Left Ventricular Diastolic Function
Left ventricular (LV) diastolic function refers to the heart’s ability to relax and fill with blood during the diastolic phase of the cardiac cycle. This crucial process ensures adequate blood supply to the body and is a fundamental aspect of overall cardiovascular health. Impairment of this function, known as diastolic dysfunction, can lead to serious health conditions, including various forms of heart failure.
Background
Section titled “Background”Measuring left ventricular diastolic function involves assessing several parameters, typically through non-invasive imaging techniques such as echocardiography and cardiac magnetic resonance (CMR) imaging.[1]Key measurements include radial and longitudinal peak early diastolic strain rate (PDSRrr and PDSRll), and maximum body surface area-indexed left atrial volume (LAVmaxi).[1] Other important echocardiographic measures include the peak velocity of the transmitral E-wave (Mv-E) and A-wave (Mv-A), their ratio (E/A), deceleration time of Mv-E (DecTime), isovolumetric relaxation time (IVRT), and the peak velocity of the lateral mitral annulus in early diastole (E′) and its ratio to Mv-E (E/E′).[2]These measurements provide insights into how effectively the left ventricle relaxes and fills, reflecting the health and mechanics of the heart muscle.
Biological Basis
Section titled “Biological Basis”Left ventricular diastolic function is a complex physiological trait influenced by a combination of genetic and environmental factors.[1] Large-scale genome-wide association studies (GWAS) have been instrumental in identifying genetic variants associated with cardiac structure and function, including diastolic function.[1], [2] These studies utilize common and rare variant association analyses to uncover the genetic architecture underlying these traits.[1] For instance, specific diastolic function traits like PDSRll, PDSRrr, and LAVmaxi show SNP-based heritability, explaining a notable proportion of variance (e.g., 12% for PDSRll, 13% for PDSRrr, and 21% for LAVmaxi).[1] Researchers have identified multiple independent genetic loci linked to diastolic function, with lead variants often assigned to likely causal genes through detailed variant annotations and functional genomic data.[1] While identified genetic variants typically have small individual effect sizes, their collective impact contributes to the overall function.[2] Further research also considers the role of Loss-of-Function (LoF) mutations in influencing these cardiac phenotypes.[1]
Clinical Relevance
Section titled “Clinical Relevance”Accurate of left ventricular diastolic function is clinically vital for diagnosing and classifying left ventricular diastolic dysfunction, particularly in conditions like heart failure with preserved ejection fraction (HFpEF) and asymptomatic left ventricular diastolic dysfunction with preserved ejection fraction (DDpEF).[2]Diastolic dysfunction is a precursor to heart failure and is associated with various cardiovascular risk factors.[1] Early identification of impaired diastolic function allows for timely interventions and management strategies, which can significantly impact patient outcomes and prognosis.[1]The intricate relationship between left atrial function and right ventricular function also underscores the systemic interdependence of cardiac chambers in maintaining overall heart health.[1]
Social Importance
Section titled “Social Importance”The prevalence of heart failure, including HFpEF, represents a substantial public health challenge globally. By enhancing our understanding of the genetic and environmental determinants of left ventricular diastolic function, researchers aim to develop more effective preventative measures, improve diagnostic tools, and refine treatment approaches. Large-scale population studies, such as those leveraging data from the UK Biobank, contribute to a broader epidemiological understanding of cardiovascular health, ultimately benefiting public health initiatives and patient care.[1]Early and precise assessment of diastolic function is key to mitigating the burden of heart disease on individuals and healthcare systems.
Methodological and Generalizability Considerations
Section titled “Methodological and Generalizability Considerations”The robust identification of genetic and environmental determinants of left ventricular diastolic function is subject to several methodological and generalizability limitations. A primary concern is the predominant focus on participants of European ancestry in large-scale genetic analyses, such as the 34,242 individuals of European ancestry used for genetic analysis in one study, with a validation set of 10,924.[1]While this provides substantial statistical power within this group, it significantly limits the direct generalizability of the findings to populations of other ancestries, where genetic architectures, environmental exposures, and disease prevalence may differ substantially. Future research must broaden ancestral representation to ensure equitable clinical translation of these genetic insights across diverse global populations.
