a case study on 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 review, case discussion.

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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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Article Contents

Introduction, case presentation.

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Clinical case: heart failure and ischaemic heart disease

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Giuseppe M C Rosano, Clinical case: heart failure and ischaemic heart disease, European Heart Journal Supplements , Volume 21, Issue Supplement_C, April 2019, Pages C42–C44, https://doi.org/10.1093/eurheartj/suz046

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Patients with ischaemic heart disease that develop heart failure should be treated as per appropriate European Society of Cardiology/Heart Failure Association (ESC/HFA) guidelines.

Glucose control in diabetic patients with heart failure should be more lenient that in patients without cardiovascular disease.

Optimization of cardiac metabolism and control of heart rate should be a priority for the treatment of angina in patients with heart failure of ischaemic origin.

This clinical case refers to an 83-year-old man with moderate chronic obstructive pulmonary disease and shows that implementation of appropriate medical therapy according to the European Society of Cardiology/Heart Failure Association (ESC/HFA) guidelines improves symptoms and quality of life. 1 The case also illustrates that optimization of glucose metabolism with a more lenient glucose control was most probably important in improving the overall clinical status and functional capacity.

The patient has family history of coronary artery disease as his brother had suffered an acute myocardial infarction (AMI) at the age of 64 and his sister had received coronary artery by-pass. He also has a 14-year diagnosis of arterial hypertension, and he is diabetic on oral glucose-lowering agents since 12 years. He smokes 30 cigarettes per day since childhood.

In February 2009, after 2 weeks of angina for moderate efforts, he suffered an acute anterior myocardial infarction. He presented late (after 14 h since symptom onset) at the hospital where he had been treated conservatively and had been discharged on medical therapy: Atenolol 50 mg o.d., Amlodipine 2.5 mg o.d., Aspirin 100 mg o.d., Atorvastatin 20 mg o.d., Metformin 500 mg tds, Gliclazide 30 mg o.d., Salmeterol 50, and Fluticasone 500 mg oral inhalers.

Four weeks after discharge, he underwent a planned electrocardiogram (ECG) stress test that documented silent effort-induced ST-segment depression (1.5 mm in V4–V6) at 50 W.

He underwent a coronary angiography (June 2009) and left ventriculography that showed a not dilated left ventricle with apical dyskinesia, normal left ventricular ejection fraction (LVEF, 52%); occlusion of proximal LAD, 60% stenosis of circumflex (CX), and 60% stenosis of distal right coronary artery (RCA). An attempt to cross the occluded left anterior descending (LAD) was unsuccessful.

He was therefore discharged on medical therapy with: Atenolol 50 mg o.d., Atorvastatin 20 mg o.d., Amlodipine 2.5 mg o.d., Perindopril 4 mg o.d., oral isosorbide mono-nitrate (ISMN) 60 mg o.d., Aspirin 100 mg o.d., metformin 850 mg tds, Gliclazide 30 mg o.d., Salmeterol 50 mcg, and Fluticasone 500 mcg b.i.d. oral inhalers.

He had been well for a few months but in March 2010 he started to complain of retrosternal constriction associated to dyspnoea for moderate efforts (New York Heart Association (NYHA) II–III, Canadian Class II).

For this reason, he was prescribed a second coronary angiography that showed progression of atherosclerosis with 80% stenosis on the circumflex (after the I obtuse marginal branch) and distal RCA. The LAD was still occluded.

After consultation with the heart team, CABG was avoided because surgical the risk was deemed too high and the patient underwent palliative percutaneous coronary intervention (PCI) of CX and RCA. It was again attempted to cross the occlusion on the LAD. But this attempt was, again, unsuccessful. Collateral circulation from posterior interventricular artery (PDL) to the LAD was found. The pre-PCI echocardiogram documented moderate left ventricular dysfunction (EF 38%), the pre-discharge echocardiogram documented a LVEF of 34%. Because of the reduced LVEF, atenolol was changed for Bisoprolol (5 mg o.d.).

At follow-up visit in December 2012, the clinical status and the haemodynamic conditions had deteriorated. He complained of worsening effort-induced dyspnoea/angina that now occurred for less than a flight of stairs (NYHA III). On clinical examination clear signs of worsening heart failure were detected ( Table  1 ). His medical therapy was modified to: Bisoprolol 5 mg o.d., Atorvastatin 20 mg o.d., Amlodipine 2.5 mg o.d., Perindopil 5 mg o.d., ISMN 60 mg o.d., Aspirin 100 mg o.d., Metformin 500 mg tds, Furosemide 50 mg o.d., Gliclazide 30 mg o.d., Salmeterol 50 mcg oral inhaler, and Fluticasone 500 mcg oral inhaler. A stress perfusion cardiac scintigraphy was requested and revealed dilated ventricles with LVEF 19%, fixed apical perfusion defect and reversible perfusion defect of the antero-septal wall (ischaemic burden <10%, Figure  1 ). He was admitted, and an ICD was implanted.

Clinical parameters during follow-up visits

Myocardial perfusion scintigraphy and left ventriculography showing dilated left ventricle with left ventricular ejection fraction 19%. Reversible perfusion defects on the antero-septal wall and fixed apical perfusion defect.

In March 2013, he felt slightly better but still complained of effort-induced dyspnoea/angina (NYHA III, Table  1 ). Medical therapy was updated with bisoprolol changed with Nebivolol 5 mg o.d. and perindopril changed to Enalapril 10 mg b.i.d. The switch from bisoprolol to nebivolol was undertaken because of the better tolerability and outcome data with nebivolol in elderly patients with heart failure. Perindopril was switched to enalapril because the first one has no indication for the treatment of heart failure.

In September 2013, the clinical conditions were unchanged, he still complained of effort-induced dyspnoea/angina (NYHA III) and did not notice any change in his exercise capacity. His BNP was 1670. He was referred for a 3-month cycle of cardiac rehabilitation during which his medical therapy was changed to: Nebivolol 5 mg o.d., Ivabradine 5 mg b.i.d., uptitrated in October to 7.5 b.i.d., Trimetazidine 20 mg tds, Furosemide 50 mg, Metolazone 5 mg o.d., K-canrenoate 50 mg, Enalapril 10 mg b.i.d., Clopidogrel 75 mg o.d., Atorvastatin 40 mg o.d., Metformin 500 mg b.i.d., Salmeterol 50 mcg oral inhaler, and Fluticasone 500 mcg oral inhaler.

At the follow-up visit in January 2014, he felt much better and had symptomatically, he no longer complained of angina, nor dyspnoea (NYHA Class II, Table  1 ). Trimetazidine was added because of its benefits in heart failure patients of ischaemic origin and because of its effect on functional capacity. Ivabradine was added to reduce heart rate since it was felt that increasing nebivolol, that was already titrated to an effective dose, would have had led to hypotension.

He missed his follow-up visits in June and October 2014 because he was feeling well and he had decided to spend some time at his house in the south of Italy. In January and June 2015, he was well, asymptomatic (NYHA I–II) and able to attend his daily activities. He did not complain of angina nor dyspnoea and reported no limitations in his daily activities. Unfortunately, in November 2015 he was hit by a moped while on the zebra crossing in Rome and he later died in hospital as a consequence of the trauma.

