case study 1 heart failure

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Chapter 5:  10 Real Cases on Acute Heart Failure Syndrome: Diagnosis, Management, and Follow-Up

Swathi Roy; Gayathri Kamalakkannan

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Case 1: Diagnosis and Management of New-Onset Heart Failure With Reduced Ejection Fraction

A 54-year-old woman presented to the telemetry floor with shortness of breath (SOB) for 4 months that progressed to an extent that she was unable to perform daily activities. She also used 3 pillows to sleep and often woke up from sleep due to difficulty catching her breath. Her medical history included hypertension, dyslipidemia, diabetes mellitus, and history of triple bypass surgery 4 years ago. Her current home medications included aspirin, atorvastatin, amlodipine, and metformin. No significant social or family history was noted. Her vital signs were stable. Physical examination showed bilateral diffuse crackles in lungs, elevated jugular venous pressure, and 2+ pitting lower extremity edema. ECG showed normal sinus rhythm with left ventricular hypertrophy. Chest x-ray showed vascular congestion. Laboratory results showed a pro-B-type natriuretic peptide (pro-BNP) level of 874 pg/mL and troponin level of 0.22 ng/mL. Thyroid panel was normal. An echocardiogram demonstrated systolic dysfunction, mild mitral regurgitation, a dilated left atrium, and an ejection fraction (EF) of 33%. How would you manage this case?

In this case, a patient with known history of coronary artery disease presented with worsening of shortness of breath with lower extremity edema and jugular venous distension along with crackles in the lung. The sign and symptoms along with labs and imaging findings point to diagnosis of heart failure with reduced EF (HFrEF). She should be treated with diuretics and guideline-directed medical therapy for congestive heart failure (CHF). Telemetry monitoring for arrythmia should be performed, especially with structural heart disease. Electrolyte and urine output monitoring should be continued.

In the initial evaluation of patients who present with signs and symptoms of heart failure, pro-BNP level measurement may be used as both a diagnostic and prognostic tool. Based on left ventricular EF (LVEF), heart failure is classified into heart failure with preserved EF (HFpEF) if LVEF is >50%, HFrEF if LVEF is <40%, and heart failure with mid-range EF (HFmEF) if LVEF is 40% to 50%. All patients with symptomatic heart failure should be started on an angiotensin-converting enzyme (ACE) inhibitor (or angiotensin receptor blocker if ACE inhibitor is not tolerated) and β-blocker, as appropriate. In addition, in patients with New York Heart Association functional classes II through IV, an aldosterone antagonist should be prescribed. In African American patients, hydralazine and nitrates should be added. Recent recommendations also recommend starting an angiotensin receptor-neprilysin inhibitor (ARNI) in patients who are symptomatic on ACE inhibitors.

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This case study involves a 76 year old female named Mary Lou Poppins, who presented to the ED accompanied by her son. She called her son after having symptoms of shortness of breath and confusion. Her past medical history includes hypertension, hyperlipidemia, coronary artery disease, and she was an everyday smoker for 30 years. She reports her home medications are lisinopril, simvastatin, and baby aspirin. Her current lifestyle includes: being a widow of six years, she lives alone, she walks her dog everyday, she drives to her knitting group three days a week, she makes dinner for her grandchildren once a week, she attempts to eat healthy but admits to consuming salty and high fat foods, and she insists on being very independent.

Mary Lou Poppins initial vitals in the emergency department includes a blood pressure of 138/70, heart rate of 108. respiratory rate of 26, temperature 98.9 degrees fahrenheit, and oxygen saturation of 84%. Her initial assessment included alert and oriented to person and place, dyspnea, inspiratory crackles in bilateral lungs, and a cough with pink frothy sputum. Her labs and diagnostics resulted in a BNP of 740 pg/ml, an echocardiogram showing an ejection fraction of 35%, an ECG that read sinus tachycardia, and a chest x-ray that confirmed pulmonary edema.

