69 year-old Abdur Rehman, a green grocer by profession, visits his doctor because he feels tired, has to take a short break whenever he does physical exercise like lifting sacks of food or shifting bins so leaves the heavy lifting and moving to his son who works with him.. He no longer visits the mosque for his congregational prayers as he feels breathless and tired on the long walk to the mosque. He has not felt any chest pain on exercise or rest. Sleeps using one pillow. His weight has not changed and his appetite is as usual. He has not noticed any swelling of the feet or facial puffiness. His pulse is regular and he does not have any palpitation or syncopal attacks. His urine output is as usual and has not declined nor does he wake up at night to empty the bladder. He is on medication for hypertension (enalapril and a thiazide), Type 2 diabetes (metformin and sitagliptin combination), takes statins for hyperlipidemia and aspirin 75 mg/day. He is regular with his medication.
What are the possibilities for his symptoms?
A. His heart failure has become symptomatic, so check for signs of heart failure; determine what class and stage of heart failure he is in and determine from his previous record what his status was when he came in for his last visit.
Functionally he is in class 2 heart failure as determined by NYHA classification.
Class I – Patients with heart disease without resulting limitation of physical activity. Ordinary physical activity does not cause HF symptoms such as fatigue or dyspnea.
Class II – Patients with heart disease resulting in slight limitation of physical activity. Symptoms of HF develop with ordinary activity but there are no symptoms at rest.
Class III – Patients with heart disease resulting in marked limitation of physical activity. Symptoms of HF develop with less than ordinary physical activity but there are no symptoms at rest.
Class IV – Patients with heart disease resulting in inability to carry on any physical activity without discomfort. Symptoms of HF may occur even at rest.
B. This may be caused by because of worsening of the ischemic heart disease so stage the heart failure.This determines the progression of structural damage and combines the class of heart failure with the risk from structural changes in the heart. The stages in the evolution of HF, as outlined by the American College of Cardiology Foundation/American Heart Association guidelines are as follows:
- Stage A – At high risk for HF but without structural heart disease or symptoms of HF.
- Stage B – Structural heart disease but without signs or symptoms of HF. This stage includes patients in NYHA functional class I with no prior or current symptoms or signs of HF.
- Stage C – Structural heart disease with prior or current symptoms of HF. This stage includes patients in any NYHA functional class (including class I with prior symptoms).
- Stage D – Refractory HF requiring specialized interventions. This stage includes patients in NYHA functional class IV with refractory HF.
This possibility must always be kept in mind. He appears to be in stage C. He needs an ECG at rest, and after exercise, an echocardiogram to look for ventricular wall motion abnormality, dysfunction of the valves. His troponin and other cardiac enzymes need to be checked. Does he warrant an investigation of his cardiac vasculature? Can you reduce his risk by doing a revascularisation procedure?
What is his ejection fraction and if he is in heart failure is he in systolic or diastolic HF?
HF with reduced EF ([HFrEF] left ventricular EF ≤40 percent) is also known as systolic HF or HF due to systolic dysfunction. Most randomized controlled trials for HF have enrolled patients with HFrEF, and therapy with established efficacy is available for HFrEF but not HF with preserved EF (HFpEF).
Heart failure with preserved ejection fraction known as diastolic HF, refers to HF in patients with a left ventricular EF ≥50 percent or >50 percent . Patients with left ventricular EFs between 41 and 49 may be categorized as having “HFpEF, borderline” with characteristics similar to patients with HFpEF.
Diastolic dysfunction can be induced by many of the same conditions that lead to systolic dysfunction. The most common causes are hypertension, ischemic heart disease, diabetes, hypertrophic obstructive cardiomyopathy, and restrictive cardiomyopathy.w
What would you consider potentially diagnostic ECG changes?
- Evidence of ischemic heart disease, such as T wave changes, ST elevation or depression, q waves or other evidence of prior or acute myocardial infarction or ischemia.