Furthermore, despite the large sample sizes employed, the genetic variants identified often exhibit small individual effect sizes, collectively explaining only a modest percentage of the variance in left ventricular diastolic function phenotypes.[2] This inherent characteristic of complex traits suggests that current studies may still have modest statistical power to detect all subtle genetic associations, particularly those with very small effects or within specific genetic contexts.[2] Additionally, certain causality assessments did not include explicit multiplicity adjustments for all sensitivity analyses, which could potentially lead to an overestimation of the confidence in reported causal relationships.[1] Addressing these statistical nuances is critical for robustly identifying and validating genetic determinants.
Phenotypic Complexity and Challenges
Section titled “Phenotypic Complexity and Challenges”Left ventricular diastolic function is a highly complex physiological trait, and its precise and interpretation present significant challenges. Cardiac imaging parameters, such as transmitral A-wave velocity, are known to be highly susceptible to variations in ventricular loading conditions, making their isolated interpretation difficult without considering the broader context of left ventricular filling patterns.[2] This inherent variability can introduce noise into phenotypic data, potentially obscuring true genetic signals.
The heterogeneity in both phenotypic assessment methodologies and study designs across different research cohorts can further impede the consistent detection and replication of genetic associations.[2] While advanced techniques like cardiac magnetic resonance imaging (CMR) with machine learning segmentation offer high-resolution measurements of parameters such as radial and longitudinal peak early diastolic strain rate and maximum left atrial volume.[1] the dynamic nature of cardiac function means that these measurements are snapshots influenced by numerous physiological factors at the time of assessment. A deeper understanding of how these diverse techniques capture the underlying biology of diastolic function is crucial for advancing the field.
Environmental Influences and Unexplained Variation
Section titled “Environmental Influences and Unexplained Variation”The understanding of left ventricular diastolic function is further complicated by the pervasive influence of environmental factors and their intricate interactions with genetic predispositions. Although studies account for demographic and clinical confounders such as age, sex, body surface area, systolic blood pressure, and the presence of diabetes.[1]a vast array of other environmental and lifestyle factors remain uncharacterized or are difficult to quantify comprehensively. These include dietary patterns, physical activity levels, chronic stress, and exposure to environmental pollutants, all of which are known to modulate cardiovascular health.
The interplay between these unmeasured environmental factors and an individual’s genetic makeup contributes significantly to the “missing heritability” phenomenon, where identified genetic variants explain only a small proportion of the total phenotypic variance.[2]This indicates that a substantial portion of the variability in left ventricular diastolic function is either influenced by numerous yet-to-be-discovered genetic variants, complex gene-environment interactions, or rare genetic variants not captured by common variant association studies. Further research exploring these multifaceted interactions is essential to fully elucidate the etiology of diastolic dysfunction.
Variants
Section titled “Variants”Genetic variations play a crucial role in influencing left ventricular diastolic function, a key indicator of heart health. Several genes and their associated single nucleotide polymorphisms (SNPs) have been identified as contributors to the complex genetic architecture underlying diastolic function. These variants can impact myocardial elasticity, cellular signaling, and protein homeostasis, ultimately affecting the heart’s ability to relax and fill with blood efficiently.
Variants in genes like TTN (Titin) and BAG3 (BCL2-associated athanogene 3) are particularly relevant due to their fundamental roles in cardiomyocyte structure and function. TTN encodes for titin, a giant protein essential for myocardial elasticity and passive stiffness, and its variants, such as rs2562845 , rs2042995 , and rs111692972 , can alter myocardial compliance, directly impacting diastolic relaxation. Truncating variants in TTNare a well-established cause of dilated cardiomyopathy, a condition characterized by impaired diastolic function.[3] Similarly, BAG3 is involved in protein quality control and cellular stress responses within cardiomyocytes, and variants like rs72840788 and rs2234962 can disrupt these processes, leading to protein accumulation and cellular dysfunction that impairs the heart’s ability to relax. While TTN and BAG3are known cardiomyopathy-linked genes, they were not identified as candidates for transcriptome-wide association studies in some analyses due to specific expression quantitative trait locus (eQTL) thresholds.[3] The TTN-AS1 variant rs6755784 , located in an antisense RNA gene to TTN, may indirectly modulate TTN expression, further influencing myocardial characteristics and diastolic performance.
