Heart failure (HF) is a non-communicable cardiovascular disease defined as a clinical syndrome that affects the heart's ability to meet the body's metabolic demands.^1-3 The inability to pump blood properly results from structural or functional abnormalities that affect the reception or ejection of blood through the heart chambers.^1,4,5 The most frequent causes of HF are ventricular hypertrophy or thickening of the walls of the ventricles caused by acute myocardial infarction, coronary heart disease or hypertension.⁴

HF can be chronic when the patient has had the condition for some time without changes in symptomatology during the last month or acute when the HF has a rapid onset or there is a worsening of the disease. Chronic HF can be stable or decompensated and is more common in older adults; acute HF usually begins as a result of sudden events such as chronic HF decompensation, acute myocardial or right ventricular infarction, hypertensive crises, or acute arrhythmia.^3,6

The main symptoms derive from the decrease in the supply of oxygen to the tissues and the compensatory mechanisms of the organism before the reduction of cardiac flow, which tend to increase intravascular pressures and cause symptoms of congestion. The characteristic HF symptomatology includes^7-10:

1. Dyspnea or "feeling short of breath"
2. Fatigue
3. Ankle swelling
4. Edema
5. Elevated jugular venous pressure
6. Hepatojugular reflux
7. Angor or "oppressive chest pain"
8. Rales or "snapping breath sounds"

The most used classifications to name HF progression or severity of HF are the ACC/AHA (American College of Cardiology/American Heart Association), based on structural damage and symptomatology, and the NYHA (New York Heart Association), focused on the patient's functional ability. The most appropriate treatment for the patient is assigned according to the progression stage.^8,11,12

In the search to address the growing prevalence of HF around the world, diverse groups have worked on identifying risk factors associated with the development of this pathology. Such conditions are closely related to the clinical causes that trigger structural abnormalities of the heart, including the most common diabetes, high blood pressure, obesity, alcohol consumption, smoking, and having a previous heart attack.¹³

As mentioned above, HF is a non-communicable disease whose incidence has increased worldwide. Compared to past decades, non-communicable diseases are currently responsible for most of the deaths in the world as a result of the rise in the prevalence of their etiological causes and risk factors, while infectious diseases show a downward trend, both in prevalence and in causes of mortality.¹⁴

It is estimated that there are more than 64 million individuals around the world living with HF. The global prevalence ranges from 1% to 2% depending, mostly, on the income or industrialization of each country.^5,15-17

The annual prevalence rate in the Mexican population is 2.1% in men and 1.9% in women, showing an incremental relationship with the age group. According to the Ministry of Health, 4% of the adult population and more than 20% of the population over 65 years suffer from this disease.^18,19

The frequency of hospitalization also increases with age. In the age group of 65 to 69 years, the proportion of patients with HF requiring hospitalization is 8%, while in the 85 to 89 years group is 13%. According to data from Latin America, the average stay hospitalization is 6 days with a range of between 5 and 11 days. HF in-hospital mortality in the middle- and low-income countries ranges from 6% to 10%.^4,20-22

Generally, a patient with HF has a bad prognosis due to 50% of those who suffer from it will die 5 years after clinical diagnosis. Annual mortality for patients with diastolic HF is close to 5-8%, while mortality from systolic dysfunction ranges from 10-15%. Mortality in patients with diastolic dysfunction is related to the underlying disease.^23,24

Social and Economic Burden of HF

The life of a patient diagnosed with HF is seriously affected in the short and medium term by the financial expenses derived from the disease. The symptoms that may alter the performance of daily tasks of the patient and the development of side effects that can lead to disability or premature death. Among the main factors associated with the decrease in quality of life of patients with HF are functional limitation, deterioration of the performance of daily activities, the development of frailty, mental health, and cognitive ability.^{1,2,4,17,25,26}

It is noteworthy to mention that among the most critical effects on the mental health of patients with HF is the perception of financial security, derived mainly from job instability caused by periods of disability, in addition to those associated with the treatment of HF and comorbidities.^4,17

Studies conducted on the United States population estimate that the average annual absenteeism in patients with stage NYHA I/II HF is 3.04 days, and 12.66 days for patients with stage NYHA III/IV HF.⁶

In 2017 in Mexico, it was estimated that the years lived with disability (YLD) by HF were 107.62 per 100,000 inhabitants, standing for 1.13% of the YLD nationwide.⁵

In 2015, the costs for the health system by HF in Mexico reached $ 7,556 million pesos and productivity losses of $ 19,457 million; thus, HF was the second disease with the highest financial expenditure with MXN 27,000 million. It is estimated that HF, along with hypertension, atrial fibrillation, and myocardial infarction reach 4% of health expenditure.⁶

Due to the substantial number of people affected by this disease and the importance of being one of the most spending diseases nationwide, there is a need to carry out research on that disease, such as the economic cost of the affected individuals, in addition to the costs generated in the public health system.