- Left ventricular hypertrophy due to hypertension; a pseudoinfarct pattern may also be present representing significant posterior forces of the increased left ventricular mass.
- Low limb lead voltage on the surface ECG with a pseudo-infarction pattern (loss of precordial R wave progression in leads V1-V6) can suggest an infiltrative process such as amyloidosis.
- Low limb lead voltage with precordial criteria for left ventricular hypertrophy is most suggestive of idiopathic dilated cardiomyopathy. A widened QRS complex and/or a left bundle branch block pattern is also consistent with this diagnosis.
- Heart block, that may be complete, and various types of intraventricular conduction defects are observed in patients with cardiac sarcoidosis.
- The presence of a persistent tachycardia such as atrial fibrillation with a rapid ventricular response may result from or lead to HF, since this arrhythmia can cause cardiomyopathy (tachycardia-mediated cardiomyopathy).
On examination of this patient he did not have signs of heart failure like peripheral edema or other evidence of fluid retention like a pleural effusion or ascites. His heart was not clinically enlarged, he had no third or fourth heart sound audible nor was a murmur audible and the liver was not palpable, the lungs were clear to auscultation. So he did not appear to have a worsening in the staging of his heart failure. His ECG, exercise tolerance test, x ray of the chest and echocardiogram were unremarkable. He was in sinus rhythm. His ejection fraction is 58%. So why is he symptomatic?
C. Check his blood pressure several times and ask him to bring a record of his BP readings when he comes to see you 3 days later if he has a BP monitor at home. His BP was 130/80 in the OPD. He was admitted in the high nursing care ward as he lived too far away to get his tests done. He was put on a cardiac monitor and his blood pressure went up to 168/100 during deep sleep around 3am but was normal when he woke up. Hypertension is one of the common modifiable factors in the treatment of heart failure. He needs to have his dose of enalapril increased with the dosage being given at night to achieve peak action at night. He was given enalapril 5 mg with breakfast and 10 mg with dinner. the thiazide was given with breakfast.
HF may be provoked or worsened by drugs, such as calcium channel blockers, particularly verapamil; beta blockers; and nonsteroidal antiinflammatory drugs.
D. Has your patient developed pulmonary hypertension?
Patients with chronic HF often develop secondary pulmonary hypertension, which can contribute to dyspnea as pulmonary pressures rise with exertion. These patients may also complain of substernal chest pressure, typical of angina. In this setting, elevated right ventricular end-diastolic pressure leads to secondary right ventricular subendocardial ischemia. Physical signs of pulmonary hypertension can include increased intensity of P2, a murmur of pulmonary insufficiency, a parasternal lift, and a palpable pulmonic tap
E. Initial blood tests
- A complete blood count, which may suggest concurrent or alternate conditions. Anemia or infection can exacerbate pre-existing HF.
- Serum electrolytes (including calcium and magnesium). Hyponatremia generally indicates severe HF, though it may occasionally result from excessive diuresis.
- Blood urea nitrogen, and creatinine may indicate associated conditions. Renal impairment may be caused by and/or contribute to HF exacerbation. Baseline evaluation of electrolytes and creatinine is also necessary when initiating therapy with diuretics and/or angiotensin converting enzyme inhibitors.
- Liver function tests, which may be affected by hepatic congestion.
- Fasting blood glucose and lipid profile to detect underlying diabetes mellitus and lipid disorders.
- Thyroid stimulating hormone, since hyperthyroidism or hypothyroidism can precipitate HF.
Should his BNP be checked? Probably not if you are sure that his symptoms are from heart failure. BNP — Most dyspneic patients with HF have values above 400 pg/mL, while values below 100 pg/mL have a very high negative predictive value for HF as a cause of dyspnea. In the range between 100 and 400 pg/mL, plasma BNP concentrations are not very sensitive or specific for detecting or excluding HF.
This patient had an Hb level of 11.5gm/dl. His previous record showed an Hb of 12 gm 6 months ago and 13.5 gm 12 months ago. Is the anemia the cause of his symptoms?
