47}, {48}, {95}. The underlying purpose is to provide health professionals with accurate and timely information required to remotely detect any deviant health parameter and complications associated with the disease, before an emergency or a scheduled face-to-face follow-up visit is required. It is not an emergency system but helps to generate a fast response. Participation of patients in a telemonitoring programme on a daily basis holds the potential favorable effect to improve health behaviors including adherence to medical recommendations {8},{99} {24}.

Structured telephone support as one particular telemonitoring intervention comes along with several advantages that apply especially to cardiac patients, but that may also apply to patient groups with other chronic diseases including diabetes, chronic obstructive pulmonary disease, asthma and hypertension {91},{118},{62}. The systematic review of Paré et al. {91} revealed evidence concerning the reliability and accuracy of home telemonitoring as an approach to patient management among patients with these chronic diseases, in particular in the cases of pulmonary conditions and HF. The positive effects of telemonitoring in the above named chronic diseases (including HF) primarily result from the fact that telemonitoring allows for frequent patient follow-up, and as a result warning signs of the health state can be detected and appropriate action can be initiated on time. On the other side, telemonitoring has revealed to promote an improvement of patients’ self-management and treatment adherence {92}. According to Woottoon 2012 {118}, the main aims of telemonitoring are to support integrated care in chronic disease management by providing information and education in order to improve patients’ self-management, facilitating contact with the healthcare professional and improving electronic records {118}.

In HF, telemedicine is an approach using remote monitoring of prognostic factors by structured telephone support in order to promote an early identification of clinical deterioration in HF patients, prevent hospital readmission for acute decompensated HF, and avoid further complications {3}. Prognostic factors that are monitored include weight, blood pressure, pulse oximetry, respiratory rate, body temperature, oxygen saturation, electrocardiograph (ECG) changes, fluid status, ankle swelling over time, infection, intrathoracic impedance, arrhythmias, heart rates during rest and exertion {3}, but also other factors including self-care, education, lifestyle modification, and medicine administration {47}. As already mentioned, one favorable consequence of structured telephone support is that may promote HF patients’ treatment adherence and self-management {8},{99}.

With frequent structured telephone support, signs and symptoms reported by patients are collected and subsequently entered by the healthcare professional who is talking over the phone with the patient in a computer system. The data can then be remotely reviewed by healthcare professionals, usually physicians or nurses. If the clinical data do not correspond with agreed parameters or in case complications are observed by an increase in the severity of HF signs and symptoms, healthcare professionals are alerted. Appropriate action can be initiated, and deterioration can be rapidly detected and addressed, for example by adjusting medication or arranging a clinical visit. A timely medical care response or improvement in treatment adherence is prompted and this, in turn, may potentially lead to a decrease in unnecessary hospital visits, a decrease in hospital (re-) admissions, an improved quality of life, fewer events and deteriorations for HF, and reduced healthcare costs {75}. Because the highest risk period for hospital readmission is the first few weeks after discharge, it is suggested that daily telephone support is of particular high benefit during that period {90}. Last but not least, structured telephone support as one particular telemonitoring intervention has the potential to improve patient safety and quality of care {21}.

For this AE the results of the basic search were used,

Additionally the following article was used from handsearch:

MAST REgioNs of Europe WorkINg toGether for HEALTH (Grant Agreement No 250487). D1.12 v1.5 Renewing Health Final Project Report - Public

All provided text-parts about variations in different settings were used, mainly provided descriptively in the studies.

Most studies report care provided by a multidisciplinary team, but a great deal of heterogeneity regarding the professionals involved was described. Collaboration between primary care and secondary care was scarcely reported. In almost all the studies, nurses played a coordinating or leading role, but description of the specialization of clinical background were lacking. Almost all programmes also had physicians involved, which could be cardiologists, and/or primary care physicians or other specialists such as geriatricians or internists. Additionally, other professionals (psychologist, dietician, physical therapist, social worker, pharmacist) were involved in the programmes, mostly as a member of the multidisciplinary team or occasionally as the main provider of an intervention (e.g. a pharmacist). A different variation of systems for telemonitoring was found, ranging from assessment of symptoms and/or vital signs to data transmission and automatic alarms. {51}

Substantial heterogeneity among studies was noted {119 }, the content of the telemedicine interventions vary between patient groups and with regard to duration and content.

Among the included 15 reviews 188 references were cited about telemedicine for patients with heart failure. 69 (37 %) of these references are from Europe, 30 (16 %) are from South America, Asia and New Zealand, and 89 (47 %) are from the US.

There were 62 studies from Europe cited in the reviews. Out of the 62 European studies, 16 mentioned educational strategies within the telemedicinal programme. The involved persons in the educational programmes were cardiologists (3 studies), multidisciplinary teams at least for the care plan (25 studies), physician-/primary care led (1 study each), and nurse-led (4 studies) programmes. The other reviews did not mention their specific programme used (32 studies).

In 17 studies, the transfer mode was via telephone/ cell phone transmission, in 4 studies through implantable devices, 1 study described interactive videoconferencing, transtelephonic monitoring, 1 study described hospital-at-home service, 2 studies just described non-invasive telemonitoring, and in 36 studies the transfer mode was not clear.

There are differences in the level of complexity among the technologies and decision systems within telemedicine.{14} Many studies (i.e. n=69, 99 % of the included studies in {51}) report care provided by a multidisciplinary team, but the involved professionals are heterogeneous. Scarcely reported is the collaboration between primary care and in-hospital care provider. In almost all the studies, nurses played a coordinating or leading role, described as homecare nurses, hospital nurses, HF nurses, cardiac rehabilitation nurses, research nurses, practice nurses, and/or district nurses. The description of the specialization of clinical background was lacking. Physicians were involved in almost all programmes, described as cardiologists, primary care physicians, or other specialists such as geriatricians or internists. Additionally, other professionals (psychologist, dietician, physical therapist, social worker, pharmacist) can be involved in the programmes, as a member of the multidisciplinary team or occasionally as the main provider of an intervention (e.g. a pharmacist). The different variations of systems for telemonitoring range from assessment of symptoms and/or vital signs to data transmission and automatic alarms. {51}Substantial heterogeneity among studies was also noted in regard to intervention components, methodologic quality, target population, clinical setting, telemedicine technology, outcomes assessed, personnel involved, and other key factors {52}, There was also a variation within the monitored parameters, the HF selection criteria and lacked detail in the components of the RM (remote monitoring) care packages and usual care.{90}The content of the telemedicine interventions also vary between patient groups and in duration and content. Some include videoconferencing between patients and healthcare professionals, others include monitoring of disease-specific health data by use of medical devices, and some include elements of health coaching. {119}

The used strategies described as telemonitoring for the European studies in the used reviews are listed in the table at appendix 1.  

Three studies out of the basic literature search provided some information relating the selection of patients for telemonitoring.

Three of the reviews reported eligibility and exclusion criteria for patients included in the studies, but there was no answer on who decides or who should decide to use telemedicine for what patient.

One could take the eligibility criteria used in the studies as a surrogate for the decision basis: clinical severity aspects, aspects of positive attitudes towards self-management, and criteria for acceptance and compliance. The used criteria within the studies are listed below.

Several exclusion criteria were used in the studies. Most commonly patients were excluded from the studies in case they:

-had a moderate or serious cognitive, visual, or physical disability {92};

-did not own a phone or who had a life expectancy measured in months rather than years {92};

-were discharged to a long term care facility {42};

-had some form of cognitive impairment or psychiatric disorder {42};

-had a terminal disease or severe co-morbidity {42}.

When determining eligibility criteria, it cannot be denied that some patients appear to benefit more than others. Several studies have suggested that the beneficial effects on state of health are observed mostly among patients:  

-whose state of health is considered serious (e.g., the studies by Kwon et al {66} and Trappenberg et al {108}); in {92};

-who want to play an active role in the management of their illness (eg, the studies by Madsen et al {72}, Rickerby and Woodward {97}, DelliFraine and Dansky {18}, and Hopp et al {43}) in {92};

-who are interested in using this type of technological device (eg, the studies by Vähätalo et al {109}, and Madsen et al {72}) in {92};

-with a mean age varied between 56–86 years {42} or 59-82 years {25};

-with a proportion of men from 27–99  % among the studies {42} {25};

-with recorded baseline ejection fractions, with trial means varying from 22–43  % {42};

-with New York Heart Association functional class > II {50} {42} {25};

-with a proportion of patients with coronary artery disease or prior myocardial infarction (MI) ranged from 27 percent to 61 percent in most trials {25}.

In terms of the technology, important acceptance criteria are

-the user-friendliness of the device installed in the home and its nonintrusiveness in the lives of patients, particularly for the youngest patients {92};

-level of technological skill {92};

-level of education {92};

-professional constraints {92} ;

-lifestyle {92};

-having a visual or motor deficit {92}.

Eligibility to new technology depends on an assessment of the general practitioner of a patient’s condition and the patient's willingness and ability to participate. Access to new technologies depends on support of healthcare providers. In real-world settings, patient selection will be critical for the acceptance and compliance with the programme. Patient selection criteria might include the degree to which the patient is willing to incorporate these technologies into their care or patients at high-risk {40}. Having  an access to a touchtone telephone is an essential inclusion criterion {1} . By Dunagan et al {10} cognitive or psychologic impairment as well as inability to hear and understand English spoken over the telephone were included as non-eligibility criteria.

