Real-World Clinical Burden of Newly Diagnosed Heart failure in Thai Patients

This retrospective cohort study was conducted between 2018 and 2019 across five hospitals in Thailand (i.e., Lampang, Chonburi, Udonthani, Bhumibol Adulyadej, and Queen Sirikit Heart Center of the Northeast, Khon Kaen University). These hospitals were chosen based on their diverse geographic locations and varying service levels including three advanced-level hospitals in the upcountry in the Ministry of Public Health (Lampang, Chonburi, and Udonthani; hospital size is 800, 850, and 300 beds, respectively), one medical school hospital in the upcountry (Queen Sirikit Heart Center of the Northeast; hospital size is 200 beds), and one military hospital in the center (Bhumibol Adulyadej; hospital size is 694 beds). The study's participants were adult patients with the diagnosis of HF.

The participants in this study consisted of adult patients who had received a new diagnosis of HF between January and December 2018. These individuals were identified using International Classification of Diseases (ICD)-10 codes “I50” (representing all cases of HF) and “I50.1” (indicating left ventricular HF) from the databases of the study's hospitals. Patients had to meet the following criteria: (1) newly diagnosed with HF, (2) aged between 18 and 99 years, and (3) had at least two hospital visits between 2018 and 2019. All participants were followed up until December 2019.

This study was conducted in accordance with the principles of the Declaration of Helsinki. The study’s protocol was approved by the Central Research Ethics Committee (CREC) (COA-CREC029/2022) and the local Institutional Review Board (IRB) of each participating institution (see supplementary material). Due to the study's retrospective nature, informed consent was exempted by the IRB.

The data collected in this study were categorized into three main parts as follows:

The etiology of HF was classified into two primary types: (1) coronary artery disease and (2) cardiovascular abnormalities stemming from conditions such as hypertensive heart disease, dilated cardiomyopathy, hypertrophic cardiomyopathy, valvular heart disease, tachycardia-induced cardiomyopathy, and myocarditis. Medication history involved the medications administered to the participants for treatment of cardiovascular disease or diabetes mellitus before their enrollment in the study. This included medications such as ACEI or ARB, beta-blockers, MRA, diuretics, calcium channel blockers (CCBs), and antidiabetic drugs. Sodium glucose co-transporter subtype 2 (SGLT2) inhibitors data was not collected since the Heart Failure Council of Thailand (HFCT) 2019 Heart Failure Guidelines, which this research followed, did not include SGLT-2 inhibitors.

Demographic data, co-morbidities, the underlying causes of HF, and details about the NYHA functional class and LVEF (which includes results of 2D echocardiogram, where available) were all extracted from the medical records by the research physicians. At the same time, the medication history was retrieved directly from the hospital's database.

The main objective of this study was to assess the prognosis and disease journey of newly diagnosed patients with HF. The primary outcomes included their likelihood of hospitalization, rehospitalization, unscheduled hospital visits related to HF, as well as all-cause mortality and cardiovascular (CV) mortality.

Unscheduled hospital visits were defined as unplanned visits to either the outpatient department (OPD) or the emergency department (ED). Hospitalization was identified as an admission to an acute care facility for HF, which could include admissions in hospital wards, intensive care units (ICU), coronary care units (CCU), and cardiac intensive care units (ICCU). Rehospitalization was defined as an inpatient admission to an acute care facility for HF within specific timeframes: 30 days, 60 days, 180 days, and 1 year following discharge from a prior hospitalization. All-cause mortality was defined as any death due to any cause, whereas CV mortality specifically referred to deaths related to cardiovascular events. The outcomes were verified among the participants by accessing data from the hospital databases.

The secondary outcome was the quality of care for newly diagnosed patients with HF. Quality of care was measured by the proportion of newly diagnosed patients with HF successfully enrolled in an HF clinic. Additionally, we evaluated the extent to which these patients received guideline-directed medical therapy (GDMT). Furthermore, we investigated the proportion of patients with HF reduced ejection fraction (HFrEF) who achieved the recommended target dosage for each component of GDMT, as per the 2019 Heart Failure Guideline of the Heart Failure Council of Thailand (HFCT). The GDMT, as outlined in the guideline, comprises medications such as ACEI, ARB, angiotensin receptor neprilysin inhibitor (ARNI), beta-blockers, and MRA.