In an analysis from the SOLVD trial, 22 percent of patients had a hematocrit ≤39 percent and 4 percent had values below 35 percent . A similar rate of anemia (17 percent) was noted in a population-based cohort of 12,065 patients with newly diagnosed HF . The incidence of anemia appears to increase with worsening functional class. Anemia itself is rarely the cause of heart failure in the absence of structural heart disease. A hemoglobin of less than 5gm/dl may cause heart failure per se but a low hemoglobin can cause high output heart failure in a patient with valvular and other heart failure. However a low hemoglobin can precipitate the symptoms of angina pectoris and worsen heart failure especially from ischemic heart disease.
What anemia is this patient likely to have? The following tests are likely to help you sort out the cause.
- Complete blood count, including red cell indices, reticulocyte count, and evaluation of the peripheral blood smear
- Iron studies (serum iron, transferrin, iron saturation, ferritin)
- Renal function (eg, serum creatinine, creatinine clearance)
- C-reactive protein and erythrocyte sedimentation rate (may be useful if ferritin is borderline to assess for inflammation as a factor)
- Serum levels of vitamin B12 and folate
In addition to his hemoglobin of 11.5gm/dl his serum ferritin level is 41 ng/dl and Tsat is <20%. White cell count and platelets are normal. The reticulocyte count is 2%. (A reticulocyte count determines whether there is decreased RBC production, which is consistent with iron deficiency; increased RBC destruction (hemolysis); or blood loss,) This is suggestive of iron deficiency anemia.
Who is likely to have iron deficiency anemia among male adults? All patients who are found to have microcytic, hypochromic anemia, patients who cannot afford to eat an adequate diet, patients on fad diets or on NSAIDs, people with GERD or epigastric pain or heartburn, the restless legs syndrome may predict iron deficiency among other things, patients with CRF who are on dialysis and erythropoietin but are restricting their diet because of renal failure.
What should we ask about in the history? History of gastrointestinal blood loss, melena, hematemesis, and hematuria, history of multiple blood donations, use of non-steroidal anti-inflammatory drugs (NSAIDS) or anticoagulants, personal or family history of bleeding diathesis, including platelet disorders, von Willebrand disease, hereditary hemorrhagic telangiectasia, personal or family history of colon cancer, or other gastrointestinal disorders, review of the results of prior gastrointestinal evaluations (eg, routine colon cancer screening).
Test the stool for occult blood in adults 50 years of age or older.
If he is positive for occult blood (perhaps even if he is negative) do an upper GI endoscopy. Why is this useful? Important lesions in the upper digestive tract are frequently detected in patients who test positive for fecal occult blood or have iron deficiency anemia. While the presence of symptoms referable to the upper gastrointestinal tract has been associated with the detection of corresponding findings, even in patients without symptoms, the prevalence of lesions in the upper gastrointestinal tract is greater than or equal to that of colonic lesions
Colonoscopy — Because of the high prevalence of colorectal cancer and adenomatous polyps in developed countries, most patients should undergo colonoscopy. Colonoscopy is the preferred modality for evaluating the colon because it can detect a wide range of lesions, including polyps, cancers, and angiodysplasias.
What is virtual colonoscopy and is it useful? Barium enemas and computed tomographic [CT] colonography, also called “virtual colonoscopy; rarely yield equivalent results to actual examinations.
A person can have iron deficiency with or without anemia.
Ferritin levels are used as a surrogate for iron stores and are generally a good measure of storage iron as long as the individual does not have an active inflammatory process or chronic disease (ferritin is an acute phase reactant). For ferritin levels in the range from 20 to 300 ng/mL, there appears to be a direct quantitative relationship between the ferritin concentration and iron stores.
In the pre-anemia stage:
- Low levels of ferritin and serum iron (Fe).
- Increased levels of transferrin (Tf; total iron binding capacity [TIBC]).