Three of the reviews reported eligibility and exclusion criteria for patients included in the studies, but there was no answer on who decides or who should decide to use telemedicine for what patient.

One could take the eligibility criteria used in the studies as a surrogate for the decision basis: clinical severity aspects, aspects of positive attitudes towards self-management, and criteria for acceptance and compliance. The used criteria within the studies are listed below.

Several exclusion criteria were used in the studies. Most commonly patients were excluded from the studies in case they:

-had a moderate or serious cognitive, visual, or physical disability {92};

-did not own a phone or who had a life expectancy measured in months rather than years {92};

-were discharged to a long term care facility {42};

-had some form of cognitive impairment or psychiatric disorder {42};

-had a terminal disease or severe co-morbidity {42}.

When determining eligibility criteria, it cannot be denied that some patients appear to benefit more than others. Several studies have suggested that the beneficial effects on state of health are observed mostly among patients:  

-whose state of health is considered serious (e.g., the studies by Kwon et al {66} and Trappenberg et al {108}); in {92};

-who want to play an active role in the management of their illness (eg, the studies by Madsen et al {72}, Rickerby and Woodward {97}, DelliFraine and Dansky {18}, and Hopp et al {43}) in {92};

-who are interested in using this type of technological device (eg, the studies by Vähätalo et al {109}, and Madsen et al {72}) in {92};

-with a mean age varied between 56–86 years {42} or 59-82 years {25};

-with a proportion of men from 27–99  % among the studies {42} {25};

-with recorded baseline ejection fractions, with trial means varying from 22–43  % {42};

-with New York Heart Association functional class > II {50} {42} {25};

-with a proportion of patients with coronary artery disease or prior myocardial infarction (MI) ranged from 27 percent to 61 percent in most trials {25}.

In terms of the technology, important acceptance criteria are

-the user-friendliness of the device installed in the home and its nonintrusiveness in the lives of patients, particularly for the youngest patients {92};

-level of technological skill {92};

-level of education {92};

-professional constraints {92} ;

-lifestyle {92};

-having a visual or motor deficit {92}.

Patient self management of chronic conditions, both the disease and the symptoms, is an aged practice that is accelerating and disseminating throughout the world, fueled in part by home-based and portable technologies. Ethically problematic assumptions have the potential to harm some patients and unnecessarily exclude others from self management. A new and higher standard than the current provider-based practice; that readiness to learn, literacy and intact cognitive function are frequently not essential to competent patient self management; that patients, however, are still excluded from it based on apparent defects in these characteristics; and that quality control standards for self management are essential but are not sufficiently rigorous. Barriers to improved outcomes from self management include the virtual absence of objective measures of patient competence to self manage, and of explicit, publicly available and well-argued descriptions of risk and benefit {1450}.

In clinical trials included the selection of patients was made by the researchers on the basis of specific inclusion criteria. For example, in all STS RCTs reviewed by Inglis et al {490}, having access to a touchtone telephone was an essential inclusion criterion. In a RCT of telephone or videophone communication vs. UC {1}, a Mini Mental Status Examination Score above a certain threshold and a phone line at home were among the inclusion criteria. In the clinical trial reported by Dunagan et al {10} cognitive or psychologic impairment as well as inability to hear and understand English spoken over the telephone were included as non-eligibility criteria.

In real-world settings, patient selection will be critical for the acceptance and compliance with the programme. Patient selection criteria might include the degree to which the patients are willing to incorporate these technologies into their care or, patients at high-risk could be a main target group for these programmes {40}.

Eleven studies out of the basic literature search and one study from an additional handsearch provided information to answer this question.

Generally, telemedicine and telemonitoring can be seen as relatively new, currently as an adjunct to current care with the chance of more patient-self-care-involvement and improved quality of therapeutic monitoring, but without a clear unique idea where it should lead to and how it should be implemented.

One of the included studies provides a historical overview of the published studies, starting with 1987, growing in the late 1990s, but most published after 2000, mainly from the US. The study mentions that: „The data show that home telemonitoring programmes have appeared quite recently. Even though the first study on this subject was published in 1987, most early projects to be described in the literature began to appear in the early 1990s. Studies published between 1991 and 1995 represent 6 % of the total sample. The number of published studies then grew in the second half of the decade (1996 to 1999), representing 15 % of the sample. The number then increased significantly: more than three quarters of the studies in the sample were published after 2000. The data also show that 45 % of the studies were carried out in the United States, approximately a third were conducted in Europe, while 6 % were conducted in Asia and in Canada. Finally, almost three quarters of the studies in our sample were RCTs, both small and large.“ {92}, 2010

Giamouzis et al. (2012) describes telemedicine as a novel diagnostic modality in 2012{31};  Sousa et al. as a novel tool {102}, 2014.

Eight of the included reviews try to look at the indicators for novelty and how they lead to a novel attitude – like including the patient - and new settings – like different patient- and physician roles - of health care. They still describe telemedicine as „changing modality“ {15}, „promising“ {91}, 2007, „complementary“ {99}, 2010, „potentially“ {35}, 2011, „a modality to improve care“ {34}, 2012, and a common insecurity about what exactly is defined as telemedicine and what kind of programmes were modified into telemedicine (like disease management programmes which are technically supported) seems to occur. The importance and necessity of individual self-care in the overall HF management is recognized {96}, 2012, but currently only a relatively small proportion of HF patients have access to such programmes {102}, 2014. Telemonitoring moves patient care out of a clinical setting shifting the burden of care to the patient’s home, but also giving the patient enhanced autonomy and control {47} in {95}, 2014.

Remote monitoring is still described as an adjunct to current out-of-hospital management of advanced heart failure {63} and is still not widely adopted due to a number of social, technological and reimbursement issues. Remote monitoring will not replace face-to-face clinical review, but it will be part of the solution to the increasing numbers of patients with heart failure and/or an implantable device.{14}

For this AE the results of the CUR domain search were used. Most of the studies and literature reviews selected for the CUR domain provided some kind relevant information on the target population of the intervention. The two latest published guidelines of the European Society of Cardiology (ESC) on the diagnosis and treatment of HF and the website of the ESC were additionally consulted to find relevant answers to this AE.

Structured telephone support may not be suitable for every patient diagnosed with HF. According to Koehler et al. 2011 {64}, telemonitoring is particularly suitable for patients who are recently hospitalized due to HF, medically unstable, or classified being in the NYHA Class II and III. Koehler also recommends performing telemonitoring during the 12 event-free months after hospitalization for HF {64}. Since structured telephone support is one specific intervention of telemedicine, these eligibility criteria equally apply.

Guidelines of the ESC recommend remote monitoring of patients reporting symptoms (including drug adverse effects) and signs of HF (Class I recommendation, Level of Evidence: C) {19}.

Patients with cognitive impairment, a mental illness, a life expectancy less than one year, language barrier, hearing impairment, or another chronic disease are often not eligible for structured telephone support (Polisena et al., 2010) {93}. This has been confirmed by Paré et al. 2010 {92} who outlined on the basis of their systematic review on the clinical effects of home telemonitoring in the context of diabetes, asthma, HF and hypertension that telemonitoring likely to not be suitable for everyone, because most studies excluded patients with a moderate to severe cognitive, physical, visual or hearing disability. Patients who did not own a phone or who a very short life expectancy (less than 1 year) were often excluded as well. The beneficial effects on state of health are observed mostly among patients whose health state is rather serious {92}. However, the fact that certain groups have been excluded from studies does not mean that telemonitoring may not be suitable for them. According to the current literature this remains unknown and further research may identify if telemonitoring is also suitable for these patients.

In this current assessment of structured telephone support for adult patients with chronic heart failure, the target population concerns patients who have signs or symptoms of HF, or an underlying non-diagnosed abnormality of the cardiac structure that is likely to lead to HF.

Further considerations for the target population: According to the large number of studies that have been conducted on the clinical effectiveness of telemonitoring in HF patients, including structured telephone support, the appropriate target population generally concerns:  

-the elderly, with a definitive clinical diagnosis of HF;

-with a mean age generally around 70 years old (patients may also be significantly younger or older);

-or with chronic HF;

-often who have had a cardiovascular hospitalization or a hospitalization for HF within the previous 12 months;  

-who have been discharged to home;

-often with moderate or severe symptoms of HF (New York Heart Association, NYHA class II-IV), a LVEF ≤ 30 %;

-who are administered diuretics, ACE inhibitors and beta blockers.

In this group, the highest benefit of structured telemonitoring may be reached.

Although the basic search for the CUR domain was used to answer this question, no article of the basic search was selected to be relevant for this assessment element. Therefore, a manual search was done to find relevant information about the incidence and prevalence of the health condition as published in evidence-based guidelines and (international) reports on the HF epidemiology. European and American guidelines for the diagnosis and treatment of acute and chronic HF were consulted by doing a manual search on the website of the ESC and the American Heart Association (AHA), and the references of the ESC guidelines published in 2008 and 2012 and the AHA practice guideline published in 2013 were reviewed. These guidelines led occasionally to an additional article that was relevant for this question. Moreover, the 2015 Update of Heart Disease and Stroke Statistics of the AHA was reviewed. The website of the ESC was additionally searched for relevant studies that have been published so far on the epidemiology of HF worldwide and in developed and developing countries (search terms epidemiology OR incidence OR prevalence AND heart failure). The additional search resulted in 22 additional relevant studies. The searches for the additional studies and guidelines were additionally conducted the 06th of January 2015 by one of the investigators. Two additional studies were included during the consultation phase.