This case highlights the need of optimizing both the heart failure and the anti-anginal medications in patients with heart failure of ischaemic origin. This patient has improved dramatically after the up-titration of diuretics, the control of heart rate with nebivolol and ivabradine and the additional use of trimetazidine. 1–3 All these drugs have contributed to improve the clinical status together with a more lenient control of glucose metabolism. 4 This is another crucial point to take into account in diabetic patients, especially if elderly, with heart failure in whom aggressive glucose control is detrimental for their functional capacity and long-term prognosis. 5

IRCCS San Raffaele - Ricerca corrente Ministero della Salute 2018.

Conflict of interest : none declared. The authors didn’t receive any financial support in terms of honorarium by Servier for the supplement articles.

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Heart Failure Case Studies

• First Online: 30 March 2023

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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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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 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.

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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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Semaglutide Treatment Effect in People With Obesity and Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus - STEP-HFpEF DM

Contribution to literature:.

The STEP-HFpEF DM trial showed that among obese patients with HFpEF and type 2 DM, once weekly subcutaneous semaglutide was superior to placebo in improving body weight and patient-oriented QoL outcomes at 52 weeks.

Description:

The goal of the trial was to compare the safety and efficacy of semaglutide among patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (DM).

Study Design

Patients were randomized in a 1:1 fashion to once weekly subcutaneous semaglutide (n = 310) or matching placebo (n = 306) for 52 weeks. Semaglutide treatment was initiated at a dose of 0.25 mg once weekly for the first 4 weeks, and the dose was escalated every 4 weeks with the aim of reaching the maintenance dose of 2.4 mg by week 16.

• Total randomized participants: 616
• Median duration of follow-up: 52 weeks
• Median patient age: 69 years
• Percentage female: 44%

Inclusion criteria:

• Left ventricular ejection fraction (LVEF) ≥45%, New York Heart Association (NYHA) functional class II–IV, Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) <90 points, 6-minute walk distance (6MWD) ≥100 m, and ≥1 of the following:
• Elevated LV filling pressures (invasively measured)
• Elevated natriuretic peptide levels and structural echocardiographic abnormalities
• HF hospitalization (previous 12 months) and ongoing requirement for diuretics and/or structural echocardiographic abnormalities
• Type 2 DM diagnosed ≥90 days prior to screening with glycated hemoglobin (HbA 1c ) ≤10%

Exclusion criteria:

• Prior/planned bariatric surgery
• Recent self-reported weight change >5 kg (>11 lbs)
• Recent adverse cardiovascular event or HF hospitalization
• Systolic blood pressure >160 mm Hg at screening
• History of type 1 DM
• Recent glucagon-like peptide-1 (GLP-1) receptor agonist use
• Uncontrolled diabetic retinopathy

Other salient features/characteristics:

• White race: 84%
• Median body weight: 103 kg
• Median body mass index (BMI): 37 kg/m 2
• Atrial fibrillation at baseline: 39%
• Median baseline NT-pro–B-type natriuretic peptide (NT-proBNP): 493 pg/mL
• Baseline medications: diuretic: 81%, mineralocorticoid receptor antagonist: 33%, sodium–glucose cotransporter 2 (SGLT2) inhibitor: 33%

Principal Findings:

The co-primary endpoints for semaglutide vs. placebo from baseline to week 52:

• Change in KCCQ-CSS: 13.7 vs. 6.4 (p < 0.001)
• % change in body weight: -9.8% vs. -3.4% (p < 0.001)

Change in body weight was higher among patients not on SGLT2 inhibitors vs. those on it at baseline (-7.2% vs. -4.7%, p for interaction = 0.04).

Key secondary outcomes for semaglutide vs. placebo:

• Change in 6MWD from baseline to week 52: 12.7 vs. -1.6 m (p = 0.008)
• Hierarchical composite endpoint (proportion of wins): 58.7% vs. 36.8% (p < 0.001)
• Change in HbA 1c from baseline to week 52: -0.7 vs. 0.1 (p < 0.05)
• Percentage reduction from baseline to week 52 in NT-proBNP: -23.2 vs. -4.6 (p < 0.05)
• Time to first HF event: 7 vs. 18 (hazard ratio 0.40, 95% confidence interval 0.15-0.92)
• All-cause mortality: 1.9% vs. 3.3% (p > 0.05)

Interpretation:

The results of this trial show that among obese patients with HFpEF and type 2 DM, once weekly subcutaneous semaglutide was superior to placebo in improving body weight (~6.4% greater weight loss) and patient-oriented quality of life (QoL) outcomes including KCCQ-CSS and 6MWD at 52 weeks. The trial was underpowered for clinical events, although reductions in HF events were noted. These are landmark findings and mirror similar findings in the STEP-HFpEF trial, which included patients with and without DM. Taken together, they support a larger outcomes trial to study the effect of GLP-1 receptor agonist among patients with HFpEF and obesity.

Interestingly, weight loss in this trial was lower compared with STEP-HFpEF (10.7% vs. 6.4%). Although it is hard to directly compare across trials, it is possible that this difference was driven by a difference in SGLT2 inhibitor use between the trials (3.6% in STEP-HFpEF vs. 33% in the current trial); there was also evidence of effect modification by baseline SGLT2 inhibitor use in the current trial, such that a larger benefit was noted among those who were not on it at baseline. That said, even among patients who were on SGLT2 inhibitors at baseline (Class 2a recommendation), a benefit with GLP-1 receptor agonists was observed. It is still somewhat unclear if the improvements in HF-related QoL measures were driven by weight loss (suggesting that other weight loss measures could be considered and potentially beneficial) or independent of this, but increasingly likely that both mechanisms are involved.

References:

Kosiborod MN, Petrie MC, Borlaug BA, et al., on behalf of the STEP-HFpEF DM Trial Committees and Investigators. Semaglutide in Patients With Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med 2024;Apr 6:[Epub ahead of print] .

Presented by Dr. Mikhail Kosiborod at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 6, 2024.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies

Keywords: ACC24, ACC Annual Scientific Session, Diabetes Mellitus, Type 2, Glucagon-Like Peptide-1 Receptor, Heart Failure, Preserved Ejection Fraction, Novel Agents, Obesity

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Case Study: Acute Heart Failure in a 20-year-old Patient

At Piedmont Heart’s Napa Valley Cardiology Conference, Dr. David Dean presents a challenging case of acute heart failure in a 20-year-old patient. Hear Piedmont’s unusual approach to therapy and tips for success from Dr. Dean, surgical director of Piedmont’s Samsky Advanced Heart Failure Center.

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Open Access

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.

• PPT PowerPoint slide
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• TIFF original image

https://doi.org/10.1371/journal.pone.0181001.t001

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.

https://doi.org/10.1371/journal.pone.0181001.t003

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.

https://doi.org/10.1371/journal.pone.0181001.g002

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.

https://doi.org/10.1371/journal.pone.0181001.g003

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

• 1. WHO. Fact sheet on CVDs. Global Hearts. World Health Organization. 2016.
• 2. Al-Shifa IH. Cardiac Diseases‎ in Pakistan [Internet]. 2016 [cited 15 Jun 2017]. http://www.shifa.com.pk/chronic-disease-pakistan/
• View Article
• PubMed/NCBI
• Google Scholar
• 6. Collett D. Modelling Survival Data in Medical Research. 2nd ed. Taylor & Francis; 2003.
• 8. Gillespie B. Checking Assumptions in the Cox Proportional Hazards Regression Model. Midwest SAS Users Group (MWSUG). 2006.
• 11. Efron B, Tibshirani RJ. An Introduction to the Bootstrap. Chapman and Hall, New York; 1993.
• 15. Yang D. Build Prognostic Nomograms for Risk Assessment Using SAS. Proceedings of SAS Global Forum 2013. 2013.