The Emergency Department physician diagnosed Mary Lou Poppins with left-sided heart failure. The orders included: supplemental oxygen titrated to keep saturation >93%, furosemide IV, enoxaparin subq, and metoprolol PO. Nursing Interventions included: monitoring oxygen saturation, adjusting oxygen route and dosage according to orders, assessing mentation and confusion, obtaining IV access, reassessing vitals, administering medications, and keeping the head of the bed elevated greater than 45 degrees. She was admitted to the telemetry unit for further stabilization, fluid balance monitoring, and oxygen monitoring.

On day one of hospital admission, Mary Lou Poppins required 4L of oxygen via nasal cannula in order to maintain the goal saturation of >93%. Upon assessment, it was determined that she was oriented to person and place. Auscultation of the lungs revealed bilateral crackles throughout, requiring collaboration with respiratory therapy once in the morning, and once in the afternoon. Physical therapy worked with the patient, but she was only able to ambulate for 100 feet. During ambulation, the patient had a decrease of oxygen saturation and dyspnea, requiring her oxygen to be increased to 6L. At the end of the day, strict intake and output monitoring showed an intake of 1200 mL of fluids, with an urinary output of 2L.

On day two of admission, Mary Lou began demonstrating signs of improvement. She only required 2 L of oxygen via nasal cannula with diminished crackles heard upon auscultation. Morning weight showed a weight loss of 1.3 lbs and the patient was oriented to person, place, and sequence of events. During physical therapy, she was able to ambulate 300 feet without required increased oxygen support. Daily fluid intake was 1400 mL with a urinary output of 1900 mL.

On the third and final day of admission, Mary Lou was AOx4 and did not require any type of oxygen support. When physical therapy arrived, the patient was able to ambulate 500 feet, which was close to her pre-hospital status. When the doctor arrived, the patient informed him that she felt so much better and felt confident going home. The doctor placed orders for discharge.

Upon discharge and throughout the patient’s hospital stay, Mary Lou Poppins was educated regarding the disease process of heart failure; symptoms to monitor for and report to her doctor; the importance of daily monitoring of weight, blood pressure, and heart rate; and the importance of adhering to a diet and exercise regime. Education was also provided regarding her medications and the importance of strictly adhering to them in order to prevent exacerbations of heart failure. Smoking cessation was also included in her plan of care. The patient received an informational packet regarding her treatment plan, symptoms to monitor for, and when to call her physician. Upon discharge, the patient was instructed to schedule a follow up appointment with her cardiologist for continued management of her care.

The patient was put in contact with a home health agency to help manage her care. The home health nurse will help to reinforce the information provided to the patient, assess the patient’s home and modify it to meet her physical limitations, and help to create a plan to meet daily dietary and exercise requirements. Regular follow-up appointments were stressed to Mary Lou Poppins in order to assess the progression of her disease. It will be important to monitor her lab values to also assess her disease progression and for any potential side effects associated with her medications. Repeat echocardiograms will be necessary to monitor her ejection fraction; if it does not improve with the treatment plan, an implanted cardiac defibrillator may be necessary to prevent cardiac death.

Open-Ended Questions

• What were the clinical manifestations that Mary Lou Poppins presented with in the ED that suggested the new onset of CHF?
• What factors most likely contributed to the onset of CHF?
• What patient education should Mary Lou Poppins receive on discharge in regards to managing her CHF?

Nursing Case Studies by and for Student Nurses Copyright © by jaimehannans is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License , except where otherwise noted.

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Case Study: Heart Failure Exacerbation Due to an Often Overlooked Cause

— shows importance of using wide differential when investigating hf.

by Kate Kneisel , Contributing Writer, MedPage Today

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study

Why has a 64-year-old man become increasingly short of breath over the past 2 weeks? That's what Sandra K. Rabat, DO, of A.T. Still University School of Osteopathic Medicine in Mesa, Arizona, and colleagues needed to determine, as they reported in Cureus .