Although various studies have been conducted in the past to capture the epidemiology of HF, there is still a scarcity of epidemiological data. The absence of gold-standard criteria for the diagnosis of HF, together with a lack of agreement on a definition of HF itself, explains why studies fail to use a uniform assessment of HF. This has led to considerable variations in the estimates of the incidence and prevalence of HF. Moreover, the highly selected patients and retrospective analysis as present in the majority of the clinical trials is likely to bias the real prevalence and incidence numbers. The epidemiological data presented is further limited to hospitalized patients who do not provide information on non-diagnosed patients with mild and asymptomatic HF {116}. In addition, other non-cardiac related conditions such as diabetes, obesity, chronic obstructive pulmonary disease or a restrained physical fitness may mask HF since these chronic diseases may be viewed as the primary diagnosis. To assess the actual epidemiology of HF, random samples in the general population may be useful using validated surveys, physical examinations and objective methods to identify HF and the underlying cardiac dysfunction {82}. In consequence, available epidemiological data in HF are not comprehensive since they only describe a fraction of patients with this syndrome.

Cardiovascular disease (CVD) is the most common cause of death worldwide, being responsible for almost 30% of all deaths. In Europe CVD is responsible for 45% of all deaths equating to >4 million deaths per year, causing almost twice more deaths as cancer. Although mortality from CVD has decreased substantially in the past decade, there are wide inequalities in terms of death but also in terms of rates of treatment between (European) countries (Nicols et al., 2014; Townsend et al., 2015). {123,124} The most common forms of CVD are coronary heart disease, stroke and HF. HF is a large and global public health problem that will become more important with the aging of the world population. The number of patients with HF is predicted to increase considerably in countries with fast ageing populations. Up to one person in five is expected to develop HF at some point in their life in economically developed countries {70}. In 2007, it was already estimated that approximately 1–2 % of the adult population in developed countries had HF and that the incidence approached on average 5–10 per 1000 persons per year with a significantly higher incidence in higher age groups {82}.

In 2011, it was estimated that 26 million adults worldwide were living with HF {6}, leading some to describe it as a global pandemic {2}. Of these patients at least 15 million are European {19}, whereas almost 7 million Americans ≥ 20 years of age have HF {120}. According to the AHA, at least 850.000 patients are yearly newly diagnosed with HF in the US with the incidence approaching 1 per 100 people 65 years of age and older. According to projections of the AHA, the prevalence of HF will increase 46 % from 2012 to 2030 {83} revealing that at least an additional 3 million adults will have HF {120}. Currently, at least 5 million Americans have a clinically manifest HF {115}. Data on the incidence and prevalence of HF in the developing world are largely absent, but it is estimated that there is also an increasing number of patients with HF in the developing countries due to the emerging pandemic of cardiovascular diseases {78}. However, it is known that unlike in the US and Europe, individuals in sub-Saharan Africa countries are diagnosed with HF at a significant younger age. HF is common in South Africa, and approximately half of patients with newly diagnosed cardiovascular disease have HF, whereas only 10 % have coronary artery disease {101},{16}. Across Asia, the prevalence of HF ranges between 1.3 % and 6.7 %. According to a recent study on the global burden of ischemic heart disease {80}, HF in men was most prevalent in North America, Oceania, and Eastern Europe (> 5 per 1000). In women, the prevalence of HF was highest in Oceania, North America and North Africa and the Middle East (4.5 per 1000). HF was lowest in west sub-Saharan Africa for both men and women (< 1 per 1000). Many populations are facing a “double HF burden” caused by communicable and non-communicable diseases {80}.

HF is a condition that becomes more common with increasing age. In North America and Europe, persons 50 years of age or under are hardly ever found to have HF {32},{7},{107}, and more than 80 % are 65 years of age or older  {6}. Hence, particularly in those older than 50 years of age the prevalence and incidence increase progressively with age. In 2007 the prevalence was estimated to be 10-20 % in persons with the age between 70 and 80 while it was rising significantly to ≥10 % among persons 70 years of age or older {82}. In the Dutch Rotterdam study, the prevalence of HF was 1 % in the age group of 55-64 years, 3 % in the age group of 65-74 years and 13 % in the age group of 75-85 years {81}. Moreover, according US estimates, the remaining lifetime risk for development of new HF remains at 20 % at 80 years of age, even in the face of a much shorter life expectancy {83}.  

Overall, the prevalence of systolic HF and diastolic HF is estimated to be equal between men and women. According to the ESC (2012), at least half of patients with HF have a low or reduced ejection fraction. HF with a preserved ejection fraction or diastolic HF is present in approximately 50 % the patients with HF {77},{29}. In younger age groups, systolic HF occurs more frequently in men than in women because myocardial infarction occurs at an earlier age in men. Diastolic HF is more common in the elderly, in women, in individuals with longstanding hypertension, diabetes, renal failure, anemia, and atrial fibrillation {19}. Studies show that the accuracy of the diagnosis of HF by clinical means alone is often inadequate. This applies particularly to female, elderly, and obese patients, leading to a potential underrepresentation of the patients who have HF {106},{60},{77}.

The globally increasing prevalence of HF is not merely due to the ageing of the population. It is also due to improvements in the treatment of acute coronary syndromes, effective prevention in those at high risk or those who have already survived a first coronary event, a longer survival of cardiac patients and HF patients, and the increasing epidemiology of cardiovascular diseases in the developing countries  {84},{100},{116}. An increase in risk factors for HF such as diabetes, sedentary behavior and obesity also contribute to the increasing pool of HF patients. Factors that on the other hand decrease the incidence of HF are a decline in the number of new cases with myocardial infarction, a decline in the severity of acute myocardial infarction and the improvement of care  {40},{85}. The improvement of care for hypertension and coronary artery disease, particularly in Western Countries, also account for a decreasing incidence {86}.

The basic search for the CUR domain was used to answer this question with 1 article. Moreover, a manual search was done to find relevant information about the HF syndrome as published in evidence-based guidelines and in 8 additional scientific studies on HF. European and American guidelines for the diagnosis and treatment of acute and chronic HF were consulted by doing a manual search on the website of the ESC and the AHA, and the references of the ESC guidelines published in 2008 and 2012 and the AHA practice guideline published in 2013 were reviewed and these led occasionally to an additional article that was relevant for this assessment element. Moreover, the ICD-10 of the World Health Organization was consulted. The searches for the ICD-10 and guidelines were additionally conducted the 06th of January 2015 by one of the investigators.

HF is not a disease but a collection of signs, symptoms, and pathophysiology {86}. HF is generally characterized by an underlying structural abnormality or cardiac dysfunction that impairs the ability of the left ventricle to either fill with blood or contract to eject blood, especially during physical activity. Its prevalence, incidence, and clinical outcome are related to a range of cardiovascular and non-cardiovascular conditions that cause cardiac impairment {86}. HF is associated with significant reduced quality of life, morbidity, and mortality. Moreover, it puts a considerable burden on the healthcare systems around the globe, largely due to high hospital admission and readmission rates, and long hospital stays. In fact, HF patients have a high risk of readmission especially in the first weeks after hospital discharge, with 20-30 % of the patients being readmitted with a month. This rises up to 60 % after six months of hospital discharge {90}. 

According to the ESC, HF is a complex clinical syndrome in which patients have typical symptoms and signs resulting from an abnormality of cardiac structure or function. Although often life-threatening, typical symptoms and signs resulting from the abnormality of cardiac structure or function (as present in HF), lead to failure of delivering oxygen {77}. The most typical symptoms of HF are shortness of breath at rest or during exertion, fluid retention reflected in pulmonary congestion or peripheral edema (ankle swelling), fatigue, and dizziness  {19},{75}. The most typical clinical signs HF patients may have are tachycardia, tachhypnoa, pleural effusion, hepatomegaly, elevated jugular peripheral edema, pulmonary edema, venous pressure, pulmonary crackles, fluid overload, and displaced apex beat. According to the ESC guideline published in 2008, most definitions emphasize the need for both the presence of HF symptoms and physical signs of fluid retention {19}.

