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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 108-113

Clinical, echocardiographic profile, and outcome of heart failure patients with preserved ejection fraction


1 Department of Cardiology, Government Medical College, Kottayam, Kerala, India
2 Department of Cardiology, Government Medical College, Ernakulam, Kerala, India

Date of Submission15-May-2021
Date of Decision08-Jul-2021
Date of Acceptance09-Jul-2021
Date of Web Publication25-Aug-2021

Correspondence Address:
Dr. Jayaprasad Narayanapillai
Department of Cardiology, Government Medical College, Kottayam, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_81_21

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  Abstract 


Context: Approximately half of the patients with heart failure have preserved ejection fraction (HFpEF). Epidemiologic studies and randomized trials provide somewhat conflicting data regarding outcomes of HFpEF.
Aims: The objective is to study the clinical and echocardiographic profile of patients admitted with HFpEF and estimate outcomes.
Settings and Design: This is a prospective observational study on patients with new-onset HF requiring hospitalization and normal EF and evidence of diastolic dysfunction in echocardiography.
Subjects and Methods: Risk factors for HFpEF, clinical features, and echocardiographic parameters were recorded. The primary outcome studied was mortality at 1 year and the secondary outcome was rehospitalization at 1 year.
Statistical Analysis Used: Variables were analyzed using Student's t-test and Chi-square test. Univariate and multivariate analysis were done to find out predictors of outcomes.
Results: A total of 104 patients admitted with the first episode of HF were found to have left ventricular ejection fraction ≥ 50% and diastolic dysfunction. Associated cardiac conditions were hypertension in 77.8%, diabetes in 38.5%, ischemic heart disease in 30.7%, and atrial fibrillation in 32.7%. In our study, 42 patients (40.1%) had rehospitalization within 1 year. The mortality rate at 1 year was 15.4% (16 patients). The parameters found to be significantly correlated with mortality in the univariate analysis included age, high BP, anemia, hyponatremia, low isovolumetric relaxation time, and higher E/e' ratio. Multivariate analysis showed advanced age, hyponatremia, and high E/e' to be independent predictors of mortality.
Conclusions: Among hospitalized patients with new-onset HFpEF annual mortality rate is as high as 15.4%. Advanced age, hyponatremia, and high E/e' were found to be independent predictors of mortality.

Keywords: Diastolic dysfunction, echocardiography, heart failure, hospitalisation, mortality


How to cite this article:
John M C, Narayanapillai J, Madhavan S, Jayaprakash V L, George R. Clinical, echocardiographic profile, and outcome of heart failure patients with preserved ejection fraction. Heart India 2021;9:108-13

How to cite this URL:
John M C, Narayanapillai J, Madhavan S, Jayaprakash V L, George R. Clinical, echocardiographic profile, and outcome of heart failure patients with preserved ejection fraction. Heart India [serial online] 2021 [cited 2021 Oct 27];9:108-13. Available from: https://www.heartindia.net/text.asp?2021/9/2/108/324614




  Introduction Top


Heart failure (HF) is a clinical syndrome resulting from structural and functional impairment of ventricular filling or ejection of blood. The prevalence of HF is increasing in both developed and developing countries as a result of advancing age and better survival of various cardiac disorders with therapy. Approximately half of the HF patients have heart failure with preserved ejection fraction(HFpEF) defined as left ventricular ejection fraction EF ≥50%.[1] Compared to patients with HF and reduced EF (HFrEF), those with HFpEF are older, more likely to be women and more commonly have a history of hypertension and atrial fibrillation (AF), while a history of myocardial infarction is less common.[2],[3]

The diagnosis of HFpEF is challenging compared to HFrEF. Signs and symptoms for HF are often nonspecific and do not discriminate well between HF and other clinical conditions. The clinical diagnosis needs to be supported by objective measures of cardiac dysfunction at rest or during exercise. Major structural alterations include increased left atrial volume index and left ventricular mass index. Functional alterations include measures of diastolic dysfunction demonstrated by mitral inflow Doppler velocities, tissue Doppler indices, pulmonary venous Doppler indices, and tricuspid regurgitation velocities.

