Heart failure is a progressive chronic syndrome characterized by decrease in functional status and quality of life, and an increased morbidity and mortality. Various developments with regards to early diagnosis and effective management have aimed to bring down the incidence of heart failure hospitalisations and mortality in heart failure patients. In India, the prevalence was estimated to be around 1.2/1000 people in the INDUS study. (1) Once developed, heart failure has a 1-year mortality rate of 7.2% and a 1-year hospitalization rate of 31.9% in patients with chronic heart failure, and in patients hospitalized for acute heart failure, these rates increase to 17.4% and 43.9%. (2) Worldwide, the burden of heart failure has increased to an estimated 23 million people.
The following article will focus on the ice-berg phenomenon in heart failure diagnosis in community and how far have we come with latest treatment options in addressing this huge burden on health care facilities across the world.
HF: The ice-berg phenomenon
As prevalence rates of heart failure are high and expected to rise in the near future because of improved survival from acute cardiac events and the aging of the general population, thus HF management has come to the front-stage of non-communicable disease management programmes. But prior to effective management is the unmet need for early and accurate diagnosis of this condition.
"Two monsters in disguise": the couplet of misdiagnosis and under diagnosis.
Although the prevalence of HF is highest in older people, diagnosis and management are likely to be least comprehensive in long-term care. In this setting, where access to health services may be limited, acute care often takes precedence over chronic care and preventative needs.
Unmet need for early and accurate diagnosis in HF
Early detection of heart failure by general practitioners (GPs) is hampered by the lack of specificity of symptoms, the presence of comorbidities, and limited access to echocardiography. Thorough physical examination in combination with echocardiography can improve the accuracy of CHF diagnostics. (3,4)
Riet et al have shown that in community-dwelling persons aged 65 years or more with shortness of breath on exertion, unrecognized heart failure is common with a prevalence of 15.7%. (5) Most patients who have undetected heart failure belong to the category of HF with preserved ejection fraction (discussed later).Their findings also suggest that GPs (and pulmonologists) seem to be less aware of heart failure in patients with COPD and that dyspnoea, abnormal pulmonary breathing sound, and fatigue could easily be misinterpreted as 'respiratory symptoms'. As long-term care residents are often unable to attend outside clinics or diagnostic facilities, the lack of availability of echocardiography in this setting further complicates diagnosis and management. (6)
Patients with heart failure present with a variety of symptoms, most of which are non- specific. Even the classical symptoms of dyspnea, edema and orthopnea havelimited sensitivities ranging from 21-66%. (7) While data on undiagnosed HF are inherently difficult to obtain, current evidence suggests that an accurate diagnosis may be missed in up to half of cases. (8)
In this regard, Hancock et al in HFinCH study arrived at the following conclusion: " Heart failure was diagnosed in almost a quarter of residents: the prevalence was substantially higher than in other populations. The majority of heart failure cases were undiagnosed, while three-quarters of previously recorded cases were misdiagnosed. Common symptoms and signs appear to have little clinical utility in this population. Early, accurate differential diagnosis is key to the effective management of heart failure; this may be failing in long-term care facilities" (8)
How to tackle the shortcomings of diagnosis?
When the initial symptomatology and clinical examination are limited by subpar sensitivities and specificities, then clinicians are more inclined to base their diagnosis on investigative findings.
In the initial evaluation of HF, guidelines suggest all patients with suspected heart failure should have an electrocardiogram. Abnormalities such as left ventricular hypertrophy, evidence of previous myocardial infarction or arrhythmias may be seen on the electrocardiogram, which is a widely available tool for GPs. An abnormal ECG has a relatively high sensitivity for a diagnosis of heart failure of 89% (95% CI 77–95%) but a moderate specificity of 56% (95% CI 46–66%) suggesting, that heart failure is quite unlikely in the presence of a normal ECG. In a primary care setting almost 60% of HF diagnosis can thus be made by ECG. Patients may benefit from further management of abnormal ECG findings such as atrial fibrillation, where anticoagulation to prevent thromboembolic events may be indicated. (9)
Next comes the role of natriuretic peptides (NPs) and echocardiography. Both B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) have high diagnostic power and are applicable to HFrEF and HFpEF. In situations when echocardiography is not immediately available, examination of NPs allows identification of patients requiring further cardiac evaluation by determining the likelihood of HF. In patients with NP values below the cut-off, HF can be excluded because the negative predictive value of NPs is very high (0.94 to 0.98). (10) There are increasing numbers of novel biomarkers such as soluble suppression of tumorigenicity-2 (ST2), galectin-3, and high-sensitivity cardiac troponin, which can be used for additive risk stratification in HF patients. (11)
Echocardiography is the most useful test providing immediate information, including systolic and diastolic function of LV and right ventricle (RV), chamber size, wall thickness, and valve abnormalities. Physicians can establish the precise diagnosis of HF and set up a treatment plan based on echocardiographic findings.
From drugs to devices, how far have the latest treatment modalities addressed the menace of HF?
Heart failure has traditionally been broadly sub-classified according to the left ventricular ejection fraction (LVEF) into 3 categories: heart failure with preserved ejection fraction (LVEF 50%), heart failure with midrange ejection fraction (LVEF 41%-49%), and heart failure with reduced ejection fraction (HFrEF, in which the LVEF is 40% or less). The risk factors, diagnostic algorithms and management strategies differ for these 3 varieties, but they share a common phenotype of dyspnea, congestive symptoms, fatigability etc. (1)
While on one hand we have various drugs that reduce HF hospitalization and mortality in HFrEF like betablockers, ACE-Inhibitors, ARBs, aldosterone antagonists and the latest additions to this armamentarium being ARNIs and SGLT2 inhibitors, on the other hand, there are only limited effective management strategies for the probably more common HFpEF. But a common denominator in drug therapy across all types of heart failures is the use of diuretics for relief of dyspnea, pedal edema, and other congestive symptoms. (12)
A unified approach to management: What's the latest from guidelines?