There is no single diagnostic test for HF but it is rather a clinical diagnosis based on a careful history and physical examination {115}. The diagnosis of HF can be difficult when relying solely on symptoms and signs. Objective evidence of an abnormality of the cardiac structure is required. Many of the symptoms of HF are of limited diagnostic value to discriminate between HF and other health abnormalities because they are non-specific. One typical symptom of HF is peripheral edema, but because it has other causes as well, it is particularly non-specific. More specific symptoms (i.e. orthopnoea and paroxysmal nocturnal dyspnoea) are less common, especially in patients with milder symptoms, and are, therefore, insensitive. More specific signs, such as elevated jugular venous pressure and displacement of the apical impulse, are hard to detect and, thus, less reproducible (i.e. agreement between different physicians examining the same patient may be poor) {74},{89},{27},{55}. Symptoms and signs may be difficult to identify and interpret in specific patients, such as obese individuals, elderly, patients with pulmonary disease, and patients with a poor physical condition or ischemia {38}. Many of the HF signs result from sodium and water retention (e.g. peripheral edema). These symptoms may, however, be absent or lead to quick symptomatic improvements in patients receiving diuretic therapy. Therefore, these symptoms are also not specific. In case of uncertainty, a favorable response to treatment directed towards HF is warranted. Nonetheless, a clinical response to treatment for HF is not sufficient for the diagnosis, but it can aid when the diagnosis remains unclear after appropriate diagnostic tests. To the diagnosis of HF, an underlying cardiac cause has to be demonstrated. Conditions that cause pressure overload (eg. hypertension, aortic stenosis), idiopathic dilated cardiomyopathy, and abnormalities of ventricular diastolic function, heart valves, pericardium, endocardium, heart rhythm, and conduction can cause HF. However, HF usually results from myocardial infarction causing an impaired systolic left ventricular function {77}.

Table 1 Symptoms and signs typical for heart failure

Systolic versus Diastolic Heart Failure

HF is mainly described using a measurement of the left ventricle ejection fraction (usually measured by echocardiography or, in a minority of cases, with use of radionuclide technique or MRI). The ejection fraction has a prognostic value since a reduced ejection fraction indicates a poorer survival. Most clinical trials select patients based upon the ejection fraction. A normal ejection fraction in healthy subjects is generally considered to be > 50 % {77}. 

A distinction is frequently made between systolic and diastolic HF. Most patients have both abnormalities of systolic and diastolic dysfunction {115}. The weakened ability of the left ventricle to contract and empty is known as ‘systolic dysfunction’. In patients having left ventricular systolic dysfunction, the heart is unable to pump sufficient blood into the body circulation during systole due to an inability to pump efficiently {19},{77}. Left ventricular systolic dysfunction is a complication of myocardial infarction that greatly increases the risk of HF. Besides myocardial infarction leading to left ventricular systolic dysfunction and subsequent HF, myocardial infarction may lead to papillary muscle dysfunction and mitral regurgitation or provoke arrhythmias, like atrial fibrillation, which in turn leads to HF. In other patients, preexisting myocardial ischemia may impair myocardial relaxation impeding the left ventricle to dilate {12}. Echography is most often utilized to assess left ventricular systolic dysfunction or systolic HF, which according to the ESC signifies a reduced ejection fraction of ≤ 35 %. In fact, the heart ejects a smaller fraction of a larger volume while stroke volume is maintained by an increase in the end-diastolic volume because the left ventricle dilates. The major clinical trials have also included patients with systolic HF with a reduced left ventricular ejection fraction (HFREF) ≤ 35 %. Nevertheless, uncertainties concerning the appropriate threshold remain {19},{77}.

Generally speaking, diastolic HF is HF with an inability of the heart to relax normally at diastole. As a result, it does not fill properly. The syndrome is an impaired filling of the left ventricle in response to a volume load, despite normal ventricular contraction. It is characterized with a preserved left ventricular ejection fraction (HFPEF) which signifies an ejection fraction of > 40-45 % {19},{77}. HFPEF has, however, also been classified as EF 50 % and ≥ 55 %, leading to variable prevalence rates of HFPEF which generally is around 50 % {115}. In HFPEF, patients have a normal left ventricular function, i.e. the heart contracts normally, but higher filling pressures are needed to obtain a normal end-diastolic volume of the left ventricle. These patients do not have an entirely normal ejection fraction but also no major reduction in systolic function. Therefore, these patients are considered to have HF with a ‘preserved’ ejection fraction. More recent trials have included diastolic HF patients with an ejection fraction > 40-45 % and no other causal cardiac abnormality. Patients with an ejection fraction varying between 35 % and 50 % probably have a mild ‘systolic dysfunction’ and represent a grey area. The diagnosis of HF with a ‘preserved’ ejection fraction is difficult because potential non-cardiac causes may account for the patient’s symptoms (e.g. anemia or chronic pulmonary disease). Nevertheless, most have evidence of diastolic dysfunction, which is generally accepted as the likely cause of HF in these patients. Therefore, the term diastolic HF is common to describe this specific syndrome of HF {19},{77}.

In sum, patients with diastolic HF have symptoms and/or signs of HF and a preserved left ventricular ejection fraction (LVEF) > 40–50 % and patients with systolic HF have symptoms and/or signs of HF and a reduced left ventricular ejection fraction (HF-REF) ≤35 %. There is no agreement concerning the cut-off for preserved versus reduced EF {19},{77}.

The current 10^th edition of the International Classification (ICD) system classifies HF as an intermediate, not underlying cause of death. It describes HF as congestive HF including congestive heart disease and right ventricular failure. HF is also defined as left ventricular failure including cardiac asthma, left HF, and heart disease (unspecified) or HF with edema of lung and pulmonary edema. HF is further defined as the incidence of HF due to rheumatic heart disease, hypertensive heart disease, ischemic heart disease and inflammatory heart disease. Complicating abortion or ectopic or molar pregnancy, obstetric surgery and procedures are excluded from the classical definition of HF by the ICD-10. Moreover, HF due to hypertension (with renal disease), HF following cardiac surgery or due to presence of cardiac prosthesis, and neonatal cardiac failure are excluded {113}.

• The basic search for the CUR domain was used to answer this question article selected to be relevant for this assessment element.

   

• Moreover, a manual search was done to find relevant information about risk factors and determinants of the HF syndrome as published in evidence-based guidelines and in additional scientific studies on HF. European and American guidelines for the diagnosis and treatment of acute and chronic HF were consulted by doing a manual search on the website of the ESC and the AHA, and the references of the ESC guidelines published in 2008 and 2012 and the AHA practice guideline published in 2013 were reviewed and these led occasionally to an additional article that was relevant for this assessment element. Moreover, the 2015 Update of Heart Disease and Stroke Statistics of the AHA and the report “Heart failure: preventing disease and death worldwide” published by the World Heart Failure Alliance was also consulted for this AE were reviewed. Finally, an additional search on the website of the ESC was done with the key words “risk factors” AND “heart failure” resulting in the studies listed below, which occasionally led to an additional reference in order to refer to the original study. The additional searches were conducted the 06th of January 2015 by one of the investigators.

Risk factors for HF vary from lifestyle factors (e.g. smoking, alcohol intake, sedentary lifestyle and a unhealthy diet) to consequences of a unhealthy lifestyle (diabetes, obesity, arteriosclerosis) to socio-demographic factors (e.g. higher age, socio-economic status) and hereditary factors (e.g. race, hypercholesteria, atherosclerosis) and disease history (e.g. history of atrial fibrillation, presence of hypertension, diagnosis of CHD, chemotherapy, viral infection) and more specific biological factors (e.g. higher levels of hematocrit, increased circulating concentrations of resistin, cystatin C).

Many developing countries are now facing the similar risk factors due to a shift towards a Western-type lifestyle. Risk factors for hospital (re-) admission are highly comparable to the risk factors for developing a HF.

A greater survival has been noted for patients with established CHF (“reverse epidemiology”,) who have obesity, hypercholesterolaemia and hypertension.

Coronary artery disease notably increases the likelihood of developing HF. According to Hellermann et al. (2003) {40}, at least one third of patients will experience HF in less than 10 years after having experienced a myocardial infarction, especially those who have left ventricular systolic dysfunction during admission {40}. Although people who have hypertension have a smaller likelihood of developing HF than those who have had a myocardial infarction, hypertension contributes considerably to the population burden of HF as it is much more prevalent than myocardial infarction {69}. Hypertension leads to a myocardial overload and thus to left ventricular systolic and diastolic dysfunction that in turn can lead to congestive HF. Especially an elevated level of systolic blood pressure is a major risk factor for HF. Data suggest that patients with hypertension have a particularly high incidence of left ventricular diastolic dysfunction {115}. Obesity, caused by a sedentary behavior and an unhealthy diet and increasingly present in Western societies, doubles the likelihood of developing HF after adjustment for associated risk factors {56}. Another risk factor associated with obesity is the metabolic syndrome signifying abdominal adiposity, hypertriglyceridemia, a high level of low high-density lipoprotein in the blood, and fasting hyperglycemia {115}. Diabetes also increases the risk for developing HF. Valvular abnormalities, factors indicative of heart disease (left ventricular hypertrophy, left ventricular dilatation, cardiomyopathy), atrial fibrillation, myocarditis, ischemic heart disease, angina pectoris, a parental history of HF, congenital heart disease, as well extracardiac conditions (renal insufficiency, obstructive pulmonary disease, rheumatic fever, sleep apnea) all increase the risk of HF {57},{82},{58}. There is no doubt on the relation of obesity, increased cholesterol values and hypertension to cardiovascular morbidity and mortality {82}. According to the AHA, seventy-five percent of HF cases have antecedent hypertension {83}.