Other genetic loci impact diastolic function through diverse molecular pathways. The ATXN2 (Ataxin 2) gene, involved in RNA processing, and its variant rs653178 , have been linked to left ventricular diastolic dimensions.[2] Alterations in ATXN2 expression or function can influence cardiac remodeling and cellular stress responses, contributing to changes in heart structure that affect diastolic filling. Adjacent to ATXN2, the rs7310615 variant in SH2B3 (SH2B adaptor protein 3) is associated with SH2B3expression, a gene involved in cytokine signaling and immune regulation.[2] Dysregulation of inflammatory pathways mediated by SH2B3could contribute to myocardial fibrosis or stiffness, impairing diastolic function.
Further variants implicated in left ventricular diastolic function includers55756123 in the ZEB2P1 - LDB2 region, rs10117876 near TUBB4BP6 - BRINP1, and rs2801617 in the LINC02335 - HNF4GP1 locus. These regions contain genes or regulatory elements that may influence cardiac cell growth, differentiation, or metabolism, with downstream effects on myocardial properties. For instance, MYO1C (Myosin IC) variants, such as rs7502466 and rs2302455 , may affect the mechanics of non-muscle myosin, which contributes to cellular contractility, adhesion, and membrane dynamics, thereby indirectly influencing the overall stiffness and relaxation properties of the heart muscle. Understanding the specific mechanisms by which these variants influence gene activity and cellular pathways is crucial for unraveling the intricate genetic underpinnings of diastolic heart health.[1]
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs2562845 rs2042995 | TTN-AS1, TTN | heart failure left ventricular ejection fraction left ventricular diastolic function left ventricular systolic function left ventricular mass |
| rs111692972 | TTN | left ventricular diastolic function left ventricular structural |
| rs7310615 | SH2B3 | circulating fibrinogen levels systolic blood pressure, alcohol consumption quality systolic blood pressure, alcohol drinking mean arterial pressure, alcohol drinking mean arterial pressure, alcohol consumption quality |
| rs72840788 rs2234962 | BAG3 | electrocardiography hypertrophic cardiomyopathy heart function attribute left ventricular diastolic function left ventricular systolic function |
| rs6755784 | TTN-AS1 | left ventricular systolic function heart function attribute left ventricular mass left ventricular diastolic function left ventricular ejection fraction |
| rs653178 | ATXN2 | myocardial infarction inflammatory bowel disease eosinophil percentage of leukocytes eosinophil count eosinophil percentage of granulocytes |
| rs55756123 | ZEB2P1 - LDB2 | left ventricular diastolic function |
| rs10117876 | TUBB4BP6 - BRINP1 | left ventricular diastolic function |
| rs2801617 | LINC02335 - HNF4GP1 | left ventricular mass left ventricular diastolic function left ventricular systolic function |
| rs7502466 rs2302455 | MYO1C | left ventricular diastolic function left ventricular systolic function left ventricular function |
Defining Left Ventricular Diastolic Function
Section titled “Defining Left Ventricular Diastolic Function”Left ventricular diastolic function refers to the heart’s ability to relax and fill with blood during diastole, the resting phase between heartbeats.[4]This physiological process is fundamental for ensuring adequate cardiac output and maintaining overall circulatory health. Impaired left ventricular diastolic function, often termed diastolic dysfunction, signifies that the left ventricle is unable to properly relax or fill, which can lead to elevated filling pressures and, subsequently, to various forms of heart failure.[5] Conceptually, it is a complex mechanism influenced by multiple factors including myocardial relaxation properties, the stiffness of the cardiac chambers, and the intricate functional interplay between the ventricle and the atrium.[4]
Approaches and Operational Definitions
Section titled “Approaches and Operational Definitions”The assessment of left ventricular diastolic function employs various imaging modalities, each with specific operational definitions for key parameters. Traditionally, echocardiography has been a primary method, utilizing Doppler techniques to evaluate the patterns of ventricular filling.[6] More recently, Cardiac Magnetic Resonance (CMR) imaging, enhanced by machine learning segmentation and motion tracking algorithms, has enabled precise quantification of diastolic function parameters.[1] CMR feature tracking, for instance, can assess global longitudinal strain, and its measurements have been correlated with invasive indices of diastolic function.[7] Operational definitions for commonly measured parameters include the radial and longitudinal peak early diastolic strain rates (PDSRrr and PDSRll, respectively), which are quantitative indicators of myocardial relaxation velocities.[1]Another crucial metric is the maximum body surface area-indexed left atrial volume (LAVmaxi), which serves as an important surrogate marker for chronically elevated left ventricular filling pressures.[1]Other routinely assessed cardiac characteristics, such as left ventricular mass (LVM), left atrial maximum and minimum volumes, left atrial stroke volume, and left atrial emptying fraction, are typically indexed to body surface area (BSA).[1]This indexing to BSA is a standardized practice that accounts for individual differences in body size, thereby ensuring more comparable and clinically relevant measurements.[8]