Continuous data were reported using two different methods based on data distribution. When the data followed a normal distribution, the data were presented as the mean and standard deviation (SD). In cases where the data did not exhibit a normal distribution, the median and range were applied instead. Categorical data were presented in terms of frequency and percentage (%).

Calculating the hospitalization rate for heart failure, the number of hospitalizations was divided by the total count of newly diagnosed patients with HF. The rehospitalization rates were calculated at four different time points: 30 days, 60 days, 180 days, and 1 year. These rates were determined by dividing the number of patients with HF rehospitalized for all causes and CV-related causes at these specific time intervals by the total number of newly diagnosed patients with HF. The rate of unscheduled visits was estimated by dividing the number of ED visits or unplanned hospital visits at the OPD by the total number of newly diagnosed patients with HF.

All-cause mortality and CV mortality rates were estimated by dividing the number of deaths attributed to all causes and CV-related causes by the total number of newly diagnosed patients, respectively. To provide a measure of confidence in our findings, we estimated 95% confidence intervals (CI) for all proportions and rates. All data analyses were carried out using SAS program version 9.4.

The quality of care of our participants is presented in Table 2. Most patients with HF were categorized as NYHA class II (62.2%). In comparison, roughly 35.0% of all HF types were categorized as NYHA class III or IV, but only 3.1, 5.0, and 6.6% of HFrEF, HFmrEF, and HFpEF patients were classified as NYHA class I. However, 3.2% of patients with HF were enrolled and treated at a specialized HF clinic. The proportion of patients treated at the HF clinic was highest for HFrEF (5.9%), followed by HFmrEF and HFpEF patients (1.7 and 1.0%, respectively). The median duration from diagnosis to first enrollment in HF care for all patients was 30 days, ranging from 1 to 640 days. Only 64.8% of patients underwent echocardiography and had LVEF data. Among these patients, the mean LVEF was 45.3%.

Regarding GDMT, 42.9, 20.6, 19.0, and 16.2% of patients with HF were given beta-blockers, ACEIs, MRAs, and ARBs, respectively. Only 1.0% received ARNI, mostly among HFrEF patients. Even among patients with HF who achieved the target dose of GDMTs, most fell short of the target doses for all GDMTs. ACEIs (14.1%) and MRAs (13.3%) had the greatest proportion of patients attaining the targeted dose. Furthermore, 5.9 and 1.3% of patients with HF received the recommended dose of beta-blockers and ARBs, respectively. With ARNI, no patients attained the targeted dose.

This is the first study in Thailand to examine the disease characteristics and outcomes in patients newly diagnosed with HF. Additionally, our research collected data from five hospitals across various regions of Thailand. This comprehensive coverage allows for the generalizability of our findings to other newly diagnosed patients with HF in Thailand who receive care at hospitals of a similar standard. In addition, beyond the assessment of disease outcomes, our study evaluated the quality of care provided to newly diagnosed patients with HF. This important information raises awareness of the inadequacies in HF treatment in Thailand and is a valuable resource for healthcare professionals and policymakers. These insights can enhance care quality, ultimately reducing morbidity and mortality among patients with heart failure.

Nonetheless, it is essential to acknowledge certain limitations within our study. Firstly, the hospitals included in our research primarily comprised regional and university hospitals, potentially introducing a referral bias. Consequently, our study participants may have presented more severe disease profiles compared to a broader population of newly diagnosed patients with HF. Secondly, our study employed a retrospective study design, entailing data collection from medical records and hospital databases, which had inherent drawbacks leading to missing information in some instances, such as LVEF, NYHA, and drug prescriptions. Thirdly, our identification of newly diagnosed patients with HF relied solely on the ICD-10 coding system, which might have introduced a misclassification bias, potentially resulting in inaccuracies in the classification of newly diagnosed heart failure cases. Fourthly, some patients in this study were initially diagnosed in primary care settings and did not have LVEF) data available at the time of referral to the tertiary hospital. Due to time constraints and the potential for delays in re-diagnosis, the decision was made not to prioritize obtaining LVEF data for these patients. So, the absence of LVEF data for some patients is a limitation of the study. Fifthly, since the study was undertaken during the COVID-19 pandemic, it is possible that some patients had been admitted to another hospital in a different town or region. Lastly, our study did not include data on in-hospital treatment and management. Given that a significant proportion of deaths occurred after hospitalization, information concerning the quality of care during admission and post-hospital discharge is pivotal for improving the prognosis of patients with HF.