As regards socio-demographic and clinical factors, the Heart Disease and Stroke Statistics of the AHA reveal various risk factors for HF that have been identified by a range of studies. As such, an increasing age, a male gender, an African American race, hypertension, obesity, a low socio-economic status, a history of atrial fibrillation, and a diagnosis of CHD are socio-demographic risk factors that increase the likelihood for developing HF. Lifestyle risk factors that increase the risk of HF are smoking, an unhealthy diet, high alcohol consumption, a sedentary behavior, and high salt intake {83}. Atherosclerosis is another very important clinical risk factor for the development of HF {115}. Other clinical risk factors associated with incident HF relate, amongst others, to a low level of adiponectin and a high level of pro-B-type natriuretic peptide (BNP) in the bloodstream, a high sodium level in the blood, an increased urinary albumin excretion, an elevated serum γ-glutamyl transferase, higher levels of hematocrit, increased circulating concentrations of resistin, cystatin C, inflammatory markers (interleukin-6 and tumor necrosis factor-α) and low serum albumin levels. Moreover, cardiomyopathy, ventricular premature complexes, left ventricular mass index, cardiac (high-sensitivity) troponin, and changes in high-sensitivity troponin levels have been significantly associated with incident HF {117},{83}. Several of these risk factors do slightly differ between HFPEF and HFREF underscoring differential pathophysiological mechanisms for both subtypes of HF. As such, a higher age, a female gender, cystatin C, increased urinary albumin excretion, and a history of atrial fibrillation have been strongly associated with the new onset of HFPEF. Conversely, a male gender, current smoking, an increased highly sensitive troponin T or an increased pro-B-type natriuretic peptide, and previous myocardial infarction have revealed to significantly increase the likelihood for HFREF {5}.

According to the ESC 2012 {77}, HF with reduced ejection fraction or systolic HF is the best understood type of HF in terms of pathophysiology and treatment. Coronary artery disease is the cause of approximately two-thirds of cases of systolic HF, although hypertension and diabetes are probable contributing factors in many cases. There are many other causes of systolic HF, which include previous recognized or unrecognized viral infection, an increased alcohol intake, chemotherapy, and ‘idiopathic’ dilated cardiomyopathy {77}.

HF with a preserved ejection fraction or diastolic HF seems to have a different epidemiological and etiological profile from HF with a reduced ejection fraction. Patients with diastolic HF are more often older, female have a history of hypertension and are obese compared with those with systolic HF. They are less likely to have coronary heart disease but more likely to have hypertension and atrial fibrillation {77}. Coronary artery disease, diabetes mellitus, and hyperlipidemia are also highly prevalent in HFPEF patients {115}. Patients with diastolic HF have a better prognosis than those with systolic HF {77}.

Many developing countries are facing similar risk factors as developed countries due to a shift towards a Western-type lifestyle. Other risk factors related to infections caused by bacteria and tropical parasites contribute to the development of HF in these countries as well. Infections remain an important cause HF in many developing countries such as rheumatic fever due to preventable bacterial infections. HIV is also an important risk factor for heart-related disease since it leads to increased risk for infections due to a weakened immune system. Although rheumatic HF is the most common cause for HF in certain countries of South Asia, trends towards an ischemic cause for HF have also been observed in Asia, China and Japan {98}. In areas of South America, Chagas, a parasitic infection, is the cause for HF in almost 50 % of all HF cases {73}. In tropical areas, Davies has been a major risk factor for HF {111}. According to the systematic review and pooled analysis by Khatibzadeh et al. 2013 {58}, risk factors of HF vary considerably among six world regions. In their review, crude proportion of HF patients with an ischemic heart disease was highest in Europe and North America, followed by East Asia, Latin American and the Caribbean, and lowest in Sub-Saharan Africa. Hypertension was an important risk factor in all regions, whereas cardiomyopathy was the most common risk factor in Latin America, the Caribbean, Sub-Saharan Africa, and Asia Pacific High Income. Cardio-pulmonary disease was most prevalent in HF patients in East Asia, likely due to the high smoking prevalence. Rheumatic heart disease appeared to be most prevalent in East Asia and Sub-Saharan Africa {58}. These findings are similar to two reviews that revealed a high proportion of HF attributed to ischemic heart disease in developed countries, and a higher proportion of HF attributed to rheumatic heart disease and non-ischemic cardiomyopathies in developing countries {61},{78}.

As regards risk factors for hospitalization in HF, these concern a higher age, a nonwhite race, a low socio-economic status, lack of employment, living alone, smoking, ischemic heart disease, a low systolic blood pressure, a higher NYHA class (III or IV), prior HF hospitalization, the presence of hypertension, diabetes mellitus, anemia, hyponatremia, a history of renal insufficiency, worsening renal function, chronic obstructive pulmonary disease, obstructive sleep apnea, depression, a low quality of life and absence of emotional support or social network, and a low adherence to therapies, to name a few {30}. Risk factors for hospital readmission among older persons with a new onset of HF have also been identified. These concern diabetes mellitus, NYHA class III or IV, chronic kidney disease, a reduced ejection fraction (< 45 %), muscle weakness, slow gait, and having a depression {8}.

Healthy lifestyle factors such as a normal weight, nonsmoking, regular exercise, moderate alcohol intake, a healthy diet (consumption of fruit and vegetables and consumption breakfast cereals) are related to a lower risk of HF. Moreover, high circulating individual and total omega-3 fatty acid concentrations decrease the likelihood for developing HF {83}.

Evidence exists that obesity, an elevated blood cholesterol level and hypertension are associated with a greater survival in HF patients. This phenomenon has been termed “reverse epidemiology” {54}. Although the phenomenon is not yet clearly understood, proposed explanations are the syndrome of cardiac cachexia, reverse causation and time discrepancies among competitive risk factors. The reverse epidemiology does not hold for all conventional risk factors, as smoking cessation improves prognosis in HF patients {105}.

• The basic search for the CUR domain was used to answer this question. No article of the basic search was relevant for this assessment element. Therefore, a manual search was done to find relevant information about the natural course of the health condition as published in evidence-based guidelines on the HF epidemiology. European and American guidelines for the diagnosis and treatment of acute and chronic HF were consulted by doing a manual search on the website of the European Society of Cardiology (ESC) and the American Heart Association (AHA), and the references of the ESC guidelines published in 2008 and 2012 and the AHA practice guideline published in 2013 were reviewed and this led to one additional article that was relevant for this assessment element (Mosterd & Hoes, 2007) {82}. The references from the selected studies for the CUR domain were also reviewed, leading to seven additional relevant references.
• The searches for the guidelines were additionally conducted the 06th of January 2015 by one of the investigators (NB).

In patients with left ventricular systolic dysfunction, the maladaptive changes occurring in the cardiac muscle after myocardial infarction lead to pathological adaptation of the ventricle with dilatation and impaired contractility. This in turn is one measure of a reduced ejection fraction {76}. In the absence of treatment of the systolic dysfunction, these maladaptive changes worse progressively over time, leading to further enlargement of the left ventricle and further decline in the ejection fraction. The patient may yet initially not reveal any particular HF symptoms. Two mechanisms are thought to account for this progression. The first is occurrence of recurrent myocardial infarction leading to additional myocyte death. The other is the systemic responses induced by the decline in systolic function, particularly neurohumoral activation. Two important neurohumoral systems activated in HF are the renin-angiotensin-aldosterone system and sympathetic nervous system. In addition to causing further myocardial injury, these systemic responses have destructive effects on the blood vessels, kidneys, muscles, bone marrow, lungs, and liver. They account for many clinical features of the HF syndrome. Clinically, the maladaptive changes after myocardial infarction account for the development of HF symptoms (pump failure or ventricular arrhythmia) and these worsen over time. The ultimate consequences are a reduced quality of life, a reduced functional capacity, decompensation leading to hospital (re-)admission, and death. The impaired cardiac function also depends on atrial contraction, synchronized contraction of the left ventricle, and a normal interaction between the right and left ventricles. Events affecting any of these or imposing an additional load on the heart (e.g. anemia) can lead to acute decompensation {77}.

The initial cause of HF influences its further prognosis. As such, HF caused by viral myocarditis may lead to complete recovery, while acute myocardial infarction complicated by HF significantly increases the risk of mortality. Comorbidities known to lead to premature death in HF patients include renal dysfunction, depression and anemia. Patients with both HF and chronic renal failure have an extremely poor prognosis {82}.

Not even three decades ago the majority of HF patients died a few years after the diagnosis, and admission to hospital with worsening symptoms was frequent and recurrent. This led to high hospitalization rates for HF in many countries. Effective treatment has reduced hospitalization rates for HF to 30–50 % and has led to small but significant decreases in mortality {104},{53}. Nowadays, the mortality rate reaches approximately 50 % within 5 years of admission among HF patients {19}. Patients with a new onset of HF have a mortality risk varying generally between 20 % and 40 % within the first year after hospital admission for HF {121}, {68},{53},{36}. Between 20 and 30 % patients are readmitted within the first month after hospital discharge and almost 50 % at 6 months. Due to the aging population these percentages are expected to rise  {37},{30}. Hence, life expectancy is considerably reduced in HF patients and acute or slow worsening of HF occurs in most of the patients leading to a (highly) reduced quality of life {82}.