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A forgotten diagnosis in right heart failure: A case report and literature review

Azin alizadehasl.

1 Cardio‐Oncology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran Iran

Bahar Galeshi

2 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran Iran

Mehdi Peighambari

3 Heart Valve Disease Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran Iran

Hamidreza Pouraliakbar

Maryam moradian, arash hashemi.

4 Erfan General Hospital, Tehran Iran

Associated Data

All data relevant to the study are included in the article or uploaded as supplementary information.

Carcinoid heart disease is a well‐known complication of carcinoid syndrome that affects morbidity and mortality. Carcinoid heart disease may be asymptomatic in the early stages; therefore, patients with carcinoid syndrome should be screened to prevent misdiagnosis.

1. INTRODUCTION

Neuroendocrine neoplasms, albeit rare, can beget carcinoid tumors and carcinoid heart disease, with the latter considered a prominent etiology in the field of intrinsic right heart valve disorders, leading to right heart failure and considerable morbidity and mortality. So clinicians need to pay heed to its appropriate diagnosis and prevention.

Neuroendocrine neoplasia constitutes infrequent neoplasms that mostly originate from the gastrointestinal tract. They are reported in 2.5‐5 persons per 100 000 people. 1 The secretion of vasoactive substances by these tumors is responsible for carcinoid syndrome. 2 Carcinoid tumors usually develop gradually, over years, and are likely to show few or no symptoms until they are bulky enough to be symptomatic or have metastasized, mostly to the liver, followed by the skeletal and pulmonary systems. 1 , 3

One of the common complications of carcinoid syndrome is cardiac involvement due to the direct action of vasoactive substances. 2 Carcinoid syndrome can occur in up to 60% of cases during the course of the disease, but carcinoid heart disease (CaHD) can be the first manifestation in approximately 20% of patients. 3 , 4

As cardiac manifestations are associated with a poor long‐term medical prospect and mortality, 3 , 5 the detection of cardiac disease in its early stages has a significant value. Cardiac surgeries such as valve replacement, if performed at the optimal time, significantly contribute to the treatment of symptomatic patients and the improvement of their quality of life. 6

Herein, we describe a patient with CaHD and review the salient practical aspects of carcinoid syndrome and cardiac involvement and introduce a real case referred to our clinic.

2. CASE PRESENTATION

A 75‐year‐old woman was referred for the first time to our cardio‐oncology clinic with the chief complaints of progressive dyspnea, fatigue, peripheral edema, and intermittent palpitation. The patient's medical records, which we reviewed after receiving her informed consent, revealed a previous diagnosis of gastrointestinal neuroendocrine neoplasia (midgut carcinoids) with liver metastasis based on ultrasound imaging and endoscopy 4 years earlier. Since surgery was not suitable for her, treatment was done mostly with the aid of alkalizing agents. With a diagnosis of heart failure, she was also placed on cardiac medications, including aspirin, atorvastatin, losartan, MetoHEXAL, and furosemide, but without regular follow‐ups. Also, remarkable in her past medical history was long‐term hypertension. On presentation to our clinic, a physical examination showed a heart rate of around 80 beats/min, an arterial blood pressure of about 140/75 mm Hg, diminished breath sounds over the right lower lung field, and a normal jugular venous pressure. Cardiac auscultation revealed normal first and second heart sounds and a grade II/VI systolic ejection murmur along the left sternal border. Additionally, lower limb edema was apparent without cyanosis.

The patient had undergone 2D transthoracic echocardiography (TTE) in the past, but its results were not available; consequently, the first step in our clinic saw her undergo a comprehensive 2D TTE examination. The findings were normal left ventricular size with mild systolic dysfunction and diastolic dysfunction; severe right atrial (RA) and right ventricular (RV) enlargement with RV dysfunction; a thickened, retracted, and semi‐mobile tricuspid valve; severe free tricuspid regurgitation caused by the absence of leaflet cooptation; and no valvular stenosis. The assessment of the pulmonary valve also showed thickened, malcoapted valves with severe insufficiency, but without stenosis. Moreover, the left heart valves were mildly thickened, most probably in consequence of aging.

The findings led to a diagnosis of CaHD for the patient. Her dyspnea was mostly related to hypertensive cardiomyopathy, diastolic dysfunction, anemia, and low cardiac output due to RV failure. Her other symptoms could be explained by right heart failure. For the assessment of palpitation, 48‐hour Holter monitoring was performed, which revealed frequent premature atrial and ventricular contractions.

The patient's electrolyte disturbances were corrected through biochemical tests. Further, the medications were adjusted taking into account her tolerance under close monitoring in serial follow‐ups via physical examinations concerning symptoms, the severity of the lower leg edema, blood pressure, heart rate, and laboratory data. The serial follow‐ups were done initially every other week for 1 month for medication adjustments. Thereafter, she was visited 3 months later for symptom evaluation, laboratory tests, and TTE, all of which demonstrated clinical and paraclinical improvements in the signs and symptoms of heart failure. Three months afterward, the patient referred to our clinic for the final follow‐up, which once again confirmed the gradual improvement in her symptoms.

Our case is an instance of a patient whose cardiac symptoms were diagnosed as merely heart failure and, thus, mismanaged. Her overall condition and disease severity rendered her unsuitable for surgery.

3. DISCUSSION

Carcinoid disease is a paraneoplastic syndrome in consequence of the secretion of vasoactive hormones by carcinoid tumors (Figure  1 ). 2 Carcinoid tumors could be discovered anywhere in the body, but a digestive and then pulmonary origin is more common. 1 Chiefly, the tumors arise from the small intestine, commonly in the ileum, and release various kinds of vasoactive chemicals such as serotonin, 5‐hydroxytryptamine (5‐HT), 5‐hydroxytryptophan (5‐HTP), histamine, tachykinins, bradykinins, and prostaglandins into the circulatory system. 2

Carcinoid syndrome and its complications

Carcinoid tumors usually develop gradually, over years. They tend to exhibit few or no symptoms until they are large enough or have metastasized. The metastasis is predominantly to the liver, where the chemicals secreted by the tumors are usually deactivated; otherwise, they reach the systemic circulation and give rise to the clinical manifestations of carcinoid syndrome. 1 , 3 Indeed, between 30% and 40% of patients with carcinoid tumors present with features of carcinoid syndrome. 2 Nonetheless, about 5% of patients, mainly those with primary ovarian or pulmonary tumors or some cases of midgut tumors with retroperitoneal metastases, might show carcinoid symptoms in the absence of liver metastases. 1 , 7 Once large volumes of vasoactive substances reach the right side of the heart, CaHD will appear. Generally, the left side of the heart is spared because these substances are metabolized by the lungs. 2 , 3 First described in 1954, 7 CaHD is expected in more than 50% of affected patients 1 , 8 or even up to 70% of cases 7 in different stages of its severity. 1 , 8 A small male predominance (60%) has been described, and a mean age of 56‐63 years at the time of diagnosis has been reported. 8 Cardiac disease may be detected as an initial presentation of carcinoid syndrome, a well‐known complication that decreases patient survival and causes major morbidity and mortality without therapeutic options. 2 , 8 , 9 Recent decades have, however, witnessed an increase in the survival of patients with CaHD, probably thanks to advances in diagnostic imaging technologies, therapies, cardiac surgeries, and perioperative care. 1