The 5-year survival rate for HF is <50% regardless of EF.[4] Over the last 30 years, improvements in treatments have improved survival and reduced hospitalization rate in HFrEF whereas they remain unchanged for HFpEF.[5] Epidemiologic studies and randomized trials provide somewhat conflicting data regarding mortality of HFpEF. Epidemiologic studies showed an annual mortality rate around 20%–30%.[6],[7] whereas randomized controlled trials showed a lower all-cause mortality rate of about 5%–10% for HFpEF.[8],[9],[10],[11] The majority of deaths in HFpEF are cardiovascular related, comprising 51%–60% of deaths in epidemiological studies and about 70% in clinical trials.[12] The proportion of noncardiac death is more in HFpEF compared to HFrEF due to advanced age and comorbidities.

Though studies have identified numerous prognostic markers of death and/or HF hospitalization in patients with HFpEF, precise risk stratification in HF remains challenging.[4],[7] Considering the above facts we planned to conduct a hospital-based study to obtain the clinical and echocardiographic profile of patients admitted with HFpEF. We also aimed to study the prognosis of these patients by analyzing the mortality and hospitalization rate at 1 year of follow-up.


  Subjects and Methods Top


Our study was a prospective observational study done in the Cardiology department of a tertiary care hospital. The study protocol was approved by the institutional ethics committee of the hospital before the initiation of the study. We have enrolled consecutive patients admitted for the first episode of HF in the cardiology department for the study. The patients were included in the study if they satisfied the following criteria.

  1. Signs and symptoms of HF satisfying Framingham criteria for HF
  2. LV EF ≥50% by two-dimensional (2-D) echocardiography
  3. Presence of left ventricular diastolic dysfunction.


Exclusion criteria included the following: (1) sub-optimal echo window, (2) severe anemia (hemoglobin [Hb] <8 g/dl), (3) severe valvular heart disease or prosthetic valve, (4) patients on the ventricular pacemaker.

All patients were evaluated by detailed history, clinical examination, and relevant blood investigations including Hb, renal function tests, and serum electrolytes. Baseline demographic data and data of clinical risk factors were collected. Hypertension was defined as systemic blood pressure ≥140/90 mmHg or the use of antihypertensive treatment. Diabetes mellitus was defined as fasting blood sugar ≥126 mg/dl or the use of antidiabetic treatment. Coronary artery disease (CAD) was defined as the history of previous myocardial infarction, acute coronary syndrome, exertional angina with ischemia on noninvasive evaluation, prior revascularization, or CAD confirmed by coronary angiography. Renal insufficiency was defined as a calculated creatinine clearance rate of <60 mL/min as determined by the Cockcroft-Gault equation.

All patients underwent 12-lead electrocardiography (ECG), chest radiography, and 2-D echocardiography. Detailed echocardiography examination was done using Vivid E9, GE Vingmed Ultrasound AS, Norway. The echocardiographic parameters studied were: (1) chamber dimensions (LA diameter, left ventricular internal diameter end diastole and left ventricular internal diameter end systole), (2) left ventricular ejection fraction (LVEF) (3) Pulsed wave Doppler parameters-mitral E velocity, A velocity and E/A ratio (4) tissue Doppler parameters-e' velocity, a' velocity, E/e' ratio, (5) time intervals like isovolumetric relaxation time (IVRT), and mitral deceleration time (DT). Diastolic dysfunction was diagnosed by E/A ratio, E/e' ratio, mitral DT, IVRT, and pulmonary venous flow pattern.[13] Patients with diastolic dysfunction were grouped into four grades based on the above parameters. (Grade1:Impired relaxation characterised by E/A ratio ≤0.8, E/e' <10, DT >240 ms, Grade 2: Pseudo-normal pattern characterised by E/A ratio >0.8 to <2, E/e' 10–14, DT >140 ms, Grade 3: reversible restrictive pattern characterised by E/A ratio ≥2, E/e' ≥14, DT <140 ms, Grade 4: Fixed restrictive pattern-E/A ratio >2, E/e' ≥14, DT <140 ms.). Patients were followed up for primary and secondary outcomes. The primary outcome studied was mortality at 1 year and the secondary outcome was rehospitalization at 1 year assessed by the out-patient clinic or by telephone interview.

Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS; Chicago, IL, USA). Continuous variables were expressed as means and standard deviation and were compared between groups by Student's t-test. Categorical variables were summarized by frequency per cents and analyzed with Chi-square test. The level of statistical significance was P < 0.05. Univariate and multivariate analysis were done to find out predictors of primary and secondary outcomes.


  Results Top


Baseline data

A total of 104 patients admitted with the first episode of HF were found to have LVEF ≥50% and diastolic dysfunction by 2-D echocardiography. There were 54 females (51.9%) and 50 males (48.1%). The mean age of the study population was 59.9 ± 11.7 years (range- 36 to 88 years). The maximum number of patients were in the age group 60–69 years (43, 41.3%). The mean body mass index (BMI) was 24.1 ± 3.3. Out of 104 patients, 44 (42.3%) were overweight and 4 (3.8%) were obese. Clinical variables including etiological factors and frequency of various symptoms and signs are given in [Table 1].
Table 1: Etiological factors, clinical and electrocardiography features of the study population

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Electrocardiography and chest radiograph Abnormalities

Left ventricular hypertrophy (LVH) was the most common ECG abnormality. LVH was present in 67 patients (64.4%). AF was present in 34 (32.7%). Left atrial enlargement was seen in 62 (59.6%) patients. Left bundle branch block was seen in five patients (4.8%). Chest radiograph showed cardiomegaly in 64 (61.5%) of patients.

Echocardiographic parameters

Detailed echocardiographic study was done in all patients. Mean LVEF was 61.43 ± 6.79%. The mean E/A ratio was 1.9 and mean E/e' ratio was 16.8 ± 4.8. Of the 104 patients, 8 (7.7%) had Grade 1 LV diastolic dysfunction and 36 (34.6%) had Grade 2 diastolic dysfunction or pseudo-normal pattern. Grade 3 diastolic dysfunction was present in 28 (26.9%) and Grade 4 diastolic dysfunction was present in 32 (30.7%) of the patients. Pulmonary artery hypertension was present in 71 (68.3%) of patients. Mean PA pressure was 48 ± 16 mm of Hg. Mean values of different echocardiographic parameters among the four grades of diastolic dysfunction are given in [Table 2].
Table 2: Echocardiographic parameters in the study population

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Outcomes

Mortality

At the end of 1 year of follow-up 16 (15.4%) patients died in the study population. Clinical, laboratory, and echocardiographic parameters were compared among patients with and without mortality. New York Heart Association (NYHA) functional class, pulmonary edema at presentation were significantly correlated with mortality. The severity of diastolic dysfunction also predicted mortality. All deaths occurred in patients with diastolic dysfunction Grade 3 and 4, whereas none of the patients with Grade 1 and 2 diastolic dysfunction died. Univariate analysis showed advanced age, high BP, low Hb and serum sodium, low IVRT and higher E/e' ratio to be significantly correlated with mortality. The various predictors of mortality are given in [Table 3].
Table 3: Predictors of mortality in the study population

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Multivariate binary logistic regression analysis was done to find out independent predictors of mortality. Among the various parameters advanced age (P = 0.038, Hazard Ratio (HR) =1.3, 95% confidence interval C.I. =1.013–1.550), low serum sodium (P = 0.003, HR = 0.51, 95% C.I. =0.331–0.800) and high E/e' (P = 0.03, HR = 1.78, 95% C.I. =1.058–2.990) were the only independent predictors of mortality. Among the deaths, majority (n = 11,68.7%) were cardiac. Sudden cardiac death occurred in four patients (36% of cardiovascular mortality) whereas progressive HF was the cause in five patients (45% of CV mortality). One patient died due to myocardial infarction and another due to stroke. Most common noncardiac mortality was cancer related (n = 3).