Classification of Diastolic Dysfunction and Clinical Significance
Section titled “Classification of Diastolic Dysfunction and Clinical Significance”Diastolic dysfunction is often classified into different grades, typically derived from echocardiographic findings, to reflect the varying degrees of impairment in left ventricular relaxation and filling pressures.[4] While specific grading systems are not detailed, it is recognized that advanced imaging techniques, such as speckle-tracking echocardiography, have the potential to further refine diagnosis and classification.[2]Diastolic dysfunction with preserved ejection fraction (DDpEF) describes the presence of echocardiographic evidence of diastolic dysfunction in asymptomatic individuals who do not yet manifest overt heart failure .
Evolution of Scientific Understanding and Diagnostic Modalities
Section titled “Evolution of Scientific Understanding and Diagnostic Modalities”The understanding and of left ventricular diastolic function have evolved significantly from early descriptions to sophisticated modern techniques. Initially, the assessment of cardiac function primarily focused on systolic parameters, but the recognition of heart failure with preserved ejection fraction (HFpEF) highlighted the critical role of diastolic function.[9] Key advancements in non-invasive imaging, particularly Doppler echocardiography, revolutionized the field by enabling detailed visualization of left ventricular filling patterns and the quantification of parameters like transmitral inflow velocities and mitral annular excursion.[6] The standardization of echocardiographic measurements, including left ventricular anatomic dimensions, further refined diagnostic consistency and allowed for the appreciation of the broader scope of cardiac dysfunction in the community.[10]Further evolution saw the integration of advanced echocardiographic techniques, such as speckle-tracking echocardiography for global longitudinal and circumferential strain, and the emergence of cardiovascular magnetic resonance (CMR) imaging as a powerful tool.[11]CMR, particularly with machine learning segmentation and motion tracking, now allows for the precise of parameters like radial and longitudinal peak early diastolic strain rate (PDSRrr and PDSRll) and maximum body surface area-indexed left atrial volume (LAVmaxi), which are crucial for a comprehensive assessment of diastolic function.[1] These technological advancements have deepened the understanding of the underlying pathophysiology, including insights into cardiomyocyte stiffness and the role of factors like advanced glycation end-products in age-related diastolic dysfunction.[12]
Global Burden and Demographic Patterns
Section titled “Global Burden and Demographic Patterns”Left ventricular diastolic dysfunction represents a significant global health burden, contributing substantially to the prevalence of heart failure, particularly HFpEF.[13]Large-scale epidemiological studies, such as the National Echo Database Australia (NEDA) involving over 436,000 individuals, have demonstrated the widespread presence of diastolic dysfunction and its association with mortality across diverse populations.[14]The prevalence and characteristics of diastolic dysfunction are strongly influenced by demographic factors, with age being a primary determinant; the aging heart naturally exhibits changes that predispose to diastolic dysfunction.[15] Sex also plays a crucial role, with studies consistently showing age- and sex-related influences on left ventricular mechanics and diastolic strain analysis.[16] Furthermore, ancestry and socioeconomic factors contribute to the observed patterns, as evidenced by research on heritability and genetic linkage of diastolic function in specific populations like hypertensive African Americans.[17]Comprehensive analyses, like those conducted on UK Biobank data, reveal that age, sex, body surface area, systolic blood pressure, pulse rate, and diabetes are significant predictors of diastolic function parameters such as peak diastolic strain rates and left atrial volume, underscoring the multifactorial nature of its epidemiological distribution.[1]
Epidemiological Trends and Determinants
