Clinical outcomes of fasting in patients with chronic heart failure with preserved ejection fraction: A prospective analysis

Fasting is a part of many world religions and in Islam fasting is obligatory for every adult Muslim during the month of Ramadan. Islam has exempted sick people from fasting; however, many people still partake in this activity. We investigated how Islamic fasting affects patients with heart failure with preserved ejection fraction (HFpEF). We enrolled 938 patients (fasting n = 456; non-fasting = 482) in this prospective observational study. The fasting group showed a decrease in NYHA functional class III (23.36% vs. 17.77%; p-value < 0.05) and IV (3.76% vs. 2.19%; p-value < 0.05), and an increase in class I(35.57% vs. 43.64%; p-value < 0.05). symptoms. This is an important area for physicians to advise patients with HFpEF to fast in the month of Ramadan as it can have a favorable effect on their symptoms and quality of life.


Introduction
Many world religions advocate periods of fasting, and in Islam fasting is obligatory for every adult Muslim during the month of Ramadan. Muslims are to abstain from taking anything per-oral or intranasally from dawn till dusk, a period which varies widely with geographical disparity and the season. Apart from food, medications and other intravenous nutrients are prohibited in Ramadan. Furthermore, there is an alteration of the routine sleep-wake cycle that can cause daytime malaise [1]. Although Islam exempts the sick and the unable from fasting, many Muslims partake in this activity during the religious month. Therefore, it is important to investigate how these changes affect patients with heart failure with preserved ejection fraction (HFpEF). Previous studies have investigated patients with decompensated heart failure with reduced ejection fraction (HFrEF); however, the subset of HFpEF has largely been under-evaluated [2,3].

Methods
In this prospective analysis, patients with the diagnosis of HFpEF and regular clinical follow-up were enrolled in this study from March to April 2022. Those who would fast in Ramadan were labeled Group 1 and those who would not as Group 2. All patients provided written, informed consent to participate in the study according to the World Medical Declaration of Helsinki. The basic demographic data (with anonymization of personal information), comorbid conditions, history of coronary artery disease (CAD), previous revascularization procedures, current medicines, and HF symptoms based on New York Heart Association (NYHA) functional class, during Ramadan fasting were recorded by the investigators. In addition, we also obtained the etiology of HF and previous history of cardiac implantable electronic device placement. All patients had their baseline hematology and biochemistry performed along with B-type natriuretic peptide (BNP), Troponin I, and lipid profile. In addition, an electrocardiogram (ECG) was performed to assess the heart rhythm and transthoracic echocardiography (TTE) was done to assess baseline ejection fraction (EF), left ventricular chamber size, the grade of diastolic dysfunction, valvular heart disease, and pulmonary artery systolic pressure. A follow-up of the clinical data was performed at the end of April by a repeat interview, laboratory tests, ECG, and TTE. The interview was conducted by a trained physician (W. A.) who obtained the following information: change in NYHA functional class, any change in HF symptoms, diet and medication compliance, hospitalizations, or emergency visits, and MACE.
HFpEF was defined as per the European Society of Cardiology 2021 HF guidelines: (i) symptoms ± signs of HF, (ii) EF ≥ 50%, (iii) objective evidence of cardiac and structural abnormalities consistent with left ventricular (LV) diastolic dysfunction/raised LV filling pressures, including raised BNP [4]. Medication non-compliance was defined as < 80% of HF pills taken for more than 7 days. Non-compliance to diet was defined as non-adherence to fluid and salt restriction as prescribed by the primary physician for more than 7 days. MACE included a composite of total death, myocardial infarction, stroke, hospitalization, and revascularization, including percutaneous coronary intervention. All data were extracted onto the statistical analysis software: Statistical Package for Social Sciences (SPSS) version 26 (IBM Corp., Armonk, NY.). Categorical variables were expressed as percentages (%), and continuous variables as mean ± standard deviation (SD). A Chi-square test was used to analyze categorical variables and Student's t-test and Mann-Whitney test were used for normal and abnormal distribution of continuous variables, respectively. A two-tailed p-value of <0.05 was considered significant.

Discussion
Ramadan fasting significantly affects the patient's lifestyle due to the reduced frequency of meals and subsequent consumption of the larger amount of calories at night. Notably, it is difficult to maintain more than 12 hours dosing intervals for several patient groups, including ischemic heart disease, hypertension, and lung diseases. Many studies have investigated the relationship between Ramadan fasting and cardiovascular (CV) diseases. A meta-analysis reported a positive effect of Ramadan fasting on CV risk factors [5]. Two other studies showed improved volume status in fasting patients, favorable effects on atrial fibrillation and lipid profile, and no effects on immediate or long-term outcomes [2,3]. There were several limitations, including the possibility of unmeasured confounding biases due to the observational nature of the study. However, our study represents the first and largest evaluation of the relation between fasting and HFpEF in South Asia.

Conclusion
The main clinical implication of this study is to advise cardiology physicians to advise patients with HFpEF to fast in the month of Ramadan as it can have a favorable effect on their symptoms and quality of life.

Consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.