The pathogenesis of CaHD is complex and has yet to be elucidated; nevertheless, the 5‐HT receptors are known to play a fundamental role. These receptors, predominantly the 5‐HT2B subtype, are mostly manifested on cardiac valves. The activation of the 5‐HT receptors can trigger the mitogenesis of fibroblasts and smooth muscle cells, the release of inflammatory cytokines, and the upregulation of the transforming growth factor beta‐1. All these changes lead to the deposition of plaque‐like substances on the endocardial surfaces of the valve leaflets, the subvalvular apparatus (chordae and papillary muscles), the chambers, and occasionally the intima of the pulmonary arteries, the aorta, and the venae cavae. 1 Plaque formation, in turn, sets in motion annular restriction and leaflet thickening, with the resultant significant degenerative changes in the valvular apparatus begetting the severe retraction and non‐coaptation of the valve leaflets. 10 These structural and valvular lesions ultimately bring about right‐sided heart failure. Notably, what differentiates CaHD from the other etiologies of heart failure is a history of flushing, diarrhea, and pulmonary symptoms. 10 , 11 Besides valvular involvement, coronary artery vasospasm is also associated with CaHD and usually presents in patients with a history of nonocclusive coronary artery disease. 3 In the presence of ischemic heart disease, CaHD can lead to coronary artery vasospasm, angina, and in‐stent thrombosis. 4 Arrhythmias, albeit infrequent, might be secondary to increased sympathetic hyperactivity caused by vasoactive chemicals. 3 Atrial and ventricular arrhythmias such as atrial fibrillation, ventricular tachycardia, ventricular fibrillation, and cardiac arrest have also been reported. 4 Infrequently, in about 4% of patients, 1 an isolated intracardiac mass may be a manifestation of CaHD without any valvular involvement. 1 , 4 These well‐defined, homogeneous, and non‐infiltrative masses are mostly found on either ventricle (including the ventricular septum) during echocardiography.

Carcinoid metastasis to cardiac structures can either be asymptomatic and present as a solitary mass or cause ventricular outflow tract obstruction. 3 Heart failure owing to pericardial disease and constrictive pericarditis is a rare manifestation of the disease that may present without an obvious valvular disease. 4

3.1. Clinical features of patients with CaHD

The clinical manifestations of CaHD are often unremarkable in the early stages. Tricuspid and pulmonary valve diseases, even in the advanced stages of involvement, may remain asymptomatic for a long time, which can be explained by the low pressure of the pulmonary circulation. Approximately, 57% of patients with moderate‐to‐severe tricuspid insufficiency are either asymptomatic or mildly symptomatic, 2 , 3 , 12 which likely postpones the detection of carcinoid heart involvement without echocardiographic screening. High clinical suspicion and regular follow‐ups are, therefore, needed to establish a timely diagnosis. 3 , 12 Primary symptoms usually consist of exertional fatigue and dyspnea. Concurrently with tumor progression and increased levels of serotonin, progressive right‐sided heart failure, accompanied by symptom exacerbation, is likely to appear. 12 The main findings on physical examinations include edema and elevated jugular venous pressure. With severe tricuspid insufficiency, the V‐wave may be prominent in the jugular venous pulse and a palpable RV impulse might be detected. Additionally, murmurs of tricuspid and pulmonic valve regurgitation may be audible, even though auscultatory findings are mostly negligible due to low‐pressure resistance in the right circulation. Another clinical feature might be systolic murmurs of pulmonic stenosis. In rare instances of left‐sided disease, it may be possible to auscultate murmurs of mitral and aortic regurgitation. It is also worthy of special note that patients may show central cyanosis in the presence of right‐to‐left shunts. 4 , 10

3.1.1. Imaging

In the primary evaluation of patients with CaHD, the modality of choice is 2D echocardiography in that it can reveal thickness and retraction in the valve leaflets in a semi‐open position with reduced mobility, annular constriction, thickness and fusion in the subvalvular apparatus, and finally regurgitation and /or stenosis of various degrees. 1 , 10 , 11 , 12 , 13 Severe tricuspid regurgitation results in RV volume overload and RV/RA dilatation. 8 , 14 , 15 The findings of 2D echocardiography are summarized in Table  1 .

Echocardiographic features of carcinoid heart disease 8 , 9 , 10

In a review of the echocardiographic findings of 74 patients with CaHD, 100% of the study patients exhibited tricuspid regurgitation, 81% pulmonary regurgitation, 53% pulmonic stenosis, and 7% left‐sided involvement mostly due to the presence of patent foramen ovale (87%) or primary lung neuroendocrine neoplasia (13%).

A comparison between 2D TTE and 3D TTE shows that the latter confers some prominent advantages. The 3D modality allows for a detailed assessment of valvular involvement and the surrounding structures and a more accurate evaluation of myocardial masses in cases of direct metastasis. 16 According to an expert statement by the American College of Cardiology (ACC) concerning the diagnosis and management of CaHD, an echocardiogram should be obtained in all patients with carcinoid syndrome and high suspicion of CaHD. In patients with established CaHD, echocardiography should be repeated every 3‐6 months or during alterations in the clinical status. In contrast, the guidelines of the European Neuroendocrine Tumor Society (ENETS) recommend annual TTE assessments among patients with known CaHD. 2 , 16 Although 2D echocardiography offers such distinct advantages as availability, low cost, and lack of radiation, it is not free of limitations and other modalities like cardiac magnetic resonance imaging or computed tomography (CT) could be helpful in these areas. Cardiac magnetic resonance imaging allows for the accurate assessment of chamber size and regurgitation volume, the precise evaluation of valvular dysfunction, and the identification of the infrequent metastases of neuroendocrine neoplasms to the myocardium and the extracardiac structures. Cardiovascular CT findings are deemed exceedingly useful in operative planning inasmuch as they confer an accurate assessment of chamber size, regurgitation volume, and valvular dysfunction severity (Figure  2 ). 16 Still, it should be borne in mind that overt CaHD may be diagnosed easily by 2D echocardiography, but the detection of the disease in its early stages might pose a formidable challenge.

Carcinoid heart disease. A, TTE in the 4‐chamber view shows RV and RA enlargement with thickened, retracted anterior and septal TV leaflets, leading to the malcoaptation of the TV leaflets. B, RV‐inflow tract view in TTE shows thickened and shortened anterior and posterior leaflets on TV. C, Color Doppler study shows severe free tricuspid regurgitation. D, Doppler profiles shows classical “dagger‐shaped” and low‐pressure TR. E, Parasternal short‐axis view shows thickened, retracted TV leaflets. F, Doppler profile shows severe PI in color Doppler study with short PHT of PI. G, Three‐dimensional TEE shows thickened and malcoapted TV leaflets with a fixed systolic defect in systole. H, Cardiac MRI shows carcinoid involvement of TV leaflets. I, Multiple liver metastases of gastrointestinal tumors are visualized herein. TTE, Transthoracic echocardiography; RV, Right ventricle; RA, Right atrium; TV, Tricuspid valve; TR, Tricuspid regurgitation; PV, Pulmonary valve, PI, Pulmonary insufficiency; PHT, Pressure half‐time; MRI, Magnetic resonance imaging

The accuracy of echocardiography as a screening tool can be enhanced through the use of sensitive and specific biochemical markers associated with the presence and severity of cardiac involvement. Among these useful biomarkers is N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), which is significantly raised in patients with CaHD. This elevation is correlated with disease progression, symptomatic status, and overall survival. An evaluation of NT‐proBNP with a cutoff level of 260 pg/mL is recommended as a screening biomarker with 92% sensitivity, 91% specificity, 98% negative predictive value, and 71% positive predictive value.