The patient's medical history included a diagnosis of congestive heart failure and coronary artery disease in 2014, after stenting of his left anterior descending artery and right coronary artery. He also had high blood pressure and stage III chronic kidney disease (CKD) when he presented to the hospital for assessment after 2 weeks of worsening dyspnea.

The patient told clinicians he became winded even after a few steps, and that at night, he needed to prop himself up on three pillows to improve his breathing. He also had fluid retention in his lower legs, feet, and ankles that lasted all day, and continued to be worsening.

He said he was not aware of anything that might have exacerbated his shortness of breath, and that he did not use oxygen therapy or inhalers at home. He admitted that he was not consistent about taking his prescribed medications – carvedilol, lisinopril, furosemide, atorvastatin, and clopidogrel – and that that he sometimes forgot them entirely.

His family history was significant for premature coronary artery disease and the sudden cardiac death of his grandfather at age 49.

On questioning, he reported feeling that his heart beat was very rapid, but had no other observations. He said he did not use illicit drugs, smoke, or drink alcohol. Social determinants of the patient's health included experiencing homelessness, and he had very little social or family support.

Initial examination found that he was in a hypertensive emergency. His blood pressure was 220/110 mmHg and oxygen saturation was 84% oxygen on room air. Significant lab test findings included a creatinine level that was increased to 2.4 mg/dL from his baseline of 1.7 mg/dL. Troponins were 12,333 pg/ml and brain natriuretic peptide (BNP) was 1,431 pg/ml.

Clinicians noted the complexities of interpreting cardiac troponin levels and BNP in the setting of CKD. However, they said, "the magnitude of elevation of the troponins and BNP was very concerning for another process within the myocardium rather than being a false-positive elevation from CKD alone."

EKG findings included the following:

• Prolonged QTC interval
• Left-axis deviation
• Non-specific ST-T changes
• No ST-segment elevations

Chest x-ray showed that the patient had cardiomegaly with pulmonary edema. Given the high troponin levels and EKG results, the team ruled out ST-segment elevation myocardial infarction (STEMI) as a diagnosis in favor of non-ST-segment elevation myocardial infarction (NSTEMI).

In the emergency department, the patient was started on one dose of clonidine, nasal cannula oxygen, and heparin drip, and later also received hydralazine as needed for systolic blood pressure that exceeded 160 mmHg. In light of his elevated BNP levels and chest x-ray findings, the patient was admitted for acute exacerbation of congestive heart failure. Clinicians started the patient on aggressive diuresis with IV furosemide and accelerated his cardiac workup.

The workup for pulmonary embolus was unremarkable, given the patient's negative venous duplex and V/Q scan, the case authors noted. "Transthoracic echocardiogram revealed significant findings, including an estimated ejection fraction of 10% with moderate mitral regurgitation and moderate tricuspid regurgitation, a dilated right ventricle with severely impaired systolic function, and grade three diastolic dysfunction with restrictive filling."

The team noted that a previous echocardiogram performed about 2 years earlier showed that the patient's estimated ejection fraction had been 60% with preserved left ventricular systolic function. Because of the severity of his left ventricular dysfunction, and dilation of the left ventricle, the patient received a portable external cardiac defibrillator.

An ultrasound of his abdomen revealed bilateral renal atrophy with diffusely increased echogenicity bilaterally, which is indicative of CKD. Because he was in volume overload, clinicians continued his diuresis and closely monitored his creatinine levels.

After interval improvement of his kidney function, the patient underwent cardiac catheterization, which indicated "nonobstructive coronary artery disease and severe pulmonary hypertension."

Right heart hemodynamics revealed a mean pulmonary capillary wedge pressure of 40 mmHg, mean pulmonary artery pressure of 60 mmHg, and mean right atrial (RA) pressure of 32 mmHg, the case authors reported, noting that this ruled out nonischemic cardiomyopathy as a cause of the patient's acute decompensation.