Section titled “Epidemiological Trends and Determinants”Epidemiological trends indicate a rising appreciation of left ventricular diastolic dysfunction as a precursor to heart failure, highlighting its progression and impact on cardiovascular outcomes over time.[18]This increasing recognition is partly due to improved diagnostic capabilities and the growing prevalence of risk factors such as hypertension, diabetes, and obesity, which are strongly associated with impaired diastolic function.[19] The shift in focus to contemporary assessment of diastolic function, particularly in older adults, reflects a secular trend towards earlier identification and intervention for subclinical cardiac dysfunction.[20] Future projections and ongoing research are increasingly focusing on the genetic and environmental determinants of diastolic function to better understand these trends. Large-scale genome-wide association studies (GWAS) are identifying genetic variants associated with cardiac structure and function, including specific measures of diastolic filling and left atrial volume.[2]These genetic insights, combined with environmental factors and circulating biomarkers like C-reactive protein, are crucial for elucidating the complex interplay driving the changing patterns of diastolic dysfunction prevalence and its impact on cardiovascular health.[1]
Biological Background of Left Ventricular Diastolic Function
Section titled “Biological Background of Left Ventricular Diastolic Function”Left ventricular (LV) diastolic function refers to the heart’s ability to relax and fill with blood during diastole, the resting phase of the cardiac cycle. Far from being a passive process, diastole is a dynamic and complex sequence of physiological events involving active myocardial relaxation, intrinsic myocardial stiffness, and elastic recoil of the ventricular walls.[1] These intricate processes are continuously modulated by external factors such as ventricular loading conditions, heart rate, and the preceding systolic contractile function.[1]Optimal diastolic function is crucial for maintaining adequate LV filling and ensuring sufficient stroke volume, which are fundamental for overall cardiovascular health.
The Physiology of Cardiac Diastole
Section titled “The Physiology of Cardiac Diastole”The heart’s ability to efficiently fill with blood during diastole is a multi-faceted process that relies on the coordinated actions of myocardial relaxation, stiffness, and recoil. Myocardial relaxation, an active energy-dependent process, allows the heart muscle to lengthen and the ventricular chamber to expand, creating a pressure gradient that facilitates blood inflow from the left atrium.[1] Concurrently, the intrinsic stiffness of the myocardium and the elastic recoil of the ventricular walls influence how readily the ventricle can distend and accommodate the incoming blood volume.[1]Disruptions in these mechanisms can impair LV filling, leading to diastolic dysfunction, a condition that is a significant predictor of major adverse cardiovascular events and all-cause mortality.[1]Age is a prominent factor influencing diastolic function, with a natural decline observed as a hallmark of cardiac aging, often attributed to progressive pro-fibrotic changes and energetic pathway alterations within the myocardium.[1]Furthermore, systemic conditions significantly impact diastolic performance; for instance, diastolic blood pressure is causally associated with parameters like radial peak early diastolic strain rate (PDSRrr) and longitudinal peak early diastolic strain rate (PDSRll), while systolic blood pressure is linked to PDSRll.[1] Elevated total peripheral resistance also correlates with impaired diastolic function, indicating the critical role of ventriculo-vascular coupling in maintaining cardiac health.[1]The left atrial maximum volume (LAVmaxi), a measure of left atrial size, is functionally interdependent with right ventricular function, highlighting the interconnectedness of cardiac chambers in overall heart performance.[1]
Cellular and Molecular Mechanisms in Diastolic Function
Section titled “Cellular and Molecular Mechanisms in Diastolic Function”At the cellular level, the precise regulation of cardiomyocyte function and the extracellular matrix (ECM) are paramount for maintaining healthy diastolic function. Myocardial stiffness, a key determinant of diastolic properties, originates from the cardiomyocyte sarcomere, the fundamental contractile unit, as well as from the expansion and remodeling of extracellular matrix proteins.[1] For example, the actin-organizing formin protein Fhod3 has been identified as essential for the postnatal development and functional maintenance of the adult heart in animal models.[21] Alterations in these structural and regulatory proteins can directly impact the heart’s ability to relax and stretch, contributing to diastolic dysfunction.