The pattern of readmissions in HF patients has been referred to as the “three-phase terrain” of HF readmissions because epidemiological data revealed that 30 % of readmissions occur during the first two months after hospital discharge, 50 % of readmissions occur within the last two months before death, and the remaining 20 % of readmissions occur in-between {122}.

• The basic search for the CUR domain did not provide any relevant information to answer this assessment element. Hence, a manual search was done to find relevant information about symptoms and burden of disease for the patient at different stages of the HF syndrome as published in evidence-based guidelines on the HF epidemiology. European and American guidelines for the diagnosis and treatment of acute and chronic HF were consulted by doing a manual search on the website of the ESC and the AHA resulting in the following guidelines and references:
• Since the Killip classification describes the severity of a patient’s HF condition in the context of myocardial infarction in different stages and this was mentioned in the ESC guidelines from 2012, two additional studies were consulted on this classification system:
• Furthermore, the website of the ESC was consulted which led to one additional position paper on advanced chronic HF relevant for this assessment element:
• The searches for the additional guidelines were conducted the 06th of January 2015 by one of the investigators (NB).

Burden of disease for different stages of heart failure

According to the ESC guidelines published in 2012 {77}, “a patient who has never exhibited the typical signs or symptoms of HF is described as having asymptomatic left ventricular systolic dysfunction (or whatever the underlying cardiac abnormality is)”. HF generally is a chronic condition and patients who have had HF for some time are often said to have ‘chronic HF’. A treated patient with symptoms and signs that have unchanged for at least a month is said to be ‘stable’.

‘Acute HF’ is the term used to describe the rapid onset of, or change in, HF symptoms and signs. Acute HF is an event with severe symptoms and signs of considerable prognostic importance. Causes of acute HF include arrhythmias, myocardial ischemia, and acute preload or afterload changes. In most cases, acute HF arises as a result of deterioration in patients with chronic stable HF who had a previous diagnosis of HF. Hence, the patient may be described as ‘decompensated’. AHF usually requires admission to hospital and immediate intervention. Acute HF may also be the first presentation of HF (‘de novo’ acute HF). In that case, acute HF may be caused by an abnormality of a cardiac function such as acute myocardial infarction, for example in a patient who has had asymptomatic cardiac dysfunction, often for an indeterminate period, and may persist or resolve. In that case, patients may become ‘compensated’. Patients with pre-existing HF often have a clear trigger, such as an arrhythmia or discontinuation of diuretic therapy in a HF patient with a reduced ejection fraction, and volume overload or severe hypertension in HF patients with a preserved ejection fraction. The acuteness may vary. Patients may experience a period of days or even weeks of deterioration (e.g. increasing breathlessness or edema) whereas others develop HF within a few hours to minutes (e.g. in association with an acute myocardial infarction).

HF symptoms can range from life-threatening pulmonary edema or cardiogenic shock to worsening peripheral edema. Although symptoms and signs may resolve in patients with a new HF, the underlying cardiac dysfunction may not. These patients have an increased risk of recurrent ‘decompensation’. Sometimes, however, a patient may have HF due to a problem that resolves completely (e.g. acute viral myopericarditis). Particularly those patients with ‘idiopathic’ dilated cardiomyopathy may show considerable or complete recovery of left ventricular systolic function with modern treatment including an angiotensinconverting enzyme inhibitor, beta-blocker, and mineralocorticoid receptor antagonist.

‘Congestive HF’ is a term may describe acute or chronic HF with evidence of congestion (i.e. sodium and water retention). Congestion, though not other symptoms of HF (e.g. fatigue), may resolve with diuretic treatment {77}. Many patients may further progress to ‘advanced chronic HF’. The ESC developed a definition of advanced HF with objective criteria that is helpful. According to the ESC, these patients often have severe symptoms (NYHA class III or IV), episodes with clinical signs of fluid retention and/or peripheral hypofusion, objective evidence of severe cardiac dysfunction, severe impairment of physical exercise, history of at least 1 HF hospitalization the previous 6 months, and presence of all the named features besides optimal therapy. These patients generally have a poor prognosis and high risk of events {79}.

‘End-stage HF’ indicates a highly advanced and irreversible stage of HF where conventional HF treatment cannot lead to an improvement. In these patients, palliative care or heart transplantation are indicated. Many or all of these terms may be accurately applied to the same patient at different times, depending upon their stage of illness {77}.

A useful classification of HF based on the nature of clinical representation has been revealed by the ESC guidelines on the diagnosis and treatment of HF:

Table 2. Classification of heart failure

Source: ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure (Dickstein et al., 2008) {19}

New-onset HF refers to the first presentation of HF. Transient HF refers to symptomatic HF over a particular time period, although long-term treatment may be indicated. Examples are patients with mild myocarditis from who almost recover completely, patients with a myocardial infarction who need diuretics in the coronary care unit but who don’t need long-term HF treatment, or transient HF caused by ischemia and resolved by revascularization. Worsening HF in chronic HF (decompensation) is a very common form of HF leading to hospital admission. Treatment should be based on the clinical presentation for which specific therapy is indicated (e.g. pulmonary edema, hypertension emergency, acute MI) {19}.

Classification of heart failure by its symptoms and functional capacity

The severity of the symptoms and limitations of physical activity of HF are usually assessed according to the New York Heart Association (NYHA) functional classification. This classification system has been proven to be clinically useful. Patients in NYHA class I are essentially asymptomatic and have no symptoms attributable to heart disease or are well treated and their symptoms may have relieved. Patients in NYHA class II have mild symptoms of HF and a slight limitation in physical activity; those in class III have moderate symptoms and symptoms while walking on the flat; and those in class IV are said to have severe symptoms while being breathless at rest and essentially housebound  {77},{115}.

It is important to note that symptom severity correlates poorly with underlying cardiac dysfunction. Although there is a clear relationship between severity of symptoms and survival, patients with mild symptoms may still have a relatively high absolute risk of hospital admission and death (McMurray, 2010; Chen et al., 2011; Dunlay et al., 2009) {76},{9},{22}. HF symptoms can also change promptly. As such, a stable patient with mild symptoms can become abruptly breathless at rest with the onset of an arrhythmia, and an acutely unwell patient with pulmonary edema and NYHA class IV symptoms may recover quickly with diuretic treatment. Deterioration in symptoms increase the likelihood of hospital admission and death {77}.

Table 3. New York Heart Association functional classification based on functional capacity

Source: Hunt et al., Circulation 2005;112:e154–e235. {46}

Another classification by the American Heart Association (AHA) and the American College of Cardiology (ACC) describes HF in stages based on structural changes and symptoms as follows:

Table 4. ACC/AHA stages of heart failure

Source: Yancy et al., JACC 2013;16:e148-e231. {115}

The ACCF/AHA stages recognize that risk factors and abnormalities of the heart are associated with HF. The stages are progressive and violate, meaning that once a patient moves to a higher stage, regression to a former HF stage is not possible. The NYHA functional classification rates the severity of symptoms in those with structural heart disease and the stage in which a patient resides can change short time periods. Whereas the ACCF/AHA classification system of HF emphasizes the development and progression of disease and can be used to describe patient, the NYHA classification focuses on exercise capacity and the symptomatic status of the disease {115}.

The Killip classification may be used to describe the severity of a patient’s HF condition in the context of myocardial infarction. In fact, patients are categorized according to the presence or absence of simple physical examination findings that suggest ventricular dysfunction in order to provide a clinical estimate of the severity of acute myocardial infarction {59}. According to this classification system, patients are classified into four levels during physical examination. Patients in Class I demonstrate no evidence of congestive HF due to the absence of clinical signs of cardiac decompensation. Patients in Class II have findings and clinical signs consistent with mild to moderate HF (i.e. lung rales, pulmonary venous hypertension, pulmonary congestion). Patients in Class III demonstrate severe HF by overt pulmonary edema with rales throughout the lung fields. Patients in Class IV are in cardiogenic shock with clinical signs of hypotension and evidence of peripheral vasoconstriction {23}.

Table 5. The Killip classification for the severity of a patient’s HF condition in the context of myocardial infarction

Sources: De Gaere et al., 2001 {17 }; El-Menyar et al., 2010 {23}

Basic search was used for this question and only articles reporting data related to the telemonitoring impact on the burden of disease were selected. No further research was needed. Systematic reviews and most recent article were taken in to account first. No quality assessment tool of articles was used. We just provide the  information relative to structured telephone support. 6 reviews were selected.

Telemonitoring impact on burden of heart failure is measured here as decrease in heart failure related hospitalization, heart failure related length of stay, and all cause mortality.

In short the listed reviews gave the foloowing information:

• There is substantial heterogeneity in the results {33}.

• Telehealth programmes demonstrated clinical effectiveness in patients with CHF compared with usual care {114}.

• It was not clear as to the extent to which these effects were due to tele-monitoring per se or to the improvement in access to care {44}.

• Structured telephone support and telemonitoring are effective in reducing the risk of all-causemortality andCHF-related hospitalisations; in patients with CHF; they improve quality of life, reduce costs, and evidence-based prescribing {48}.

• Home telemonitoring is generally clinically effective, and no patient adverse events were reported in the included studies {93}.

• Telemonitoring appears to be an acceptable method for monitoring of HF patients {75}.