Following the cardiac catheterization, the team discontinued diuretic treatment. The patient was started on dobutamine infusion at 5 mcg/kg/min, and the dose was titrated to achieve a minimum mean arterial pressure of 65 mmHg. He began taking isosorbide mononitrate and hydralazine, and continued with carvedilol.

Diuretic therapy with torsemide was reinstated. Treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor neprilysin inhibitor was contraindicated, due to the patient's medical status: acute kidney injury in the presence of CKD stage III and a glomerular filtration rate of less than 30 ml/min/1.73 m 2 .

Efforts to wean the patient off dobutamine, however, failed when his kidney function worsened to a creatinine level of 2.7 mg/dL, which the authors noted confirmed a need for inotropic support. When his kidney function improved, they started the patient on milrinone infusion with close monitoring, based on evidence of decompensated heart failure with low cardiac output and signs of end-organ hypoperfusion.

The objective was to combine milrinone infusion with standard heart failure therapy, including a beta-blocker, as tolerated. "The benefit of using milrinone over dobutamine in this patient's case is that milrinone, a phosphodiesterase inhibitor, will not antagonize a beta-blocker like dobutamine," the authors explained.

Because dobutamine's action is partly related to beta-1 and beta-2 adrenergic receptors, concomitant beta-blocker therapy would likely reduce the hemodynamic response to treatment, the team speculated. The patient was scheduled for a cardiac MRI, possibly to be followed by endomyocardial biopsy.

This proved to be unnecessary, however, when the test result came back as "positive for Coxsackie B viral antibody immunoglobulin G (IgG), indicating chronic viral infection," Rabat and co-authors said.

"This case highlights how viruses continue to be an underappreciated cause of heart failure. In fact, viral myocarditis is an underdiagnosed cause of acute heart failure and chronic dilated cardiomyopathy," as is iron deficiency anemia , the authors wrote.

Cardiomyopathy – which is associated with muscle or electrical dysfunction of the heart – is defined by the American Heart Association as a heterogeneous group of diseases of the myocardium, usually with inappropriate ventricular hypertrophy or dilatation.

Noting that viral myocarditis is often overlooked due to its varied presentation, Rabat and co-authors urged clinicians not to underestimate the substantial cardiovascular risks associated with a large spectrum of viral infections, some of which can lead to significant deterioration in decompensated patients.

"Coxsackie B virus is one of the most common causes of viral myocarditis and is responsible for 10-20% of all myocarditis and dilated cardiomyopathy cases," the case authors said. Parvovirus B19, adenovirus, Epstein-Barr virus, HIV, and COVID-19 have also been reported to cause myocarditis.

Viral myocarditis may go undiagnosed due to the wide variety of presentations, which can range from dyspnea to more aggressive symptoms suggestive of acute coronary syndrome. One review noted that among more than 3,000 patients with suspected acute or chronic myocarditis, dyspnea was found in 72%, chest pain in 32%, and arrhythmias in 18%.

"Myocarditis generally results from cardiotropic viral infection followed by active inflammatory destruction of the myocardium," the case authors stated. After the initial acute symptoms of viral myocarditis, the viral infection may either clear completely, persist, or "lead to a persistent auto-immune-mediated inflammatory process with long-term symptoms of heart failure."

A persistent viral infection of the myocardium can result in a progressive deterioration of left ventricular ejection fraction (LVEF), which likely explains the current patient's decline in LVEF from 60% to 10% over less than 2 years, Rabat and co-authors noted.

Despite being considered the diagnostic gold standard for acute or chronic inflammatory heart disease, endomyocardial biopsy is used infrequently because of the perception of associated risks and the absence of a widely accepted and sensitive histologic standard.

Endomyocardial biopsies may be complemented with use of liquid biopsy to monitor circulating biomarkers, including microRNAs (miRNAs), which have also demonstrated excellent diagnostic capability, the team noted. In fact, in a recent study , expression levels of miRNAs differentiated between patients with viral myocarditis, inflammatory cardiomyopathy, and healthy donors with a specificity of over 95%.