Beyond structural components, several key biomolecules and signaling pathways play a regulatory role. C-type natriuretic peptide(CNP) is a crucial hormone involved in coordinating cardiac structure and function, with implications in blood pressure control and cardioprotective effects.[22]Furthermore, advanced glycation end-products (AGEs) have been linked to diastolic dysfunction in aging, even independently of myocardial structural changes, suggesting molecular mechanisms involving protein modifications.[23] Other biomolecules like sex hormone-binding globulin and the insulin-like growth factor-1 system, including its binding protein-7, have been investigated as potential biomarkers or contributors to heart failure with preserved ejection fraction, a condition often characterized by diastolic dysfunction.[24]
Genetic Architecture of Diastolic Traits
Section titled “Genetic Architecture of Diastolic Traits”The genetic contribution to left ventricular diastolic function is substantial, with studies revealing a polygenic architecture underlying these complex traits. Heritability estimates derived from SNP-based analyses indicate that common genetic variants explain a notable proportion of the variance in diastolic function measures, such as 12% for PDSRll, 13% for PDSRrr, and 21% for LAVmaxi.[1] These traits also exhibit varying degrees of genetic correlation, with a strong correlation observed between PDSRll and PDSRrr (0.85), suggesting shared genetic determinants for these specific myocardial deformation parameters.[1]Genome-wide association studies (GWAS) have identified multiple independent genetic loci associated with diastolic function, mapping to genes implicated in crucial biological processes like actin assembly, cardiomyocyte survival, and broader heart failure phenotypes.[1] For instance, specific lead variants are systematically evaluated for their functional consequences, utilizing tools like the Variant Effect Predictor (VEP) and Loss-of-Function Transcript Effect Estimator (LOFTEE), alongside expression quantitative trait loci (eQTL) data to link variants to gene expression and function.[1] Additionally, analyses of loss-of-function (LoF) mutations in protein-coding genes contribute to understanding the impact of rare genetic variants on diastolic phenotypes.[1]These genetic insights provide critical avenues for exploring the molecular mechanisms and developing targeted therapies for cardiovascular diseases characterized by diastolic dysfunction.
Systemic Influences and Pathophysiological Consequences
Section titled “Systemic Influences and Pathophysiological Consequences”Diastolic function is profoundly influenced by a range of systemic physiological and pathophysiological processes that extend beyond the heart itself. Metabolic disorders, such as type 1 and type 2 diabetes mellitus, are strongly associated with diastolic dysfunction, with glycemic control affecting LV diastolic function and a clear link to insulin resistance and metabolic syndrome.[25] Blood lipids also exert effects on the left ventricle, further highlighting the systemic metabolic context of cardiac health.[26] While C-reactive protein (CRP), a circulating biomarker of inflammation, shows a relationship with serum triglycerides, it has not been independently associated with diastolic function, suggesting complex inflammatory pathways may be involved.[1]The mechanical loading of the heart by the vascular system also plays a critical role. Elevated diastolic and systolic blood pressure, as well as increased total peripheral resistance, are causally linked to impaired diastolic function, emphasizing the concept of ventriculo-vascular coupling in disease progression.[1]These systemic disruptions can lead to cardiac remodeling, including myocardial interstitial fibrosis, which stiffens the ventricle and contributes to diastolic dysfunction.[27]Ultimately, a decline in diastolic function, often indicated by a stiffer ventricle (e.g., lower PDSRrr), has a causal relationship with the development of heart failure, underscoring its importance as a prognostic indicator and a target for therapeutic intervention.[1]
Cellular and Structural Remodeling Pathways
Section titled “Cellular and Structural Remodeling Pathways”Left ventricular diastolic function is critically dependent on a complex sequence of physiological processes involving myocardial relaxation, stiffness, and recoil -products (AGEs) is particularly implicated in the diastolic dysfunction observed in aging hearts, suggesting that non-enzymatic protein modifications contribute to altered myocardial properties . These measurements, including radial and longitudinal peak early diastolic strain rates (PDSRrr and PDSRll) and indexed left atrial maximum volume (LAVmaxi), help clinicians diagnose early stages of diastolic dysfunction, often before symptoms manifest.[1]Identifying individuals at high risk allows for personalized medicine approaches, enabling early interventions and prevention strategies to mitigate disease progression.