The plasma or urinary level of 5‐hydroxyindoleacetic acid (5‐HIAA), which is a metabolite of serotonin, is higher in cardiac involvement, with an elevated level of this metabolite in excess of 300 mmol/24 h being associated with a two‐ to threefold increased risk of the progression of CaHD. 1 , 9

3.1.2. Treatment

The early detection and, thus, timely treatment of CaHD may prevent right heart failure and improve overall survival. The management of these patients is complex and calls for a multidisciplinary approach via a close collaboration between oncologists, cardiologists with expertise in the field of CaHD, and cardiac surgeons. The final goal is to delay the progression of the disease. As the rate of progression is not predictable, regular follow‐ups and intensive monitoring are also required to detect cardiac involvement in the early stages and to determine the timing of surgery before the advanced disease. 9 , 10 , 11 The treatment of cardiac problems in carcinoid syndrome is based not only on the management of volume status and heart failure symptoms but also on the treatment of neuroendocrine neoplasia itself and the reduction in the production of related hormones, as well as ultimately, heart valve surgery. 17 Volume management is necessary, and diuretics (most commonly loop diuretics with aldosterone antagonists or thiazide, if needed) together with fluid and salt restriction are advised. 4 , 18 Nonetheless, caution should be exercised to avoid intravascular depletion in patients with CaHD regardless of the severity of RV dilation or failure because it results in low cardiac output and the manifestation of its symptoms, including light‐headedness, syncope, and fatigue. Other conventional heart failure medications like beta‐blockers, angiotensin‐converting enzyme inhibitors, and angiotensin receptor blockers may be prescribed in some cases, but their efficacy still requires further research.

All of these medications are merely palliative and cannot prevent the progression of the underlying carcinoid syndrome or cardiac involvement. 4 The pharmacological treatment of CaHD is largely allied to the management of the levels of vasoactive hormones by somatostatin analogs. These medications, including octreotide and lanreotide, are somatostatin receptor inhibitors and decrease the secretion of serotonin and its metabolites (eg, 5‐HIAA), hence their value in the control of symptoms.

For patients who are refractory to somatostatin analogs, the new strategy, incorporating the use of everolimus, interferon‐alpha, peptide‐receptor radionuclide therapy, and telotristat etiprate, has shown great promise. 3 , 4 , 9 , 10 Another therapeutic option is the prescription of bosentan, which is a dual endothelin receptor antagonist, for the prevention of valvular and mural fibrosis expansion. 10 The surgical resection of the primary tumors and hepatic metastases seems to decrease the risk of cardiac progression. In the more extensive disease, hepatic intra‐arterial therapies such as embolization can be performed alternatively. Be that as it may, the efficacy of such therapies in stymying the progression of the disease is limited. 9 , 10

The effective management of a patient with CaHD is valve surgery in optimal time by an experienced cardiac surgeon aided by a multidisciplinary team with a view to minimizing the adverse effects of the disease and improving the patient's quality of life. What, however, constitutes the appropriate time for the surgical intervention is currently far from clear. There are different scoring systems, principally based on the tricuspid involvement, but the current guidelines generally recommend valve surgery in the presence of severe symptoms or severe valvular disease or progressive asymptomatic RV dysfunction and dilatation. 4 , 9 , 10 Some investigators have advised cardiac surgery in groups of patients who have controlled baseline carcinoid tumors, with at least 12 months of anticipated postoperative survival from their neuroendocrine neoplasia. 8 Limited evidence is available in favor of surgery in asymptomatic patients. Indeed, the results of the surgical intervention are not conclusive in asymptomatic patients. 9 , 10 Møller and colleagues reported a high perioperative survival rate in the early intervention in asymptomatic or mildly symptomatic patients when compared with severely symptomatic patients. 19

Valve replacement is more common, although extensive fibrotic changes render repair impracticable in most cases. In stenotic lesions not amenable to valve surgery, balloon valvuloplasty is an alternative approach; nevertheless, short‐term hemodynamic and functional benefits and disease relapse diminish the value of this procedure. A controversial topic in the field of valve surgery is the selection of valve prostheses. On the one hand, there is concern regarding bioprosthetic valve degeneration 10 , 12 even as early as 3 months after implantation because of the intractably high levels of the vasoactive products that induce carcinoid plaque reformation. 1 , 12 On the other hand, mechanical prosthetic valves need lifelong anticoagulation therapy in patients who are already prone to bleeding due to hepatic dysfunction. 1 , 8 , 10 The decision‐making process for the selection of the appropriate type of valve prosthesis is complex and should be individualized based on patient risk assessment. The advantages and disadvantages in this regard, summarized in Table  2 , should be explained in detail to the patient as a part of the decision‐making process. The new generation of prosthetic valves with more durability may offer the hope of a more successful rate of valve surgery with less recurrence. Postoperative management should be aimed at maintaining the control of hormone levels and preventing the recurrence of the disease. 12 During valve surgery, patent foramen ovale should be closed. 8

Advantages and disadvantages of valvular prostheses in carcinoid heart disease 11

4. CONCLUSIONS

Carcinoid syndrome presents as a paraneoplastic symptom of rare neuroendocrine neoplasia; however, a well‐recognized complication of this syndrome, cardiac involvement, exerts a significant impact on morbidity and mortality. In patients with CaHD, the involvement of right heart valves is more frequent. The treatment of CaHD requires a multidisciplinary approach. Echocardiographic parameters, in conjunction with other imaging modalities and laboratory tests, can assist in determining the optimal time for surgery.

CONFLICT OF INTEREST

The Authors have no conflict of interest to declare.

AUTHORS' CONTRIBUTION

AA, GB, and PM: conceptualized and designed the study. AA, GB: involved in literature review and manuscript writing. All the authors have discussed and interpreted the data and commented on the manuscript.

INFORMED CONSENT

Written informed consent was obtained from the patient for publication of this manuscript and any accompanying image.

Alizadehasl A, Galeshi B, Peighambari M, Pouraliakbar H, Moradian M, Hashemi A. A forgotten diagnosis in right heart failure: A case report and literature review . Clin Case Rep . 2021; 9 :2040–2047. 10.1002/ccr3.3938 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]

DATA AVAILABILITY STATEMENT

• Open access
• Published: 11 April 2024

Association between dietary selenium and zinc intake and risk of dilated cardiomyopathy in children: a case-control study

• Maryam Aryafar 1 ,
• Mohammad Mahdavi 1 ,
• Hossein Shahzadi 1 ,
• Yeganeh Rajabpour Ranjbar 2 ,
• Mohammad Hassan Sohouli 3 ,
• Sina Afzal 4 ,
• Asal Neshatbini Tehrani 5 , 6 ,
• Danial Fotros 2 &
• Ghazal Daftari 7 , 8  

BMC Pediatrics volume  24 , Article number:  251 ( 2024 ) Cite this article

Metrics details

Dilated cardiomyopathy (DCMP) is characterized by the enlargement and weakening of the heart and is a major cause of heart failure in children. Infection and nutritional deficiencies are culprits for DCMP. Zinc is an important nutrient for human health due to its anti-oxidant effect that protects cell against oxidative damage. This case-control study aimed to investigate the relationship between dietary intake of zinc and selenium and the risk of DCMP in pediatric patients.