"However, further studies would be needed to elevate the routine use of miRNA-panel in addition to further guidelines to help optimize the management of this disease," the case authors wrote, noting that current guidelines advise optimal use of heart failure medications to manage symptoms.

Rabat and co-authors noted that the COVID-19 pandemic has brought to light a global sensitivity to viral infections. The pathogenesis of viral myocarditis in heart failure remains poorly understood and represents a significant global public health issue. The team urged clinicians investigating heart failure to maintain a wide index of suspicion and be aware "that even chronic Coxsackie B viral infection can cause an acute presentation of heart failure."

Read previous installments of this series:

Part 1: Heart Failure: A Look at Low Ejection Fraction

Part 2: Exploring Heart Failure With Preserved Ejection Fraction

Part 3: Heart Failure With Reduced Ejection Fraction: Diagnosis and Evaluation

Part 4: Case Study: Lightheadedness, Fatigue in Man With Hypertension

Part 5: Heart Failure With Preserved Ejection Fraction: Diagnosis and Evaluation

Part 6: Heart Failure Medical Management

Part 7: Managing Heart Failure Comorbidities

Kate Kneisel is a freelance medical journalist based in Belleville, Ontario.

Disclosures

The authors reported no conflicts of interest.

Primary Source

Source Reference: Rabat S K, et al "A case report on an underappreciated cause of heart failure: Chronic viral myocarditis" Cureus 2022; DOI: 10.7759/cureus.27253.

Heart Failure Case Studies

• First Online: 30 March 2023

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• Nicole R. Dellise 3 &
• K. Melissa Smith Hayes 4  

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Heart failure patients presenting to primary care clinics often have multiple, complex comorbidities. Several different disease processes and treatment options may need to be considered simultaneously in the setting of acute on chronic exacerbation of symptoms. This chapter will exemplify complex heart failure patient vignettes and provide practical guidance for the primary care provider, highlighting HF guideline-directed medical therapy.

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Director, Structural Heart Program, Director, Center for Advanced Heart Failure Therapy, Centennial Heart, Nashville, TN, USA

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Dellise, N.R., Hayes, K.M.S. (2023). Heart Failure Case Studies. In: Hayes, K.M.S., Dellise, N.R. (eds) Managing Heart Failure in Primary Care: A Case Study Approach. Springer, Cham. https://doi.org/10.1007/978-3-031-20193-6_19

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Case studies in heart failure

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• 1 Hickory Cardiology Associates, 1771 Tate Blvd. SE, Suite 201, Hickory, NC 28602, USA. [email protected]
• PMID: 14717398
• DOI: 10.1016/s0899-5885(02)00088-6

This article presents four case studies of patients with heart failure and the rationale for optimal treatment in each case.

Publication types

• Case Reports
• Activities of Daily Living
• Adrenergic beta-Antagonists / pharmacology
• Adrenergic beta-Antagonists / therapeutic use
• Carbazoles / pharmacology
• Carbazoles / therapeutic use
• Cardiac Catheterization
• Cardiotonic Agents / pharmacology
• Cardiotonic Agents / therapeutic use
• Diet, Sodium-Restricted
• Dyspnea / etiology
• Echocardiography
• Electrocardiography
• Fatigue / etiology
• Heart Failure / diagnosis
• Heart Failure / drug therapy*
• Heart Failure / etiology
• Metoprolol / pharmacology
• Metoprolol / therapeutic use
• Middle Aged
• Milrinone / pharmacology
• Milrinone / therapeutic use
• Phosphodiesterase Inhibitors / pharmacology
• Phosphodiesterase Inhibitors / therapeutic use
• Propanolamines / pharmacology
• Propanolamines / therapeutic use
• Treatment Outcome
• Vasodilator Agents / pharmacology
• Vasodilator Agents / therapeutic use
• Ventricular Function, Left / drug effects
• Adrenergic beta-Antagonists
• Cardiotonic Agents
• Phosphodiesterase Inhibitors
• Propanolamines
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Peer-reviewed