- Low percent saturation of transferrin (ie, Fe/TIBC or Fe/Tf, stated as a percent).
- Increased unsaturated iron binding capacity (UIBC = TIBC – Fe).
Iron deficiency in clinical trials was defined as a serum ferritin level <100 mcg/L or a serum ferritin level of 100 to 300 mcg/L if transferrin saturation is <20% (Anker 2009; Ponikowski 2015).
Functional iron deficiency (also referred to as iron-restricted erythropoiesis) occurs in:
- Chronic inflammation. Common causes include infections, malignancies, bariatric surgery (in certain individuals), or chronic medical conditions such as diabetes.
- Use of ESA (erythropoietin stimulating agents)
Uses for oral iron — Oral iron provides an inexpensive and effective means of restoring iron balance in a patient with iron deficiency without complicating comorbid conditions. May be the only form available cheaply to the patient. Uses for oral iron supplements include the following:
- Treatment of iron deficiency anemia
- Treatment of iron deficiency without anemia
- Nutritional support to prevent deficiency
In contrast, oral iron may not be effective for individuals with ongoing blood loss, inflammatory bowel disease or gastric bypass, chronic kidney disease, or those with substantial distress from the side effects of oral iron.
Uses for IV iron — There are a number of settings in which the use of IV iron may be preferable to oral iron
- Patients who cannot (or prefer not to) tolerate the gastrointestinal side effects of oral iron.
- Patients who prefer to replete iron stores in one or two visits rather than over the course of several months.
- Ongoing blood loss that exceeds the capacity of oral iron to meet needs (eg, heavy uterine bleeding, mucosal telangiectasias).
- Anatomic or physiologic condition that interferes with oral iron absorption.
- Coexisting inflammatory state that interferes with iron homeostasis.
Choice of IV preparation — A number of IV iron formulations are available, including ferric carboxymaltose (FCM), ferric gluconate (FG), ferumoxytol, iron sucrose (IS), iron isomaltoside (not available in the United States), and low molecular weight iron dextran (LMW ID). (I have left the links in for further reading.)
FCM dosage. Iron deficiency anemia: IV:
<50 kg: 15 mg/kg on day 1; repeat dose after at least 7 days (maximum: 750 mg/single dose; 1,500 mg per course). May repeat course of therapy if anemia reoccurs. Do not use more than 1000mg in one infusion.
≥50 kg: 750 mg on day 1; repeat dose after at least 7 days (maximum: 750 mg/single dose; 1,500 mg per course). May repeat course of therapy if anemia reoccurs.
Iron deficiency in heart failure with reduced ejection fraction (off-label use):
Note: Patients may or may not be anemic. Iron deficiency in clinical trials was defined as a serum ferritin level <100 mcg/L or a serum ferritin level of 100 to 300 mcg/L if transferrin saturation is <20% (Anker 2009; Ponikowski 2015).
IV: 200 mg once weekly (until iron repletion is achieved), and then 200 mg once every 4 weeks during maintenance (starting at week 8 or 12, depending on the required iron-repletion dose) (Anker 2009) or 500 or 1,000 mg/dose at baseline and week 6, followed by 500 mg/dose at weeks 12, 24, and 36 if iron deficiency is still present (dose based on screening weight and hemoglobin values; refer to protocol for specific details; Ponikowski 2015).
Restless legs syndrome (off-label use): IV: 500 mg on day 1; repeat after 5 days (AAN [Winkelman 2016]).
This patient was diagnosed as having iron deficiency anemia probably from acid peptic disease, with no increase in his ischemic heart disease. He could not take oral iron because of the GI side effects. He was given an infusion of FCM 1000 mg IV followed by another of 500 mg a week later, his dose of enalapril was adjusted and he was prescribed ranitidine orally for 6 weeks. Aspirin was stopped and he was advised to avoid NSAIDs. His symptoms began to improve within a week. Serum ferritin was 300 ng/dl after 3 months and Hb was 13gm/dl.