A total of 36 DCMP patients and 72 matched controls were recruited, and their dietary intakes were assessed via a validated food frequency questionnaire. We used chi-square and sample T-test for qualitative and quantitative variables, respectively. Logistic regression analysis was applied to assess the relationship between selenium and zinc intake with the risk of DCMP.

After fully adjusting for confounding factors, analyses showed that selenium (OR = 0.19, CI = 0.057–0.069, P trend < 0.011) and zinc (OR = 0.12, CI = 0.035–0.046, P trend < 0.002) intake were strongly associated with 81% and 88% lower risk of pediatric DCMP, respectively.

Conclusions

This study highlights the protective role of adequate dietary intake of selenium and zinc in decreasing the risk of DCMP in children. Malnutrition may exacerbate the condition and addressing these micronutrient deficiencies may improve the cardiac function. Further studies are recommended to detect the underlying mechanisms and dietary recommendations for DCMP prevention.

Peer Review reports

Introduction

Dilated cardiomyopathy (DCMP) is a condition characterized by systolic dysfunction and biventricular or left ventricle dilation in the lack of predisposing factors such as coronary artery disease, hypertension or valvular disorders which cause systolic dysfunction [ 1 ]. DCMP usually begins in the left ventricle by thinning and stretching of the heart muscles resulting in enlargement of heart chambers that impairs the normal contraction and blood pumping [ 2 ]. DCMP presents with orthopnea, heart failure, breathlessness, impaired exercise tolerance, poor feeding, fatigue and sweating [ 3 ]. The prevalence of DCMP is estimated from 1:500 to 1:2500 in general population [ 4 , 5 ]. In children, the incidence rate is about 0.57 per 100,000 population annually and is higher in boys than girls [ 6 ]. In children, the common causes of DCMP is idiopathic, neuromuscular disorders such as Becker and Duchen dystrophies, nutritional deficiencies and inflammation [ 7 ]. Paediatric DCMP is observed to occur after influenza, parvo virus B19, coxsackie, herpes, Ebstein Barr, adeno and human immunodeficiency viruses [ 7 ]. Furthermore, taurine, calcium, zinc and selenium depletion decrease the heart contractility and are implicated in DCMP [ 8 ].

Selenium and zinc, micronutrients found in red meat, grains, nuts and sea foods is an indispensable elements in human health [ 9 ]. Selenium in the form of selenocysteine and as the 21st amino acid is incorporated in the selenoproteins, modulating immunologic, cardiovascular and metabolic functions via anti-inflammatory, anti-cancer and anti-oxidant effects [ 10 ]. Also, selenium is crucial for sperm motility and thyroid function [ 11 ]. Gluthatione peroxidases, iodothyronine deiodinases and thioredoxin reductases are anti-oxidant enzymes depending on selenium [ 12 , 13 ]. Zinc is an important element in apoptosis and cellular membrane stability [ 14 ]. In addition, it is a necessary component of enzymes such as angiotensinogen converting enzyme and carbonic anhydrases that are regulators of acid-base balance and fluid homeostasis [ 15 ]. Zinc is a co-factor of different enzymes that contribute to function of anti-oxidant systems. It stabilizes cellular membrane and protects the cells against oxidative conditions. In addition, zinc inhibits pro-oxidant enzymes and decreases reactive oxygen species production in stress conditions [ 16 , 17 , 18 ].

Several studies have demonstrated that selenium deficiency may contribute to cardiovascular disorders such as Keshan disease, which is an endemic DCMP in China [ 19 ]. It is also indicated that zinc deficiency is culprit of cardiac cellular damage and decreased cardiac function [ 20 , 21 ]. It is suggested that high selenium and zinc intake may reduce the risk of cardiovascular incidence and mortality [ 22 ]. Considering previous studies, little is known about the selenium and zinc intake in children with DCMP, thus we aimed to explore the association of dietary intake of selenium and zinc with DCMP risk in children.

Methods and materials

Study population.

In this case-control study, 45 patients within the age range of 2–17 years old who had been diagnosed with idiopathic DCMP for at least 6 months, were recruited from Rajaie cardiovascular, medical and research center during spring and summer of 2022 in Tehran, Iran. Physical exam, electrocardiogram (ECG), clinical history, echocardiography and chest X-ray had been used for diagnosis.

Inclusion criteria were individuals with signs and symptoms of heart failure such as low exercise tolerance, fatigue, edema and shortness of breath. Exclusion criteria were following: having renal failure, diabetes mellitus, malignancies, infectious disease, pregnancy, valvular, rheumatic, hypertensive and congenital heart diseases and also, life expectancy less than 6 months. Among 45 patients that were initially identified, 9 patients were excluded due to the high risk of mortality. Also, 72 controls were matched according to sex and age. The controls were randomly allocated patients admitted to other wards of the same hospital with no history of cardiovascular diseases, confirmed with echocardiography. It is important to mention that when the cases are selected from hospital, controls from hospital are preferred over community-based control selection. The protocol of this study was approved by Rajaie cardiovascular, medical and research center ethics committee (IR.RHC.REC.1401.016). All the parents / legal guardian of participants were informed about the study and signed the written informed consent form.

Dietary intake assessment

A reproducible and valid food frequency questionnaire (FFQ) [ 23 , 24 , 25 ] was used to collect dietary intake. A trained dietician collected the portion size and frequency of food items based on daily, weekly, monthly or yearly intake. The dietary intakes of participants were checked with their parents to reduce the recall bias. We used Nutritionist IV [ 26 ] to analyse the collected data and The United States Department of Agriculture (USDA) Food Composition Table (FCT) to calculate nutrients and energy contents.

Data collection

Socio-demographic and anthropometric information of the participants were collected by a trained interviewer. Body weight was measured to the nearest 100 g while standing on digital scales (Soehnle, Berlin, Germany). Height was calculated by a non-stretch portable meter to the nearest 0.5 cm. Body mass index (BMI) was measured by dividing of weight in kilograms to square of height in meter.

Statistical analysis

After assessing the normality of the variable’s distribution by Kolmogorov-Smirnov test, independent sample T-test was used to compare quantitative variables between the two groups, as Chi-square was also used for qualitative variables. The baseline characteristics were reported as mean ± standard deviation (SD) for quantitative variables, and number for qualitative variables. The association of selenium/zinc with the odds of cardiomyopathy was assessed by applying logistic regression. The analyses were adjusted for probable confounders, including age, sex, BMI, energy, fiber, Na and K. All analyses were performed using statistical package software for social science (SPSS) 22.0 statistical software, and P -value less than 0.05 was considered statistically significant.

Baseline characteristics

The mean ± SD for the age across case and control groups were 9.83 ± 4.55 and 8.7 ± 1.54 years, respectively. There was a significant difference in the distribution of sex between cases and controls ( p  < 0.001), with a higher proportion of males in the control group. However, no significant differences were observed in weight ( p  = 0.208) and BMI ( p  = 0.702) between the two groups (Table  1 ).