The utility of these assessments extends to understanding the influence of demographic and physiological factors. Research indicates that diastolic strain rates decline with age and are lower in men, suggesting age- and sex-specific reference values are important for accurate interpretation.[1]Multivariable analyses further demonstrate significant associations between diastolic function traits and factors like body surface area, pulse rate, and systolic blood pressure.[1] Recognizing these influences helps in refining risk stratification, ensuring that diagnostic criteria and risk models are appropriately adjusted for individual patient characteristics, thereby improving the precision of risk assessment and guiding tailored management plans.
Prognostic Indicator and Disease Progression
Section titled “Prognostic Indicator and Disease Progression”Left ventricular diastolic function serves as a powerful prognostic indicator, offering insights into the likely course of various cardiovascular diseases, prediction of adverse outcomes, and potential responses to treatment. Diastolic dysfunction is recognized as a fundamental substrate for the subsequent development of heart failure, including heart failure with preserved ejection fraction (HFpEF).[1]Studies have consistently demonstrated that the presence and progression of diastolic dysfunction are associated with an increased risk of heart failure and overall cardiovascular events, highlighting its significance in predicting long-term implications for patient health and mortality.[18]Monitoring changes in diastolic function over time is vital for assessing disease progression and evaluating the effectiveness of therapeutic interventions. For instance, serial assessments can reveal whether a patient’s diastolic function is deteriorating, remaining stable, or improving in response to pharmacological or lifestyle modifications. This dynamic assessment aids in adjusting treatment strategies to optimize patient care, potentially slowing disease progression and improving patient outcomes. The ability to predict outcomes and track disease evolution makes left ventricular diastolic function a critical metric in guiding clinical decisions and managing chronic cardiovascular conditions.[4]
Associations with Comorbidities and Therapeutic Implications
Section titled “Associations with Comorbidities and Therapeutic Implications”Left ventricular diastolic function is intimately linked with various comorbidities, revealing overlapping phenotypes and syndromic presentations that necessitate comprehensive management strategies. Conditions such as hypertension and diabetes are well-established risk factors for diastolic dysfunction, with studies showing significant associations between diabetes and impaired diastolic function traits.[1]Glycemic control, for example, has been shown to impact left ventricular diastolic function in patients with type 1 diabetes mellitus, underscoring the interconnectedness of metabolic health and cardiac mechanics.[25]Furthermore, diastolic function traits have been associated with heart failure, cardiomyopathy, and dilated cardiomyopathy, suggesting a broad role in the spectrum of cardiac diseases.[1]Understanding these associations is crucial for implementing targeted prevention strategies and selecting appropriate treatments. For instance, managing hypertension and diabetes effectively can help prevent or ameliorate diastolic dysfunction. The relationship between left atrial function and right ventricular function also emphasizes their functional interdependence, suggesting that interventions targeting one chamber may have ripple effects on others.[1]By integrating insights from left ventricular diastolic function assessments with a patient’s comorbidity profile, clinicians can develop more holistic and personalized treatment plans, including lifestyle modifications, medication adjustments, and closer monitoring, to reduce complications and improve overall prognosis.[28]
Frequently Asked Questions About Left Ventricular Diastolic Function
Section titled “Frequently Asked Questions About Left Ventricular Diastolic Function”These questions address the most important and specific aspects of left ventricular diastolic function based on current genetic research.