The relevance of addressing and prioritizing the study of HF in Mexico is crucial for the public health institutions because that may indicate guidelines for the prevention and timely care of HF and the diseases that derive from it.

This study aims to evaluate the economic impact of HF disease in Mexico through national and international sources. It will be presented a disease burden model in the Mexican context, where the main direct and indirect costs associated with the disease are estimated, along with the consequences on patient's quality of life.

In this study, an economic analysis of the burden of HF in Mexico was conducted using a model that studies the natural progression of the disease. The model used consists of a Markov chain simulating the progression of the disease and the associated expenses in a patient during 16 years of evolution. The results were projected to estimate the burden of HF in the health system in Mexico; economic expenses and disability-adjusted life years (DALY) were used as burden parameters.

The proposed Markov model considered four health stages corresponding to the NYHA classification (Figure 1).²⁷ Two possible final health states were included: death from any cause and death from HF.

The beginning of the model contemplates a hypothetical 60-year-old patient who can live up to 75 according to life expectancy in Mexico. Therefore, model transitions were considered over 16 years, with 6-month analysis cycles consistent with the evaluation period in the study reporting transition probabilities.^13,28,29

The initial distribution of patients throughout the 4 NYHA stages of HF (I: 38%, II:34%, III:23%, and IV:5%) as well as the probabilities of transition between states at six months (Table 1) were considered from the literature and based on the population projections of Mexico.^28-30

The average mortality of people aged 60 was calculated regarding the probability of death from any cause. Since CONAPO data are annual and the analysis cycles are six months, the mortality rate was adjusted for a semi-annual temporality.^28-30

Estimation of the Economic Burden of HF

The model estimates direct and indirect costs associated with the disease and the calculation of the impact on quality of life. For direct costs, expenses associated with diagnosis, pharmacological treatment, hospitalization, and consultations with the specialist according to the stage of HF were considered.

It is worth mentioning that a panel of experts from Instituto Nacional de Cardiología (National Institute of Cardiology) —a public health institution belonging to the Ministry of Health of Mexico— estimated the costs associated with the diagnosis because no robust information was found in the literature for this area. Detailed information is given in the Appendix.^13,29-32

Regarding indirect costs, productivity loss was assessed and measured monetarily in relation to absenteeism and premature death.²⁷

The cost of absenteeism was calculated with the following formula:

Absenteeism=days of absenteeism x daily salary x EAP x (1-% unemployment)

Where:

• The economically active population (EAP) and the unemployment rate were included according to what Instituto Nacional de Estadística y Geografía (INEGI) reported for the age groups of 60 to 64 years, and over 65.³³

• Days of absenteeism were included based on average annual absenteeism for patients in stage NYHA I/II (3.04 days per year, 1.52 days per semester) and stage NYHA III/IV (12.66 days per year, 6.33 days per semester).⁶
• The basic salary was considered according to the daily average reported by INEGI in 2015 (MXN 363.53).^34,35

Additionally, the proportion of formal employment in Mexico was considered for the cost of absenteeism, which corresponds to 56.20%; as well as the percentage of salary paid by the health institution to estimate the cost for the worker and the government (40% and 60%, respectively, Ley Federal del Trabajo [Federal Labor Act].³³ Finally, the cost of premature death was estimated with the following formula:

Cost of premature death = years of life lost x EAP x (1-% unemployment)

Where:

• Like in the cost estimate for absenteeism, the EAP and the unemployment rate were included according to the INEGI report for the 60-to-64- year group³⁶ and over 65.
• The years of life lost were calculated by subtracting from 75, the age at which death occurs in the model simulations.

Estimation of the Burden on Quality of Life by HF

To estimate the impact of HF on the patient's quality of life, DALYs were calculated by adding the years of life lost due to premature mortality (YLL) and the years of healthy life lost due to disability (YLD).

The methodology for the development of these concepts was based on what was established and recommended by the World Health Organization (WHO) and what was reported by existing studies.^6,37

For YLDs, the following calculation was performed³⁷:

YLDs= prevalent cases x disability weight

On the other hand, the years of life lost due to premature mortality (YLL) were estimated by:

YLLs= number of deaths for the age considered x life expectancy at the age of death

Where:

• The number of deaths and the prevalent cases were obtained based on the model's calculations, an assessment based on an average patient.
• Life expectancy for each specific age was considered from the WHO life tables.³⁷
• The disability weighting was obtained from the estimates of the Institute for Health Metrics and Evaluation (IHME) due to the lack of HF disability weights in Mexico (Table 2).³⁸

Discount Rate

The discount rate for this model is 5% throughout the entire analysis, applying both in costs and results.

5-year HF Burden Analysis

To perform a sensitivity analysis of the model and quantification of disease burden in the medium term, an study was done where the patient's time horizon was 5 years.