The provided effectiveness data were

For mortality

• Fixed effect model risk ratio 0.76, 95 % CI 0.66 to 0.88 {114} – mortality

• hazard ratio [HR]: 0.97; p=0.87 {102}– mortality

• RR 0.66; 95 % CI 0.54 - 0.81; P < 0.001 {48} for invasive telemonitoring – mortality

• RR 0.88; 95 % CI 0.76 –{48} for structured telephone support– mortality

• risk ratio ¼ 0.64; 95 % CI: 0.48–0.85 {93}– mortality

for CHF related hospitalisation

• Random effect model risk ratio 0.72, 95 % CI 0.61 to 0.85 {114}– hospitalisation

• hazard ratio (HR: 0.89; p=0.44 {102} – hospitalisation

• RR 0.79; 95 % CI 0.67 - 0.94; P = 0.008 {48} for invasive telemonitoring – hospitalisation

• RR 0.77; 95 % CI 0.68- 0.87; P < 0.0001). 1.01; P = 0.08 {48} for structured telephone support– hospitalisation

Gorthy 2014 {33} included in a systematic review 14 RCTs (from January 1975 to August 2014) evaluating the efficacy of non-invasive telemonitoring. 2 out of 12 studies reporting cardiac or all-cause mortality demonstrated a significantly positive effect, 3 out of 13 reported a significant reduction of all-cause hospitalization and 3 out of 10 reported reduction in HF hospitalization. 1 study demonstrated significant improvement of b-type naturetic peptide levels and quality of life using a mobile-phone-based telemonitoring system. 2 studies compared structured telephone support against non-invasive telemonitoring:

• The first (TEN-HMS) randomized 426 patients to usual care (n = 85), structured telephone support (n = 173), or to non-invasive telemonitoring (n = 168)] demonstrated significant reduction in all-cause mortality of both intervention arms compared to usual care with no significant difference in HF/all-cause mortality and hospitalization between the two inteventions.

• The second randomized 160 patients to usual care and 301 patients to one of three intervention groups. Strategy 1 employed structured telephone support alone (n = 104), strategy 2 employed structured telephone support plus weekly transmission of vital signs including changes in weight, blood pressure and symptoms (n = 96), and strategy 3 employed the same intervention used in strategy 2 plus a monthly 24-h cardiorespiratory recording (n = 101). All-cause hospitalization, HF hospitalization, and mortality were not significantly reduced in the more intensive strategy 2 and 3 intervention groups compared to strategy 1 patients. There was no significant effect of Home telemonitoring in reducing bed-days occupancy for HF or cardiac death plus HF hospitalization.

Gorthy et al. report substantial heterogeneity in the results. They mention that telephone or non-invasive telemonitoring have the advantage to reach large numbers of patients in regionally distant areas or are limited in travel. They assume that structured telephone support should be a relatively inexpensive treatment option. Non-invasive requires a certain degree of health-literacy of patients who must interact with the system to provide the information to the healthcare provider. The authors conclude that one approach applied to a broad spectrum of different patient types may not be effective.

Xiang 2013 {114} included in their systematic review 26 studies (of 33) concerning tele-monitoring from 2001-2012 with 7530 patients (15 of the 33 articles were in Gorthy 2004 review) and report within their meta-analysis that telehealth programmes had significant overall effectiveness in reducing all-cause mortality (Fixed effect model risk ratio 0.76, 95 % CI 0.66 to 0.88), CHF-related hospitalization (Random effect model risk ratio 0.72, 95 % CI 0.61 to 0.85) and CHF-related length of stay (Random effect model mean difference 21.41 days, 95 % CI 22.43 to 20.39). In addition, telehealth programmes showed significantly greater effectiveness in reducing mortality and hospitalizations among patients with higher New York Heart Association (NYHA) categories. The authors conclude that telehealth programmes demonstrated clinical effectiveness in patients with CHF compared with usual care.

A NICE 2010 Guidance {44} included 8 RCTs on telemonitoring from 2003-2010 (5 of these double with  in above listed articles). They report that the trials reviewed showed an improvement in all-cause mortality and all cause-hospitalisation rates when tele-monitoring, with intensive reviews and contact with the specialist team, was compared to standard care. The authors discuss that it was not clear as to the extent to which these effects were due to tele-monitoring per se or to the improvement in access to care by the patients assigned to tele-monitoring and no recommendation was made.

Inglis 2010 {48}, a Cochrane Review, included 27 controlled studies (from January 1966 to 6 May 2006) of which 11 used non-invasive telemonitoring (2,710 patients) and 16 used structured telephone support (5,613 patients) into a meta-analysis. The authors report an all-cause mortality significantly reduced by non-invasive telemonitoring (RR 0.66; 95 % CI 0.54 - 0.81; P < 0.001) but not by structured telephone support (RR 0.88; 95 % CI 0.76 – 1.01, P = 0.08). HF hospitalizations were significantly reduced by both telemonitoring (RR 0.79; 95 % CI 0.67 - 0.94; P = 0.008) and structured telephone support (RR 0.77; 95 % CI 0.68- 0.87; P < 0.0001). 1.01; P = 0.08). The authors conclude that structured telephone support and telemonitoring are effective in reducing the risk of all-causemortality and CHF-related hospitalisationsin patients with CHF; the interventions improve quality of life, reduce costs, and evidence-based prescribing.

Polisena 2010 {93} included 21 studies from 1998-2008 with 3082 patients in a systematic review and report that home telemonitoring reduced mortality (risk ratio ¼ 0.64; 95 % CI: 0.48–0.85) compared with usual care. Several studies suggested that home telemonitoring also helped to lower the number of hospitalizations and the use of other health services. Patient quality of life and satisfaction with home telemonitoring were similar or better than with usual care. The authors conclude that their review demonstrated that home telemonitoring is generally clinically effective, and no patient adverse events were reported in the included studies. More studies of higher methodological quality are required to give more precise information about the potential clinical effectiveness of home telehealth interventions.

Maric 2009 {75} included 56 articles on telemonitoring from before 2007 into a systematic review. The authors report that most studies demonstrated improvements in outcome measures, including improved quality of life and decreased hospitalizations. However, not all studies reported the same improvements and in several cases the sample sizes were relatively small. The authors conclude that telemonitoring appears to be an acceptable method for monitoring of HF patients. Controlled, randomized studies directly comparing different modalities and evaluating their success and feasibility when used as part of routine clinical care, are now required.

Basis search was not sufficient and a search (mainly on Medline) of all available guidelines in English was done. No quality assessment of guidelines was done. Focus was made on telemonitoring indications within the reviewed guidelines. Three additional studies were included during the consultation phase.

There is interest in new approaches of telemonitoring {1}, but at the moment there is no guideline recommendation available (possible) {45,24,1,110,3,33,44} for telemonitoring in general but for multidisciplinary CHF management programmes {87}.

Following is a brief description of how telemonitoring is included in available guidelines:

The Global heart failure Awareness Programme (Heart failure: preventing disease and death worldwide.  http://www.escardio.org/communities/HFA/Documents/WHFA-whitepaper-15-May-14.pdf?hot=highlighton) {45} includes telemonitoring devices among the new approaches to long-term management outside hospital and encourage more research on these approaches before recommending for they are promising but yet failing to provide clear improval of survival.

The ESC guideline {77} states that for telemonitoring with implantable devices, a guideline recommendation is not yet possible and reports two studies, one about thoracic impedence monitoring which has not yet shown to improve {110} and another one that measures pulmonary artery preassure which did reduce hospital admission for HF in one RCT {1}. Nevertheless, more recent studies have revealed that automatic implant-based multiparameter telemonitoring devices are likely to improve clinical outcomes in patients with chronic heart failure (Hindriks et al., 2014; Parthiban et al., 2015). {125} {126} Relatively to remote monitoring without implantable devices to date they have given inconsistent results and not yet support a guideline recommendation {3}.

Other diagnostic factors, such as asymptomatic atrial fibrillation, patient activity, mean resting heart rate, right ventricular pacing percentage, and cardiac resynchronization therapy pacing percentage, might help. Combined heart failure device diagnostics have been demonstrated to improve the identification of patients at a higher risk of subsequent heart failure hospitalizations. Recently, the Implant-based Multiparameter Telemonitoring of Patients with Heart Failure randomized clinical trial demonstrated that daily automatic remote monitoring enabled early action to be taken in response to the warning signs of acute decompensated heart failure (not including thoracic impedance), resulting in lower all-cause mortality and hospital admission rates for heart failure (Slotwiner et al., 2015).

A recent consensus paper recommends all patients with a cardiac implantable electric device should be offered remote monitoring as part of the standard follow-up management strategy.  This implies that all patients with a cardiac implantable electric device will have the recommendation to be followed with remote monitoring, with the possibility of easy implementation of remote monitoring or telemonitoring with telephone support also for heart failure. (Slotwiner et al., 2015).{127}

Pulmonary artery pressure monitoring using a wireless, passive, radiofrequency sensor implanted into a distal branch of the descending pulmonary artery was approved by FDA for implant in NYHA class III HF patients who have been hospitalized for HF in the previous year {33}.