Rehospitalization

Among the 104 patients, 42 (40.1%) had rehospitalization within 1 year. The various clinical and echocardiographic factors predictive of rehospitalization were analyzed. Among the clinical parameters, pulmonary edema at initial presentation was the only parameter predictive of rehospitalization. Among patients with rehospitalization 69.7% had initial presentation with pulmonary edema compared with 43.7% in those without rehospitalization (P = 0.013). Rehospitalization was more in patients with higher grades of diastolic dysfunction. Among eight patients with diastolic dysfunction Grade 1, none were admitted again in the hospital. The percentage of patients with rehospitalization among Grades 2, 3 and 4 of diastolic dysfunction were 25%, 46.4%, and 62.5%, respectively. NYHA functional class was also predictive of rehospitalization. Out of NYHA Class 1 and two patients, 11 (20.7%) had rehospitalization, whereas 31 (58.4%) patients had rehospitalization among 51 patients in NYHA Class 3 and 4. Various parameters are compared among those with and without rehospitalization in [Table 4]. Among the continuous variables age, systolic blood pressure (SBP), IVRT, and E/e' were predictive of rehospitalization.
Table 4: Variables and rehospitalization

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Multivariate binary logistic regression analysis was done to find out independent predictors of rehospitalisation. Advanced age (P = 0.028, HR = 1.062, 95% C.I. =1.007–1.121), SBP (P = 0.020, HR = 1.059, 95% CI = 1.009–1.111) and high E/e' (P = 0.045, HR = 1.302, 95% CI = 0.996–1.702) were the only independent predictors of rehospitalization.


  Discussion Top


HFpEF represents a major epidemiological problem, representing almost 50% of patients hospitalized for HF. We prospectively studied consecutive patients admitted for the first time with a diagnosis of EFpEF by echocardiography. In the present study, we have made an attempt to study the clinical and echocardiographic profile and 1 year clinical outcomes of diastolic HF. We also made an attempt to find out the predictors of mortality and rehospitalization.

Etiology and clinical characteristics of heart failure regarding ejection fraction

The proportion of HFpEF among patients with HF varies widely from 13% to 74% depending on the diagnostic criteria and patient population. These patients tend to be older and more often are women with a high prevalence of hypertension.[14],[15] In the present study, the mean age of the study population was 59.9 ± 11.7, the highest age was 88 years and the maximum number of patients was in the age group of 60–69 years (41.3%). Incidence of HFpEF increases with age, as a result of increased comorbidities and structural changes associated with normal aging on the cardiovascular system. LVH and fibrous tissue replacement of myocytes associated with hypertension and ischemic heart disease contribute to this phenomenon. In the present study, 51.9% of patients were females. Hypertension was the most commonly associated cardiac condition in patients with HFpEF. In our study 77.8% of patients had hypertension. The prevalence of diabetes in patients with HFpEF is around 30%–40%.[16] In the current study, out of 104 patients with diastolic dysfunction, 40 (38.5%) were diabetics. Obesity and dyslipidemia are established risk factors for HF. In our study mean BMI was 24.1 ± 3.3 kg/m2. About 46% had overweight or obesity and a similar percentage had dyslipidemia. Ischemic heart disease was present in 32 patients (30.7%). In our study, out of 104 patients, 25 (24%) had chronic kidney disease. Seven patients had restrictive cardiomyopathy which included 3 cases of amyloidosis, 3 cases of endomyocardial fibrosis, and one case of hyper-eosinophilic syndrome. AF was present in 32.7% of patients.

In HFpEF, breathlessness is frequently the earliest symptom due to pulmonary congestion.[17] Signs and symptoms of congestive HF are usually present in most patients hospitalized for decompensated HF or episodes of pulmonary edema. In our study, dyspnea was the most common symptom (92.3%). Pulmonary edema occurred in about 52% of patients. Pulmonary edema at initial hospitalization was predictive of mortality and rehospitalization in our study.

