How To Lose Weight With Hypertrophic Cardiomyopathy

B Barts Health NHS Trust, London, UK, William Harvey Research Institute, Queen Mary University London, UK and Institute for Cardiovascular Science, University College London, London, UK

Hypertrophic cardiomyopathy is one of the most frequently diagnosed primary conditions of the heart muscle. It is considered to be inherited, caused by genetic mutations encoding for sarcomere proteins. The marked heterogeneity in clinical manifestations and natural course of the disease, even among family members sharing the same genetic mutation, has raised the question of non-genetic environmental factors contributing to the phenotype. Obesity has been associated with worse cardiovascular outcomes in the general population. Its prevalence is increased in hypertrophic cardiomyopathy, and the two conditions share some similar pathophysiological and clinical characteristics. In this review, we aim to summarise the effects of obesity in the cardiac phenotype, the symptoms and management in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a primary condition of the heart muscle characterised by increased left ventricular (LV) wall thickness that cannot be explained by other cardiac, systemic or metabolic conditions. HCM is one of the most common cardiomyopathies, with a prevalence of 1:500, although newer evidence suggests that it is much more common.1 The variable penetrance, even in common genetic ground, suggests that the cause is related to multiple different factors, including non-heritable somatic mutations or non-genetic environmental factors. The notion of cardiovascular risk factors acting as disease modifiers in HCM has previously been entertained, with data supporting hypertension and obesity as a triggering factor for HCM phenotype in carriers.2, 3 Obesity is a global epidemic with well-known effects on cardiovascular disease and can lead to cardiac changes similar to those seen in HCM.4 In this review, we summarise the effects of obesity on the cardiac phenotype, the symptoms and their management in patients with HCM.

Hypertrophic Cardiomyopathy (hcm): Causes And Treatments

HCM is considered a genetic condition, inherited in an autosomal dominant pattern. A genetic mutation can be identified in ∼40% of HCM cases.5 The mutations affect the proteins of the sarcomere, with

Mutations seen in ∼70% of gene-positive probands.6 The mutant proteins trigger a cascade of events at the cellular level, eventually leading to metabolic and architectural changes.7

The metabolic milieu in HCM is complex and remains the object of ongoing research. It is suggested that inadequate sarcomere function, mitochondrial dysfunction and a shift from fatty acid oxidation to an increase in glucose oxidation result in inefficient energy utilisation and energy depletion.8

Hypertrophic Cardiomyopathy, Hcm And Hocm

HCM is characterised by myocyte hypertrophy and disarray, interstitial fibrosis and medial hypertrophy of small vessels. Macroscopically, hypertrophy is usually asymmetric and involves the basal intraventricular septum wall, although different patterns, such as apical or concentric hypertrophy, have also been described. The hypertrophy, in combination with other structural changes seen in HCM (elongated mitral valve leaflets and papillary muscles abnormalities), contribute to obstruction of blood flow during systole and increased pressure gradient across the LV outflow track (LVOT), most commonly or occasionally the mid cavity. The haemodynamic changes at the narrowed outflow track during systole drag the mitral valve leaflet toward the septum, aggravating obstruction and preventing coaptation of the mitral valve leaflets. Exacerbation of obstruction on exertion can lead to reduced cardiac output because of reduced blood flow crossing the LVOT toward the aorta and loss of blood volume from the mitral regurgitant jet. Almost two-thirds of patients with HCM will have LVOT obstruction at rest, with provocation manoeuvres (Valsalva) or on stress echocardiography.6, 9, 10

The ventricular function is usually hyperdynamic, as an initial response to the sarcomere changes. Diastolic dysfunction with preserved ejection fraction is usually seen with progression. Heart failure (HF) with systolic impairment will affect a smaller number of patients.11

HCM is the primary cardiac cause of sudden death in young people.12 Atrial fibrillation (AF) and malignant ventricular arrhythmias are the main components of the arrhythmic profile.6, 11

Hcm In Young Adults And Student Athletes

Coronary microvascular dysfunction (CMD) and reduced coronary vasodilator reserve have been demonstrated in hypertrophied hearts, contributing to the burden of symptoms and arrhythmic risk. Morphological changes of the small vessels (medial hypertrophy, intima hyperplasia and smaller luminal size) and haemodynamic changes (extravascular compression because of ventricular hypertrophy, diastolic dysfunction and LVOT obstruction) compile the pathophysiological substate.13, 14 Interestingly, mutation carriers can have evidence of microvascular dysfunction, without a clinical phenotype, posing the hypothesis that CMD may be one of the early signs of HCM.14, 15

The clinical spectrum and natural course of the condition is heterogeneous and ranges from complete absence of symptoms to HF symptoms or sudden death. The most common symptom is breathlessness on exertion because of the underlying obstruction. Chest pain is less often seen and accompanies breathlessness. Presyncope and syncope are also elements of the clinical phenotype and could be related to obstruction, arrhythmias or autonomic dysfunction. Patients can remain relatively asymptomatic, progress to end-stage HF (5–10%), or experience sudden death.16 Results from the Sarcomeric Human Cardiomyopathy (SHaRe) registry highlighted the importance of young age at diagnosis and genetic mutations as predictors of adverse outcome.17 There is ongoing research in clinical outcome determinants and disease modifiers.