NICE chronic heart failure guidilens {44} given the difficulties of interpretation of the evidence, the GDG did not make specific recommendations for home telemonitoring but agreed that a research recommendation should be made.

The Australian guidelines (National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand) {87} state that all patients hospitalised for heart failure should have post-discharge access to best-practice multidisciplinary chronic HF care that is linked with health services, delivered in acute and subacute healthcare settings and that priority should be given to face-to-face management while the application of remote management assisted by structured telephone support and telemonitoring should be considered for those patients who do not have ready access to a chronic HF management programme (Grade A recommendation).

Basis search was not sufficient and a search (mainly on Medline) of all available guidelines in English was done. No quality assessment of guidelines was done. Focus was made on diagnosis indications within the reviewed guidelines.

Most guidelines agree on three essential stages of care for patients with heart failure:

-Diagnosis (should be timely and accurate);

-Treatment (should be appropriate to each patient and available urgently if necessary);

-Longterm management (should include follow-up, monitoring and support).

Disagreement is observed on which diagnostic tools should be used for all patients with suspected heart failure and in which order.

Especially for invasive diagnostics there are some differences and challenges according to the interpretation of the diagnostic and prognostic value {45}

The Global heart failure Awareness Programme {45} reported that many guidelines have been published [North America (Canada: CCS and USA: ACCF/AHA, HFSA), Europe (England and Wales: NICE, France: HAS, Germany: DEGAM, Scotland: SIGN) and Aia (Japan: JSC, Singapore: MoH) for heart failure patients and although they may differ in what evidence is included and how it is assessed and in what is considered appropriate, the all agree on three essential stages of care for patients with heart failure: diagnosis (should be timely and accurate)-treatment (should be appropriate to each patient and available urgently if necessary)-longterm management (should include follow-up, monitoring and support. They state that an international consensus recommendation leading to greater clarity about best practice with endorsement from credible local bodies would be of help. Although published guidelines agree on which diagnostic tools are useful, they disagree on which should be used for all patients with suspected heart failure and in which order. Making an accurate diagnosis requires a range of diagnostic tools, in conjunction with clinical judgement and expert knowledge.

The ESC guidelines {77} highlight particular challenges related to diagnosis of HF-PEF (heart failure with ‘preserved’ ejection fraction) remains a particular challenge, and the optimum approach incorporating symptoms, signs, imaging, biomarkers, and other investigations is uncertain. The following questions are posed: Strain/speckle imaging—value in diagnostic and prognostic assessment of both HF-REF (heart failure with reduced ejection fraction) and HF-PEF? Diastolic stress test—value in diagnosis of HF-PEF?

A recent Australian consensus statement {88} recognizes that many individuals are not diagnosed in a timely manner, and once a diagnosis is made, treatment is frequently sub-optimal.

Basis search was not sufficient and a search (mainly on Medline) of all available guidelines in English was done. No quality assessment of guidelines was done. Focus was made on management indications within the reviewed guidelines.

The Global heart failure Awareness Programme {45} reports that despite clear recommendations regarding evidence-based medications, many patients with heart failure do not receive a prescription for potentially beneficial medication because they do not always comply with guidelines.

In the US more than a quarter of patients with heart failure did not receive an appropriate prescription and in Europe doses are often below those recommended {26},{28},{65}.

In Europe guidelines incorporate follow-up, monitoring  and support however about a quarter (7/26) of the countries reported having heart failure management programmes in more than 30 % ot their hospitals {49} and even when in place, they are not always used. In the US most hospital had fewer than half of 10 key recommended practices in place and fewer than 3 % had 10 in place {4}.

A recent Australian consensus statement {88} report that the management of chronic heart failure remains a pressing problem, with many apparent indicators of poor case detection, including discordant management with evidencebased treatment, recurrent hospital admission, and disconnected care issues these that are amplified among marginalised populations.

Tele-monitoring can be considered on add-on for the existing management options.

Global assessment

-Despite clear recommendations regarding evidence-based medications, many patients with heart failure do not receive a prescription for potentially beneficial medication because they do not always comply with guidelines {45}.

Europe

-In Europe prescription doses are often below those recommended {26},{28},{65};

-In Europe guidelines incorporate follow-up, monitoring  and support, however, about a quarter (7/26) of the countries reported having heart failure management programmes in more than 30 % ot their hospitals {49}  and even when in place, they are not always used.

USA

-In the US most hospital had fewer than half of 10 key recommended practices in place and fewer than 3 % had 10 in place {4};

-In the US more than a quarter of patients with heart failure did not receive an appropriate prescription {26},{28},{65}.

Australia

• A recent Australian consensus statement {88} report that the management of chronic heart failure remains a pressing problem, with many apparent indicators of poor case detection, including discordant management with evidencebased treatment, recurrent hospital admission, and disconnected care issues these that are amplified among marginalised populations.

The listed devices in the included studies were searched for their CE status using google and the device-specific websites.

European Commission at http://ec.europa.eu/growth/index_en.htm

The database for medical devices within the EU (http://ec.europa.eu/health/medical-devices/market-surveillance-vigilance/eudamed/index_en.htm) is access-restricted. And could not be consulted

Italy has a comprehensive national database for medical devices which is in Italian and is accessed only by authorized operators. An open access classification of medical devices in Italian language only (http://www.salute.gov.it/imgs/C_17_pubblicazioni_1687_allegato.pdf) is needed for the research in the database itself, so no results can be provided.

There is also a medical devices registration database for medical devices in Austria, but the access is closed. (http://www.medizinprodukteregister.at/de/start).

An Austrian expert was asked for information.

For equipment used within structured telephone support in a (community-)setting and/or within a disease management programme the devices seem to be individually created for the local need and based on a software for data-collection via App, internet or as a database where data are written in while telephone interviews.

Different related devices like mobile phone applications, bluetooth adaptations (sending data from the scale or bloodpressure device, etc., via telephone to the healthcare center), are used within structured telephone support.

Usually a telephone does not need to be registered as a healthcare device, but any related medical device as regulated within the European Commission at http://ec.europa.eu/growth/index_en.htm

The information from the expert consultation in Austria lead to two homepage information-links which give information about the status of authorisation, another two systems were not found. It is not known whether these systems are used elsewhere than in Austria:

-The AIT Telemonitoringsystem of the Medical University of Graz provides a DMP monitoring device named TMScardio which is used in hospitals and a healtnetwork in Tyrol. There is some official information at http://www.meduni-graz.at/cms.php?pageName=301&year=2013&newsId=25852 (last check on 2.7.2015) and on http://www.ait.ac.at/research-services/research-services-digital-safety-security/health-information-systems/telemonitoring-and-therapy-management/heart-failure/?L=1 (last check 6.7.2015), but not about CE registration (needed ?).

-ELICARD Heart Telemonitoring System, DMP monitoring system, which uses the TMScardio. Information is avaliable at http://bmg.gv.at/cms/home/attachments/4/5/9/CH1417/CMS1423479059781/9_ait_factsheet_telemonitoring_herzinsuffizienz.pdf (last check 6.7.2015), includes the same technical product AIT as mentioned above, we did not find any information about CE mark.

-Two further systems were mentioned, a telerehabilitation discharge-home training-monitoring and a bloodpressure SMS, but with no further information and no hint to a CE mark.

No valid method found. Theoretically every single health system (parts of Europe also with different federal situations) could be studied in details or a survey could be conducted. To get this information one has to clearly know where to look for, and whom to ask (there are maybe more than one organisations to consult for different settings).

We did not provide a survey due to time restriction of this HTA report. A valid selection of experts who know about the reimbursement details in each country or health system, the creation of a questionnaire including all relevant details about settings of STS and potential correlated services, and reduced to patients with chronic heart failure (where the definition within the studies varies) would be a separate project and exceed the ressources of this HTA.

The research on European statistical databases did not result in any information about reimbursemnet (Eurostat, OECD).

The resarch among different Eurpoean websites from healthsystems or related organisations is limited by language and if not, it often does not provide clear information about reimbursement.

No information in the included studies found.

This question is left un-answered. Due to the situation of high complexity among the use and settings within the terminus of „telemonitoring/ telemedicine“and the new or developmental status of the intervention(s) no explicit answer can be provided within this HTA.

Due to the situation of high complexity among the use and settings within the terminus of „telemonitoring/ telemedicine“ and the new or developmental status oft he intervention(s) no explicit answer can be provided.

 In Europe disease management programmes are used and reimbursed in national or regional level or within project level. Whether and how they include telemonitoring and what is reimbursed or and by whom exceeds the time-frame of this review.

It is not clear how to define „reimbursement“:

-As the payment (or reimbursement within benefit baskets/ lump sum payment, etc.) of the carers time/ effort;

-As the payment (or reimbursement within benefit baskets/ lump sum payment, etc.) of the infrastructure (computer, telephone, database, software, etc.);

-As the payment (or reimbursement within benefit baskets/ lump sum payment, etc.) of the usual care and additional telehealthcare;

-As the payment (or reimbursement within benefit baskets/ lump sum payment, etc.) of only the additional telehealthcare;

-As the payment (or reimbursement within benefit baskets/ lump sum payment, etc.) of devices;

-As the payment (or reimbursement within benefit baskets/ lump sum payment, etc.) for the data-collection and evaluation.