Research Article

Survival analysis of heart failure patients: A case study

Roles Conceptualization, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing

Affiliation Department of Statistics, Government College University, Faisalabad, Pakistan

Roles Data curation, Formal analysis, Methodology, Writing – original draft

Roles Conceptualization, Methodology, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Roles Formal analysis, Investigation, Methodology, Validation

Roles Methodology, Software, Visualization, Writing – review & editing

• Tanvir Ahmad, 
• Assia Munir, 
• Sajjad Haider Bhatti, 
• Muhammad Aftab, 
• Muhammad Ali Raza

• Published: July 20, 2017
• https://doi.org/10.1371/journal.pone.0181001
• Reader Comments

This study was focused on survival analysis of heart failure patients who were admitted to Institute of Cardiology and Allied hospital Faisalabad-Pakistan during April-December (2015). All the patients were aged 40 years or above, having left ventricular systolic dysfunction, belonging to NYHA class III and IV. Cox regression was used to model mortality considering age, ejection fraction, serum creatinine, serum sodium, anemia, platelets, creatinine phosphokinase, blood pressure, gender, diabetes and smoking status as potentially contributing for mortality. Kaplan Meier plot was used to study the general pattern of survival which showed high intensity of mortality in the initial days and then a gradual increase up to the end of study. Martingale residuals were used to assess functional form of variables. Results were validated computing calibration slope and discrimination ability of model via bootstrapping. For graphical prediction of survival probability, a nomogram was constructed. Age, renal dysfunction, blood pressure, ejection fraction and anemia were found as significant risk factors for mortality among heart failure patients.

Citation: Ahmad T, Munir A, Bhatti SH, Aftab M, Raza MA (2017) Survival analysis of heart failure patients: A case study. PLoS ONE 12(7): e0181001. https://doi.org/10.1371/journal.pone.0181001

Editor: Chiara Lazzeri, Azienda Ospedaliero Universitaria Careggi, ITALY

Received: February 26, 2017; Accepted: June 23, 2017; Published: July 20, 2017

Copyright: © 2017 Ahmad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Heart failure is the state in which muscles in the heart wall get fade and enlarge, limiting heart pumping of blood. The ventricles of heart can get inflexible and do not fill properly between beats. With the passage of time heart fails in fulfilling the proper demand of blood in body and as a consequence person starts feeling difficulty in breathing.

The main reason behind heart failure include coronary heart disease , diabetes , high blood pressure and other diseases like HIV, alcohol abuse or cocaine, thyroid disorders, excess of vitamin E in body, radiation or chemotherapy, etc. As stated by WHO [ 1 ] Cardiovascular Heart Disease (CHD) is now top reason causing 31% of deaths globally. Pakistan is also included in the list of countries where prevalence of CHD is increasing significantly. According to report by Al-Shifa hospital [ 2 ], 33% of Pakistani population above 45 has hypertension, 25% of patients over 45 years suffer diabetes mellitus, and CHD deaths in Pakistan has reached about 200,000 per year i.e. 410/100,000 of the population). All this results in increased prevalence of heart failure. Rate of heart failure patients in Pakistan is estimated to be 110 per million [ 1 ]. Rising stress of economic and social issues in the modern era, greasy food with little exercise results towards increased prevalence of heart failure in Pakistan.

Despite of this alarming situation, Pillai and Ganapathi [ 3 ] have reported that there are no reliable estimates of heart failure incidence and prevalence in this region while they are required due to poor and oily diet, lack of exercise and poor health care policies in this region. There are some projections based on prevalence data only from western countries.

In addition to relative scarcity of studies focusing on heart failure in this region, the present study has specific importance in the Pakistani context, as diet patterns in Pakistan are different with other the countries of South Asia like India, Bangladesh, Nepal and Sri Lanka.