HE Direct and Indirect Costs in the Medium and Long-term

The estimation model of direct and indirect costs of HF considered an average patient over 16 years of life, contemplating from 60 years old to 75 (Table 3).

According to the model, the total direct costs for an average patient over the 16 years are MXN 609,112, with the highest percentage of expenses corresponding to hospitalization costs.

On the one hand, the cumulative cost of the studies needed for the diagnosis resulted in MXN 9,821. On the other, indirect costs correspond to MXN 292,443, where 99.6% is due to the cost of premature death.

In the case of absenteeism, the government paid most of the cost per patient since it covers 60% of the salary of the disabled worker. However, there is also a partial loss of income for the employee suffering from HF due to absenteeism.

For the 5-year cost estimate, direct costs are lower than indirect ones, unlike the 16-year scenario where direct costs exceed indirect costs. Costs of absenteeism and premature death are equal to zero after retirement (65 years old in Mexico); thus, patients stop accumulating indirect costs from year 7 of the analysis in the base case scenario. Furthermore, since costs are associated with a discount rate, when considering a 5-year horizon, the discounted cumulative indirect costs are greater than 16 years.

The results are consistent with what was reported by a cost analysis by HF in 197 countries, where it is found that direct costs represent about 60% and indirect costs 40%.³⁹

Finally, to estimate the projected direct and indirect costs to the Mexican population with HF, the HF prevalence reported (1.38%) in the ENSANUT was used. Considering that the adult population in Mexico is 88,155,630 people, the total number of individuals living with this disease is 1,216,548. Therefore, in Mexico, HF's estimated annual total cost amounts to MXN 103,648,506,213, where about 55% is represented by direct costs, while approximately 45% corresponds to indirect costs (Table 4).

Estimation of the Impact on Quality of Life by HF

Besides the HF economic implications, the impact on the quality of life of an HF patient was assessed: DALYs were calculated as described in the methodology, composed of the YLLs and the YLDs. With an estimated time of 16 years, the resulting YLLs and YLDs for an average patient were 9.61 and 0.91, respectively. Adding the previous values, the DALYs were obtained; 94% of DALYs correspond to the years of life lost due to premature death (Table 5).

After reviewing the literature and according to the results of the disease burden model, there are different gaps in the care, prevention, monitoring and scientific research for HF. There is scarce up-to-date national evidence about pharmacological treatment and aspects related to the number of resources used by each patient depending on the severity of the disease. Thus, there is a need to conduct clinical research that evaluates the specific Mexican population in the national context.

Concerning the quality of life and the scarce national information, it was found that there were no disability weights for the Mexican case at the time of the study. That emphasizes the need for the study of this aspect in the Mexican population.

Regarding the issue of quality of life, there is limited information on patients' cognitive and mental health. In addition, some authors point out a more significant number of unmet needs in the psychological and social domains since these figures are less studied than the physical and functional aspects. That highlights the lack of personalized research based on the different characteristics of the patient (stage, risk factors,comorbidities and socioeconomic background).⁴⁰

In the disease burden model, the costs generated by HF fall both on the patient suffering from the disease and on public health institutions. However, since the proportion of informal employment is higher than that of formal jobs, the expenses for loss of productivity could fall, to a greater extent, on the population and not on the government.

Therefore, it should be underlined that the Mexican population faces disadvantageous health financing factors derived from the insurance scheme and the predominance of informal employment. We must be aware that, in Mexico, 58% of total health spending corresponds to out-of-pocket spending, which comes from the income of individuals, so, in many cases, the lack of financial protection in health generates catastrophic expenses for families. Consequently, the importance of the socioeconomic factors associated with HF should be highlighted since, in general, individuals with higher incomes have a higher net expenditure on health. That represents a lower proportion of their income than individuals with lower income, emphasizing the unmet needs in the population with economic disadvantages.⁴¹

Due to the epidemiological transition, the economic burden of cardiovascular diseases is one of the conditions that entail a higher cost for public health institutions.¹⁴

Indeed, the prevention and evolution of chronic diseases, such as HF, are influenced by multiple socioeconomic factors. Therefore, despite different prevention programs and attention to risk factors, comorbidities, and diseases that lead to HF development, the control of this pathology has been inefficient. Some of the factors that influence the ineffectiveness of the programs include:

• The inability of the public health system to supply the population either preventive health services, diagnoses, or treatment, and avoid lenghty waiting times, which can be 2.3 to 3 times longer than in private institutions.⁴²
• Influence of socioeconomic factors on the management of HF. It has been found that the level of income is a predictor of the prognosis of HF, so prevention should focus not only on the clinical part but also on the understanding that social and economic variables impact the development of the condition of interest.⁴³

Hence, HF is a multifactorial disease that entails costs for public health institutions and individuals who suffer from it and their families. Likewise, there is a lack of programs with a generalized scope for the least benefited population and a failure to prioritize prevention and awareness of the people at risk.^40,44