Our registry is a prospective observational analysis of heart failure patients from a single center in south India over a period of 1 year. Most available HF registries have classified patients based on the etiology or with respect to clinical presentation. Formerly, HF patients were classified based on LVEF as HFrEF and HFpEF. The 2016 ESC guidelines included HFmrEF as a distinct group to promote research in this gray area due to paucity of data [12]. The novelty of this registry lies in the projection of demographics, clinical characteristics, pharmacological management, and in-hospital outcome characteristics in LVEF-based subgroups as well as clinical phenotype-based subgroups.
As single-centered registries are limited and inconsistent, we compared our findings with multicenter registries. In comparison to other international cohorts, our study population was relatively a decade younger (59.9±13.3) [10, 13,14,15,16] and was comparable to THFR, a south Indian registry (61.2±13.7) and Indian subcontinent AHF patients in the Gulf acute heart failure registry (54±11) [4, 6]. The younger cohort in the Indian subset could possibly be due to higher prevalence of ischemic heart disease at a younger age in this geographical region, which might predispose for the development of HF [17].
HFrEF and HFmrEF made a substantial portion of the study population. The higher prevalence of HFrEF and HFmEF could be explained by the setting of our study, being hospital inpatients as opposed to HF registries [18] which included patients from outpatient clinics.
The study population predominantly comprised of male patients. This finding was in contrast to the USA-based ADHERE registry whereas it was in line with THFR and AFAR registries conducted in India [6, 7, 15]. This outlines increased risk factors for ischemic heart disease in males, leading to HF [19]. Male preponderance were higher in HFrEF and HFmrEF whereas the female dominance was higher in HFpEF group, which is in accordance with previous data [20].
A striking difference in the clinical presentation of patients was observed. Most of the patients in this registry presented with acute de novo HF. This finding was similar to the Indian cohort in an ethnic-based comparative study in HF patients conducted in the Middle East [4]. Our finding contradicts THFR in which only 39.8% of HF hospitalization was recorded to be acute de novo heart failure [6].
The burden of diabetes mellitus is high in South India and is a major risk factor for developing HF due to diffuse multivessel disease, recurrent MI, etc. [11]. Type II diabetes mellitus was thus unsurprisingly the most common comorbidity in patients with HFrEF and HFmrEF. As foreseen, hypertension was the most common comorbidity in HFpEF patients, which was in consensus to the study conducted by LyuSiqi, which evaluated the clinical characteristics and prognosis of HF based on LVEF [21].
CAD was the most common comorbidity across the entire spectrum of HF patients. CAD alone was noted in 52.5% of the patients, which was comparable to several international multicenter registries in which overall prevalence ranged from 40–61% [14, 15, 20]. It highlights the global IHD burden which could lead to cardiac remodeling and further progression to heart failure [22].
Echocardiographic findings in our registry showed a higher incidence of LVH and RV dysfunction in HFpEF group compared to other patients. These findings confirmed the fact that left ventricular hypertrophy due to systemic hypertension is an important cause for diastolic dysfunction and HFpEF [23].
The prevalence of anemia in the study cohort was 41.6%, which was more than comparable cohorts. The Swedish HF registry [24] reported a prevalence of anemia in 34% of the population and the HF registry of the “Get with the guideline” population [25] reported anemia in only 14% of the population. In this registry, anemia was more common in HFmrEF group. This contradicts the findings of previous research which estimated higher prevalence of anemia in higher EF [24, 25]. Importantly, iron deficiency was the most common cause of anemia in the study cohort (93.6%). Among the 24.9% of patients without anemia, iron deficiency was prevalent in 30.63%, which was comparable to another hospital-based observational study of the anemia profile in HF patients in India [26].
Although, not significant, hyponatremia and hypokalemia were observed in the study population were higher in the HFrEF group which could be attributed to the aggressive intravenous diuretic use (p>0.05), whereas hyperkalemia was found to be higher in the HFpEF group (p=0.416).
Dietetic and therapeutic non-compliance was the most common precipitating factor for HF hospitalization in the entire study population. This finding reflects the need of multidisciplinary chronic disease management clinics and patient counseling to reinforce medication and dietary adherence.
It was found that the usage of guideline-directed medical therapy (GDMT) in HFrEF patients in our study higher than comparable cohort in India [6, 27]. A multidisciplinary HF team and an on-going clinical audit of discharge prescriptions for evidence-based medication in HF have been proven to uplift the quality of HF management, which is being adopted at our center [28].
About 13.1% of patients in the HFrEF group and 7.7% of patients in the HFmrEF group were initiated on inotropes, whereas none of the patients in the HFpEF group had undergone inotropic treatment. The usage of inotrope in hospital was similar to THFR [6].
India, being a low-middle income country, ICD and CRT rates in the study population were minimal as opposed to other HF registries. Though eligible patients were offered device therapy, because of financial reasons the number of patients who underwent device therapy was noted to be low in our registry.
The overall mortality rate of HF patients over a period of 1 year in this study was 2%, opposed to higher mortality rates in several previously published data. The in-hospital mortality was comparable in all the three EF based subgroups (p>0.05). This result is inconsistent with previous research in which the prognosis of the HFmrEF group was intermediate to HFrEF and HFpEF [29, 30].
Reduced EF was associated with longer length of hospital stay (p=0.000); probably due to higher fluid overload requiring aggressive intravenous diuretic use, diuretic resistance, and time required to stabilize patients on GDMT. The difference between the LVEF-based subgroups in terms of NYHA IV symptoms at the time of discharge was statistically not significant (p>0.05). Worsening renal function at the time of discharge of the HF patients in our study was significantly more in HFrEF group (p=0.042). This reflects diuretic or ACEI-induced acute kidney injury and higher incidence of hypoperfusion in this subgroup.
Association of in-hospital mortality with the clinical phenotype of patients showed a higher rate of in-hospital deaths in cold and wet phenotype (p=0.000), confirming that hypoperfusion is a marker of HF severity is associated with poor outcomes [31, 32]. Length of stay in the hospital significantly exceeded in patients with warm and wet phenotype (p=0.000), which can be attributed to the intravenous diuretic use. Worsening renal function in the hospital was also noted to be higher in cold and wet phenotype (p=0.001) probably due to associated hemodynamic changes. The NYHA IV symptoms among patients did not vary significantly between the clinical phenotype-based subgroups.
This study has limitations inherent to most observational studies. It was a single-center study and data was collected by a single observer. We failed to comprehensively compare our findings with other indian hospital-based registries, and as to date, there is no single center or multicentre national registries in India that has elaborated on clinical characteristics and outcomes of patients based on LVEF and clinical phenotype. Details about a target dose of mandated drugs and follow-up data of patients were not extracted in this study. Cardiac rehabilitation of in-hospital patients, including 6 minute walk distance and cardiopulmonary exercise test (CPET) were not feasible in all patients; hence, the data were not included in the registry.