The main objective of this study is to estimate death rates due to heart failure and to investigate its link with some major risk factors by choosing Faisalabad (third most populous city of Pakistan) as study area.

Detail of data

Current study is based on 299 patients of heart failure comprising of 105 women and 194 men. All the patients were more than 40 years old, having left ventricular systolic dysfunction and falling in NYHA class III and IV. Follow up time was 4–285 days with an average of 130 days. Disease was diagnosed by cardiac echo report or notes written by physician. Age, serum sodium, serum creatinine, gender, smoking, Blood Pressure (BP), Ejection Fraction (EF), anemia, platelets, Creatinine Phosphokinase (CPK) and diabetes were considered as potential variables explaining mortality caused by CHD. Age, serum sodium and CPK are continuous variables whereas EF, serum creatinine and platelets were taken as categorical variables. EF was divided into three levels (i.e. EF≤30, 30<EF≤45 and EF>45) and platelets was also divided into three level on the basis of quartiles. Serum creatinine greater than its normal level (1.5) is an indicator of renal dysfunction. Its effect on mortality was studied as creatinine >1.5 vs ≤1.5. Anemia in patients was assessed by their haematocrit level. Following McClellan et al. [ 4 ] the patients with haematocrit less than 36 (minimum normal level of haematocrit) were taken as anemic. The information related to risk factors were taken from blood reports while smoking status and blood pressure were taken from physician’s notes.

The study was approved by Institutional Review Board of Government College University, Faisalabad-Pakistan and the principles of Helsinki Declaration were followed. Informed consent was taken by the patients from whom the information on required characteristics were collected/accessed.

Statistical techniques

Due to the presence of censored data, survival analysis was used to estimate the survival and mortality rates. Kaplan & Meier [ 5 ] product limit estimator was used to make comparisons between survival rates at different levels explanatory variables. Cox regression as presented by Collett [ 6 ] was used to develop a model that can link the hazard of death for an individual with one or more explanatory variables and test the significance of these variables.

For determining the functional form of any particular independent variable following Fitrianto & Jiin [ 7 ] and Gillespie [ 8 ], plot of Martingale residuals versus different values (or levels) of a variable were used. The functional form of CPK was not linear therefore it was log transformed.

Following Pavlou et al. [ 9 ] model validation was assessed by bootstrapping [ 10 – 12 ] with 200 bootstrap replications. Internal validation of model was further checked by calculating calibration slope [ 13 ] for the average linear predictor. The calibration slope helped in estimating the ability of model for survival probability prediction. Discriminating ability of model was assessed by ROC curve [ 14 ]. A nomogram [ 15 ] was also built to predict the survival probabilities graphically.

Up to end of follow-up period, 96 (32%) patients died due to CHD. Table 1 , presents different baseline characteristics of dead and censored patients at the end of follow up period.

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The results of Cox regression model are presented in Table 2 . As Cox regression is semi parametric model, hence estimate of intercept (baseline hazard) was not provided by model fitting. According to Cox model, age was most significant variable.

https://doi.org/10.1371/journal.pone.0181001.t002

Coefficient concerning age indicated that chances of death due to CHD increase with growing age. Hazard of death due to CHD increases by 4% for every additional year of age. EF was another significant factor, hazard rate among patients with EF ≤30 was 67% and 59% higher as compared to the patients with 30<EF≤45 and EF≥45 respectively. In Fig 1(a) , Kaplan Meier survival curve was constructed for each level of EF. It is obvious that survival for EF ≤30 was lower than other two levels. Moreover, relatively small difference between the survival of patients with 30<EF<45 and EF≥45 can be observed. Serum creatinine was significant with p-value = 0.0026. It means death hazard gets more than double for unit increase in Serum creatinine. Serum sodium was significant with p-value = 0.0052 and its one unit (meq/L) increase decreases the hazard by 6%. Anemia was significant variable with p-value = 0.0096 and an anemic patient had 76% more chances of death as compared to non-anemic patient. According to results in Table 2 , gender, smoking, diabetes, CPK and platelets were found to be non-significant.

https://doi.org/10.1371/journal.pone.0181001.g001

Ejection fraction is an important measurement of how well one’s heart is pumping and is used to help classify heart failure and guide treatment. The EF is also found to be significant correlate of deaths among heart failure patients from Cox regression for present sample. Keeping its importance in view, EF is further analyzed through baseline characteristics ( Table 3 ) and Kaplan Meier curves ( Fig 1(a) ) which shows similar pattern as presented in Cox regression results.