The 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment incorporates several emerging aspects in the treatment of heart failure and is summarised in figure 1. (12) Physicians should be well acquainted with all the available diagnostic tools for early diagnosis. The reason is that they are the first level of contact with patients, thus they can play the most vital role in overcoming the problem of misdiagnosis and underdiagnosis. They should be more vigilant in patients approaching them with respiratory symptoms like dyspnea or other non-specific complaints like fatigue. It is advisable that HF should always be ruled out in these patients.
The algorithm advocates use of state of the art diagnostic modalities in addition to classical signs and symptoms to diagnose heart failure. Both ACC and ESC guidelines promote the use of ARNIs/ACE-inhibitors/ARBs along with beta-blockers and optimum doses of diuretics as first line treatment and suggests additions in different scenarios there on like renal dysfunction, persistent volume overload, etc.
Edema and dyspnea: "A call for decongesting the traffic"
Expansion of extracellular fluid volume is central to the pathophysiology of heart failure. Increased extracellular fluid leads to elevated intracardiac filling pressures, resulting in a constellation of signs and symptoms of heart failure referred to as congestion. Loop diuretics are one of the cornerstones of treatments for heart failure.
These drugs reversibly, inhibit the Na+⁄2Cl-⁄K+ co-transporter of the thick ascending loop of Henle where one-third of filtered sodium is reabsorbed. This causes decreased sodium and chloride reabsorption and increased diuresis. Loop diuretics also enhance the synthesis of prostaglandins, which cause renal and venous dilatation. This explains some of the cardiac effects, such as reduction in pulmonary wedge pressure.
Loop diuretics include furosemide, bumetanide, torsemide and ethacrynic acid. While the bioavailability of oral furosemide ranges from 40 to 80%, the bioavailability of torsemide and bumetanide exceeds 80%; so these two molecules may be more effective in treating patients suffering from HF. (13)
Morbidity and mortality for all grades of symptomatic chronic heart failure are high, with a 20-30% one year mortality in mild to moderate heart failure and a greater than 50% one year mortality in severe heart failure. (7) A comprehensive use of clinical, biochemical and imaging modalities is required to diagnose the condition early so that effective management can be initiated in time to prevent the complication of recurrent admissions and mortality. The latest developments in drug and device therapy have brought us a long way to improve the quality of life for HF patients, but the age-old and much trusted diuretic therapy remains the cornerstone in managing congestive symptoms of all HF phenotypes.
1. Chaturvedi V, Parakh N, Seth S, Bhargava B, Ramakrishnan S, Roy A, et al. Heart failure in India: The INDUS (INDia Ukieri Study) study. J Pract Cardiovasc Sci 2016;2:28-35
2. Murphy SP, Ibrahim NE, Januzzi JL Jr. Heart Failure With Reduced Ejection Fraction: A Review. JAMA. 2020 Aug 4;324(5):488-504. doi: 10.1001/jama.2020.10262. Erratum in: JAMA. 2020 Nov 24;324(20):2107.
3. Barents M, van der Horst IC, Voors AA, Hillege JL, Muskiet FA, de Jongste MJ. Prevalence and misdiagnosis of chronic heart failure in nursing home residents: the role of B-Type natriuretic peptides. Neth Heart J 2008;16:123–128. 10.
4. Remes J, Miettinen H, Reunanen A, Pyorala K. Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J 1991;12:315–321.
5. van Riet EE, Hoes AW, Limburg A, Landman MA, van der Hoeven H, Rutten FH. Prevalence of unrecognized heart failure in older persons with shortness of breath on exertion. Eur J Heart Fail. 2014 Jul;16(7):772-7. doi: 10.1002/ejhf.110.
6. Barriers to accurate diagnosis and effective management of heart failure in primary care: qualitative study. Fuat A, Hungin AP, Murphy JJ BMJ. 2003 Jan 25; 326(7382):196.
7. Watson RD, Gibbs CR, Lip GY. ABC of heart failure. Clinical features and complications. BMJ. 2000;320(7229):236-239. doi:10.1136/bmj.320.7229.236
8. Hancock HC, Close H, Mason JM, et al. High prevalence of undetected heart failure in long-term care residents: findings from the Heart Failure in Care Homes (HFinCH) study. Eur J Heart Fail. 2013;15(2):158-165.
9. Dickstein K, Cohen-Solal A, Filippatos G, et al., ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM), Eur J Heart Fail, 2008;10(10):933–89.
10. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–2200.
11. Savic-Radojevic A, Pljesa-Ercegovac M, Matic M, Simic D, Radovanovic S, Simic T. Novel Biomarkers of Heart Failure. Adv Clin Chem. 2017;79:93-152. doi: 10.1016/bs.acc.2016.09.002.
12. Writing Committee, Maddox TM, Januzzi JL Jr, Allen LA, Breathett K, Butler J, et al. 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Feb 16;77(6):772-810.
13. Casu G, Merella P. Diuretic Therapy in Heart Failure - Current Approaches. Eur Cardiol. 2015;10(1):42-47. doi:10.15420/ecr.2015.10.01.42