Dietary intakes

The dietary intakes of study participants across the case and control groups are presented in Table  2 . Significant differences were found in the intake of protein, carbohydrate, total fiber, fat, cholesterol, sodium, potassium, vitamin A.RE, vitamin C, iron, vitamin D, vitamin E, folate, B12, magnesium, zinc, and selenium between cases and controls ( p  < 0.05 for all). Cases generally exhibited lower intakes of these nutrients compared to controls.

Odds ratios for cardiomyopathy

The odds ratio (ORs) and 95% confidence interval (CIs) for the occurrence of cardiomyopathy based on the tertiles of selenium and zinc intake are reported in Table  3 . In the crude model, selenium and zinc were inversely associated with the lower odds of cardiomyopathy, with an OR of 0.144 and 0.179 for the highest tertile, respectively ( P  < 0.05 for trend). Furthermore, after adjusting for age, sex, BMI, energy, fiber, Na and K (in the fully adjusted model), in the highest versus lowest tertile of selenium and zinc, the lower odds of cardiomyopathy remained significant (OR = 0.198, 95% CI: 0.05–0.69; P value = 0.011 for trend and OR = 0.127, 95% CI: 0.03–0.46; P value = 0.002 for trend, respectively).

The present case-control study demonstrated that lower intake of macronutrients and micronutrients such as selenium and zinc is associated with higher risk of DCMP in children, after fully adjusting of confounding factors such as energy, BMI, age, sex, fiber, Na and K.

In our study, dietary intake of macronutrients was significantly lower in cases than controls. Align with our finding Ocal et al. reported that children with malnutrition exhibit cardiovascular disorder including arrythmia, sudden death, heart failure and dilated cardiomyopathy [ 27 ]. Also, gross examination of the myocardium in malnourished children showed a flabby, pale and thin-walled heart [ 28 ]. Nutritional interventions may improve the quality of life and myocardial function. Failure to thrive is one of the most important problems in children with cardiomyopathy. Adequate intake of macronutrients may improve cardiac function and also, specific micronutrients decrease the myocardial abnormalities that occur in cardiomyopathies and heart failure [ 29 ].

There is a vicious circle between malnutrition and DCMP. Poor nutritional status is a cause of DCMP and on the other hand, DCMP leads to malnutrition through metabolic disturbances, chronic inflammation and gastrointestinal malabsorption [ 30 , 31 , 32 ]. The inflammatory condition in most chronic diseases such as DCMP affects the metabolism and results in reduced cardiac muscle function and mass over time [ 33 ]. Different micronutrients deficiency may cause DCMP. Vema et al. reported a 15-month-old child with DCMP caused by hypocalcemia nutritional rickets that responded to vitamin D and calcium supplementation and systolic function normalized after 3 months [ 34 ].

Consistent with our study, Ripa et al. reported that primary or secondary zinc deficiency may result in DCMP and also, reduced plasma level of zinc is an important prognostic and diagnostic marker for DCMP [ 35 ]. In addition, Topuzoglu et al. demonstrated that patients with DCMP have lower plasma level of zinc compared with healthy controls [ 36 ]. Zinc is an important component of various enzymes such as superoxide dismutase. An impairment in superoxide dismutase function leads to reaction of superoxide anions with hydrogen peroxide and production of hydroxide radicals that induce cell damage. Zinc protects the cells against free radicals and thus decreases the cardiovascular disorders. In DCMP and consequently heart failure, activation of atrial natriuretic peptide (ANP) causes high urinary excretion of zinc, concluding to zinc deficiency and impaired cardiac performance [ 37 ]. On the other hand, Chou et al. did not find any association between patients with DCMP and control group [ 38 ]. The differences in reports may be due to sample size, dietary food intake and methodology.

Another micronutrient that is protective in cardiovascular diseases is selenium. Dasgupta et al. reported a 14 years old boy with severe malnutrition, selenium deficiency and heart failure that has been treated with selenium replacement and nutritional support and become completely asymptomatic after four weeks [ 33 ]. In line with our study, Khater et al. demonstrated that pediatric patients with DCMP have reduced plasma level of selenium and this element can prevent myocardial damage [ 39 ]. Frustaci et al. indicated that in patients with intestinal malabsorption, a reversible selenium and zinc DCMP may occur oxidative damages to cell membrane, increased cell autophagy and decreased anti-oxidant activity [ 40 ]. Furthermore, Basil et al. reported that selenium level is significantly lower in patients with DCMP in comparison with control group [ 41 ]. In contrast to our study, Cunha et al. investigated that there is no difference between selenium level in patients with DCMP and control group [ 42 ]. It may be due to different food pattern and sample size. Selenium is a crucial element in inflammation and immunity and improves antioxidant reserve and suppresses production of tumor necrosis factor alfa and interleukins. Selenium deficiency may also play a role in myocardial damage and recovery.

Current study has some strengths including the analysis of various macro and micronutrients and also adjusting the confounding factors to improve the reliability of the study. There are some limitations, due to case-control nature of the study we could not establish a causative relationship between selenium and zinc intake with DCMP and the possibility of recall bias is another issue to consider.

In conclusion, current study concluded that there is an inverse association between macronutrients, selenium and zinc intake with the risk of pediatric DCMP. Further studies are needed to evaluate the amount of selenium and zinc intake to prevent DCMP.

Data availability

The datasets examined in the current study are available from the corresponding author on.

reasonable request.

Abbreviations

dilated cardiomyopathy

electrocardiogram

food frequency questionnaire

the United States department of agriculture

food composition table

body mass index

standard deviation

statistical package software for social science

confidence interval

saturated fatty acid

retinol equivalent

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Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences Tehran, Tehran, Iran

Maryam Aryafar, Mohammad Mahdavi & Hossein Shahzadi

Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, Research Institute, National Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Yeganeh Rajabpour Ranjbar & Danial Fotros

Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Mohammad Hassan Sohouli

Department of Orthopedic and Trauma Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Asal Neshatbini Tehrani

Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Ghazal Daftari

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Conceptualization, M.A; Formal analysis, M.S and D.F; Methodology, M.M, H.S and Y.R; Project administration, M.A and G.D; Writing – original draft, S.A and A.N.T; Writing – review & editing, G.D and S.A. All authors read and approved.

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Aryafar, M., Mahdavi, M., Shahzadi, H. et al. Association between dietary selenium and zinc intake and risk of dilated cardiomyopathy in children: a case-control study. BMC Pediatr 24 , 251 (2024). https://doi.org/10.1186/s12887-024-04706-1

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DOI : https://doi.org/10.1186/s12887-024-04706-1

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New study shows effect of socio-economic factors—housing, food, neighborhood—to predict diabetic patients’ risk of heart failure

A recent study by  Case Western Reserve University  used national data from U.S. military veterans with diabetes to validate and modify a widely accepted model used to predict the risk of heart failure in diabetic patients.

The model, called the WATCH-DM score, is used to predict the likelihood of heart failure in diabetes patients within five years.

But because it overlooks the influence of social determinants of health‚ such as housing, food and a patient’s neighborhood, the researchers used a social deprivation index (SDI), a multi-component summary score, to adjust the WATCH-DM score. 

The SDI, introduced by the  Robert Graham Center,  a group of clinical researchers, can quantify the level of disadvantage in particular areas using food, housing, transportation and community conditions. Prior research demonstrated this score is directly proportional to the level of health disparities observed in communities.