Diastolic dysfunction

In this study, 7.7% of patients had Grade 1 LV diastolic dysfunction and 34.6% had Grade 2 diastolic dysfunction. Grade 3 diastolic dysfunction was present in 26.9% Grade 4 diastolic dysfunction was present in 30.7% of the patients. Pulmonary artery hypertension was present in 68.3% of patients. Mitral annular velocities (e') can be used to draw inferences about LV relaxation and along with mitral peak E velocity (E/e' ratio) can be used to predict LV filling pressures. Using the E/e' ratio, a ratio <8 is usually associated with normal LV filling pressures, whereas a ratio ≥14 is associated with increased LV filling pressures.[13] In the present study, the mean E/e' ratio in different grades of diastolic dysfunction was 8.97 in Grade 1, 13.0 in Grade 2, 17.62 in Grade 3, and 21.74 in Grade 4. Among echocardiographic parameters, low IVRT and high E/e' were predictive of rehospitalization and mortality.

Prognosis in patients with heart failure regarding ejection fraction

In our study, 42 patients (40.7%) had rehospitalization in 1 year. Pulmonary edema at initial presentation was predictive of both rehospitalization and mortality. Mortality and rehospitalization were more in patients with higher grades of diastolic dysfunction. Among patients with Grade 3 and 4 diastolic dysfunction 55% had rehospitalization. The mortality rate among patients with diastolic dysfunction Grade 2 and 3 was 26.6%. None of the patients with Grade 1 and 2 diastolic dysfunction died. NYHA functional class was also predictive of rehospitalization and mortality. Other predictors of rehospitalization include age, SBP, and echocardiographic parameters like IVRT and high E/e'. After multivariate analysis age, SBP, and E/e' were found to be independent predictors of rehospitalization.

The mortality burden in patients with HFpEF varies considerably, ranging from 10% to 30%.[12] In the study by Tribouilloy et al., the 1-, 3-, and 5-year mortality rates in patients admitted for the first episode of HFpEF were 22%, 42%, and 57%, respectively. Older age, stroke, chronic obstructive pulmonary disease, diabetes, cancer, hyponatremia, and low glomerular filtration rate were predictors of 5 years mortality in the preserved EF group.[4] In another study, among hospitalized patients with new-onset HF, 1-year predictor of mortality in patients with preserved EF were age, SBP, hyponatremia, anemia, renal dysfunction, and comorbidities.[6] In our study, the mortality rate at 1 year was 15.4%. The parameters found to be significantly correlated with mortality in the univariate analysis included age, high BP, anemia, hyponatremia, low IVRT, and higher E/e' ratio. Multivariate analysis showed advanced age, hyponatremia, and high E/e' to be independent predictors of mortality.

Cardiovascular deaths constitute the majority of deaths in both HFpEF and HFrEF. The proportion of cardiac deaths is higher in HFrEF than in HFpEF. Cardiac deaths constituted about 70% of total deaths in HFpEF in randomized trials[18],[19] while about 50% in epidemiological studies.[20],[21] Sudden death accounts for up to 25% of all-cause mortality and 40% of CV mortality in HFpEF trials. Worsening HF accounts for 20%–30% of total CV deaths in recent HFpEF trials.[22] Cancer was the most common non-CV cause of death in studies, others including sepsis and respiratory causes.[20],[23] In our study, cardiac deaths accounted for 68.7% of total deaths. Sudden cardiac death accounted for 36% of CV mortality whereas progressive HF accounted for 45% of CV mortality.

Limitations

Major limitation of the study is that it is hospital based that too conducted on in-patients. The sample size is relatively small. Novel echocardiographic markers like strain imaging were not utilized. We did not study the effect of various medications on survival.


  Conclusions Top


In this prospective study on hospitalized HF patients, HFpEF was more in the elderly and had associated hypertension, diabetes mellitus, and ischemic heart disease as comorbidities. Our sample population had 15.4% mortality and 40.1% rehospitalization at 1-year follow-up. Advanced age, hyponatremia, and high E/e' were independent predictors of mortality.

Authors' contributions

All authors are actively involved in research design, data acquisition, data analysis, interpretation, manuscript preparation and revision.

Ethical approval

The study was approved by institutional ethics committee, REF- IRB-no 17/2017/KMC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.







 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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