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In Fig 1(b) , Kaplan Meier survival curves were constructed for both genders showed almost identical survival pattern.

Model validation

For model validation, calibration slope and ROC curve are developed from 200 bootstrapped samples. Calibration slope was equal to 0.96, which showed that model was not over fitted and predictions made by this model would neither be overestimated nor under estimated.

Discrimination ability was checked by ROC curve in Fig 2(a) . Area under the curve (AUC) was 0.81 at time of 250 days and 0.77 at time of 50 days thus it can be interpreted that the model was able to correctly recognize the event of death for 81% and 77% patients within 250 and 50 days respectively. It shows that discrimination ability of Cox model is higher at longer follow up time. The reason of this difference may be due to the violation of constant effect assumption of EF which is evident in Fig 2(b) which displays that effect of EF increases with the passage of time. As EF is highly significant for mortality (see Table 2 ), hence with passage of time model’s discrimination ability increases.

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Nomogram for prediction

Calibration slope and discrimination ability suggested that Cox model is able to predict probability of survival and hazard sufficiently. On the basis of these results, nomogram is presented in Fig 3 to provide the graphical predictions of probability after assigning different points to each independent variable with respect to their significance. Sum of these points provides an estimate of probability of survival.

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For example, an 80 year old non-smoker female diabetic patient with high blood pressure, EF = 40, haematocrit = 35, sodium = 140, creatinine = 5.2, platelets = 300 thousands and CPK = 3000 have points equal to 50+0+8+3+14+56+50+12+40+10+20 = 263 and probability of her survival is 0.60. The Cox model used for constructing this nomogram was fitted on original values of variables.

The statistical analysis identified age, EF, creatinine, sodium, anemia and BP as the significant variables affecting the likelihood of mortality among heart failure patients. Most of studies [ 16 – 17 ] supported the male gender as predictor of mortality among heart failure patients. However, like Román et al. [ 18 ] in this study odd ratio of men/women is not significant. With respect to significance and importance of variables the findings of the present study are more in lines with Rahimi et al. [ 19 ]. The results are found to be similar with other international studies like [ 20 – 23 ].

The findings that seem surprising are non-significance of smoking and diabetes. However, similar results concerning diabetes and smoking have been reported in other studies [ 24 – 25 ] as well. The reason behind may be smoking and diabetes are basically causes of heart problem at initial stages. We were only concerned with patients of NYHA class III and IV which are advanced stages of heart failure. Up to these stages, these factors (diabetes and smoking) may probably be controlled by medications and hence these factors do not have significant effect on deaths due to heart failure in class III and IV.

Performance of model was checked using calibration slope and ROC curve. Both concluded in adequacy of model for prediction. ROC curves were also used to discuss the goodness of model with respect to time. Nomogram was used to find the probability of survival by graphical method. It was observed that fall of survival probability was almost same for Kaplan Meier plot and nomogram.

It can be concluded that growing age, renal dysfunction (having serum creatinine greater than its normal level 1.5), high BP (higher than normal range), higher level of anaemia and lower values of ejection fraction (EF) are the key factors contributing towards increased risk of mortality among heart failure patients. Increased level of serum sodium can reduce the odds of death. No significant differences were found due to smoking status, diabetes and gender of patients.

Supporting information

S1 data. data_minimal..

https://doi.org/10.1371/journal.pone.0181001.s001

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