The study identified about 1 million U.S. veterans with type 2 diabetes without heart failure treated as outpatients at Veterans Affairs medical sites nationally in 2010.

Researchers used patient zip codes to obtain their SDI, which was then entered into the risk calculator to determine how likely they would be hospitalized for heart failure within five years.   

While the hospitalization rate for heart failure for the whole cohort of more than 1 million patients was 5.39%, this incidence varied from 3% (in the least socially deprived) to 11% (in the most deprived). 

Researchers found that, depending on the patients’ other clinical information, adding the SDI into the risk-prediction model could even double the probability of that patient developing heart failure in the next five years.

The team of investigators then optimized the WATCH-DM score for each SDI group using a statistical correction factor and improved its predictive accuracy across the whole range of the social determinants of health. 

“We found that adding the SDI enhanced the WATCH-DM score’s ability to forecast risk,” said Salil Deo, an associate professor in the  Department of Surgery at Case Western Reserve School of Medicine, who led the study. “These results highlight the necessity of including social determinants of health in any future clinical risk prediction algorithms. This will increase their accuracy, which will benefit patients by improving their health outcomes.”

View the calculator. 

“We hope our study encourages healthcare providers to adopt a wholistic approach when treating patients in the future,” Deo said. “Understanding and quantifying social inequity is likely the first step we can take toward trying to ensure that it does not affect the health of our patients.” 

For more information, contact Patty Zamora at [email protected] .

Wegovy Helps Those With Both Diabetes, Heart Failure: Study

By Robin Foster HealthDay Reporter

TUESDAY, April 9, 2024 (HealthDay News) -- For people struggling with both diabetes and a common type of heart failure, the weight-loss drug Wegovy may do more for their health than help them shed pounds, new research suggests.

In the study, published Saturday in the New England Journal of Medicine , researchers reported that the drug helped people with type 2 diabetes who also had obesity-related "heart failure with preserved ejection-fraction," on several fronts.

This condition happens when the heart pumps normally, but the organ is too stiff to fill properly.

“I think the answer from the trial clearly suggests that, while weight loss is likely an important factor, it cannot explain everything,” study co-author Dr. Mikhail Kosiborod , a cardiologist and vice president of research at St. Luke’s Health System in Kansas City, Mo., told CNN .

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“I think that’s incredibly exciting because first of all, these patients are really difficult to treat and there are a lot more of them every day,” Kosiborod said. “And until recently, we had very little to offer them, so if we know it actually modifies the disease process, we have something really effective -- and by the way, really well-tolerated as well -- and that’s, of course, great news for patients and great news for doctors taking care of patients.”

People with obesity-related heart failure tend to tire easily and have trouble breathing, and those who also have type 2 diabetes have a more severe form than those who don’t have the blood sugar disease.

The researchers who conducted this latest study -- which was funded by drug maker Novo Nordisk -- also published a study last fall that found that Wegovy delivered significant benefits to people without diabetes who had obesity-related heart failure. However, the team wanted to see whether the drug would work as well in people who also had diabetes.

Wegovy was first approved in 2021 to treat obesity. Just last month, the U.S. Food and Drug Administration also approved Wegovy to reduce the risk of cardiovascular death, heart attack and stroke in obese/overweight adults with heart disease. This latest study offers up fresh evidence that Wegovy’s benefits extend to people with diabetes.

For the study, the researchers randomly assigned 616 people who had type 2 diabetes and heart failure with preserved ejection-fraction into two groups. The participants came from 108 sites in 16 countries, and all had a body-mass index of 30 or more. One group got Wegovy, and the other group got a placebo.

The participants who got Wegovy started at a lower dose and worked their way to a 2.4 milligram dose once a week. Researchers followed both groups for a year.

Patients who got Wegovy had much better outcomes, with more weight loss and a bigger reduction in heart failure-related symptoms and physical limitations. They also could walk farther over the course of six minutes   and showed improvements in biomarkers for inflammation.

There were 55 serious adverse events reported in the group that took Wegovy and 88 in the placebo group. Six people died in the Wegovy group, compared with 10 in the placebo group. One death in the Wegovy group and four in the placebo group were related to heart issues.

The findings of this trial, along with the one published last year, suggest Wegovy works for a broad population of people, Kosiborod said.

Kosiborod, who presented the research Saturday at the American College of Cardiology annual meeting in Atlanta, added that he thinks the study opens up the possibility of treating heart failure by treating obesity.

“Obesity, it is a lot more than weight. It’s a systemic cardiometabolic condition that causes all kinds of bad things, and treating obesity involves weight loss, but it means a lot more than that,” he said. “We have to target it, and I think future standards of care for this type of heart failure will improve, and without a doubt in my mind, it’s going to include obesity management.”

More information

Drugs.com has more on weight-loss drugs .

SOURCES: New England Journal of Medicine , April 6, 2024; CNN

Copyright © 2024 HealthDay . All rights reserved.

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New study shows effect of socio-economic factors—housing, food, neighborhood—to predict diabetic patients’ risk of heart failure

Case Western Reserve University

Credit: Case Western Reserve University

CLEVELAND—A recent study by  Case Western Reserve University  used national data from U.S. military veterans with diabetes to validate and modify a widely accepted model used to predict the risk of heart failure in diabetic patients.

The model, called the WATCH-DM score, is used to predict the likelihood of heart failure in diabetes patients within five years.

But because it overlooks the influence of social determinants of health‚ such as housing, food and a patient’s neighborhood, the researchers used a social deprivation index (SDI), a multi-component summary score, to adjust the WATCH-DM score. 

The SDI, introduced by the  Robert Graham Center,  a group of clinical researchers, can quantify the level of disadvantage in particular areas using food, housing, transportation and community conditions. Prior research demonstrated this score is directly proportional to the level of health disparities observed in communities.

The study identified about 1 million U.S. veterans with type 2 diabetes without heart failure treated as outpatients at Veterans Affairs medical sites nationally in 2010.

Researchers used patient zip codes to obtain their SDI, which was then entered into the risk calculator to determine how likely they would be hospitalized for heart failure within five years.   

While the hospitalization rate for heart failure for the whole cohort of more than 1 million patients was 5.39%, this incidence varied from 3% (in the least socially deprived) to 11% (in the most deprived). 

Researchers found that, depending on the patients’ other clinical information, adding the SDI into the risk-prediction model could even double the probability of that patient developing heart failure in the next five years.

The team of investigators then optimized the WATCH-DM score for each SDI group using a statistical correction factor and improved its predictive accuracy across the whole range of the social determinants of health. 

“We found that adding the SDI enhanced the WATCH-DM score’s ability to forecast risk,” said Salil Deo, an associate professor in the  Department of Surgery at the Case Western Reserve School of Medicine, who led the study. “ These results highlight the necessity of including social determinants of health in any future clinical risk prediction algorithms. This will increase their accuracy, which will benefit patients by improving their health outcomes.”

This calculator is available to the public from their device for free  here . 

“We hope our study encourages healthcare providers to adopt a wholistic approach when treating patients in the future,” Deo said. “Understanding and quantifying social inequity is likely the first step we can take toward trying to ensure that it does not affect the health of our patients.” 

Case Western Reserve University is one of the country's leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 6,000 undergraduate and 6,300 graduate students comprise our student body. Visit  case.edu  to see how Case Western Reserve thinks beyond the possible.

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