Obesity, defined as excessive fat accumulation, is a well-established risk factor for adverse cardiovascular outcomes. The body mass index (BMI), which is the ratio of body weight to height, is commonly used to quantify obesity. High BMI is associated with an increased risk of cardiovascular disease and mortality. In 2015, an estimated 4 million deaths were related to high BMI, with 70% considered to be from cardiovascular causes.18 The pathophysiological interplay between obesity and cardiovascular disease involves multiple factors, including increased cardiac stress, altered haemodynamics, sympathetic activation and an increased prevalence of cardiovascular risk factors, such as diabetes, hypertension, hyperlipidaemia and sleep apnoea.

Hypertrophic Cardiomyopathy Treatment (hcm)

Obesity is associated with increased prevalence of coronary artery disease, HF, AF and sudden cardiac death.19 Young patients with obesity who experience sudden death have been found to have a high prevalence of unexplained LV hypertrophy and coronary artery disease compared with patients without non-obesity.20 Increased oxygen demands and increased blood volume in obesity result in a haemodynamic milieu that triggers LV dilatation and LV mass augmentation. In addition, neurohormonal activation in obesity with insulin and leptin-induced effects promotes cardiac remodelling.19

HF and high BMI appear to be linked in a dose-dependent way. A meta-analysis in 2016 found a 41% increase in HF risk for every 5 kg/m

Increase in BMI.21 High BMI and long-standing severe obesity are strong risk factors for the development of heart failure. Obesity is a considerable contributor to HF with preserved ejection fraction. Elevated leptin levels, renal/aldosterone activation and low brain natriuretic peptide (BNP) levels are probable causes of increased blood volume and inflammation on a background of sympathetic activation, mechanical stress and increased prevalence of cardiovascular factors. In the long term, these pathophysiological changes lead to altered cardiac geometry with LV hypertrophy (with or without right ventricular hypertrophy) and diastolic dysfunction.22

What Is The Difference Between Dilated Cardiomyopathy And Hcm?

Obesity accelerates the atherosclerotic process in the coronary arteries. Microvascular circulation, a key regulator of coronary flow reserve, is also affected via changes in mechanical forces, endothelial function, and inflammatory and neurohumoral activation.23–25 In a study by Bajaj

AF is more frequently encountered in overweight and obese individuals. In the Framingham study, the risk of AF was increased by 4% with every 1 unit increase in BMI.27 Many studies support a strong link between high BMI and onset and progression of AF. The pathophysiological substrate is complex and not fully clarified. Obesity triggers the electroanatomical remodelling of the left atrium, favouring the onset of AF. High output state, increased filling pressures and diastolic dysfunction, low-grade inflammation, autonomic activation and coexistence of other AF-related factors (hypertension, obstructive sleep apnoea and chronic kidney disease) probably contribute to AF remodelling.28, 29

Another interesting change in individuals with obesity is the metabolic switch toward fatty acid oxidation with decrease in glucose oxidation. This change in myocardial metabolism triggers a cascade that results in a less energy-efficient state.30 In combination with lipotoxicity originating from intracellular accumulation, the metabolic alterations in obesity could predispose to contractile dysfunction.31, 32

Unraveling The Genotype‐phenotype Relationship In Hypertrophic Cardiomyopathy: Obesity‐related Cardiac Defects As A Major Disease Modifier

Interestingly, the distribution of body adipose tissue, specifically visceral adipose tissue, appears to alter the cardiometabolic profile and increase cardiovascular risk.29, 33 The Multi-Ethnic Study of Atherosclerosis (MESA) study highlighted the association between pericardial adipose tissue and worse cardiovascular outcomes.34 According to research data, obesity is associated with epicardial fat accumulation and increased inflammatory activity.35, 36 Epicardial fat can channel systemic inflammatory effects to adjacent tissues, leading to coronary artery disease, microvascular dysfunction, AF and HF.37–39

The clinical phenotype of obesity exhibits similarities with that of HCM. Furthermore, the prevalence of obesity appears to be greater among individuals with HCM, prompting inquiry as to whether obesity increases susceptibility to HCM or exacerbates its clinical manifestation40 (Fig 1). Elevated BMI among patients with asymptomatic HCM could be attributable to exercise restrictions imposed upon them, whether voluntarily in response to their diagnosis or at the instruction of their physician. Additionally, weight gain might result from diminished activity because of symptomatic limitations.41

Hypertrophic cardiomyopathy and obesity interplay. Similar pathophysiological and clinical manifestations are observed in both HCM and obesity cardiomyopathy. Metabolic activity, microvascular dysfunction, adrenergic drive, and hypertension in obesity could potentially trigger/exacerbate the HCM clinical phenotype. AF

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