1. My parents have heart issues; will my heart struggle to relax too?
Section titled “1. My parents have heart issues; will my heart struggle to relax too?”Yes, there’s a significant genetic component to how well your heart relaxes and fills with blood. Research shows that inherited genetic differences can explain a notable proportion of the variation in specific heart relaxation traits, like up to 12-21% for certain measurements. So, a family history can indicate a higher predisposition for you.
2. Why do some people have healthy hearts despite unhealthy habits?
Section titled “2. Why do some people have healthy hearts despite unhealthy habits?”Genetics play a crucial role in individual differences. While environmental factors like habits are important, some people may have genetic variations that offer a degree of protection or influence their cardiac function differently. These genetic variants often have small individual effects, but their collective impact can contribute to overall heart health.
3. Can my diet or exercise really improve how my heart relaxes?
Section titled “3. Can my diet or exercise really improve how my heart relaxes?”Absolutely. Left ventricular diastolic function is influenced by both genetic and environmental factors. While your genes set a baseline, lifestyle choices like diet and exercise are powerful environmental factors that can significantly impact your cardiovascular health and improve how effectively your heart relaxes and fills.
4. Does my heart’s ability to relax just naturally get worse with age?
Section titled “4. Does my heart’s ability to relax just naturally get worse with age?”While aging is a factor in cardiovascular health, the progression of your heart’s ability to relax is also influenced by your genetic makeup. Diastolic function is a complex trait, meaning both your inherited genes and your lifestyle choices throughout your life contribute to how your heart maintains its relaxation capacity over time.
5. Does my ethnic background change my risk for heart relaxation problems?
Section titled “5. Does my ethnic background change my risk for heart relaxation problems?”Yes, your ethnic background can influence your risk. Most large-scale genetic studies have focused primarily on individuals of European ancestry. This means that the specific genetic risk factors identified may not be fully generalizable to populations of other ancestries, highlighting the need for more diverse research to understand these differences.
6. I feel healthy, but could my heart already have relaxation issues?
Section titled “6. I feel healthy, but could my heart already have relaxation issues?”Yes, it’s possible to have “asymptomatic left ventricular diastolic dysfunction.” This means your heart’s ability to relax might be impaired without you experiencing any noticeable symptoms. Early identification of these issues is clinically vital because it can be a precursor to more serious conditions like heart failure.
7. Does constant stress make my heart less able to relax properly?
Section titled “7. Does constant stress make my heart less able to relax properly?”While the article focuses on genetics, constant stress is a known environmental factor that impacts overall cardiovascular health. Your genetic makeup can influence how your body and heart respond to stress, potentially affecting various aspects of heart function, including its ability to relax effectively over time.
8. Could a genetic test tell me my risk for a “stiff” heart?
Section titled “8. Could a genetic test tell me my risk for a “stiff” heart?”Genetic studies have identified many variants associated with cardiac structure and function, including diastolic function. While a genetic test could indicate a predisposition based on these identified variants, it’s important to remember that these genetic influences often have small individual effects and are part of a larger picture that includes lifestyle and other factors.
9. If heart problems run in my family, can I actually prevent them?
Section titled “9. If heart problems run in my family, can I actually prevent them?”Yes, you absolutely can take proactive steps. Even with a family history, early identification of any impaired diastolic function allows for timely interventions and management strategies. Lifestyle modifications and medical care can significantly impact your outcomes and help mitigate the genetic predisposition.
10. Why do doctors measure how my heart fills with blood?
Section titled “10. Why do doctors measure how my heart fills with blood?”Doctors measure how your heart fills with blood to assess its “diastolic function,” which is critical for overall heart health. This helps them understand if your heart muscle is relaxing effectively to allow proper filling. These measurements are key for diagnosing issues like diastolic dysfunction, which can be an early sign of heart failure.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
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[3] Pirruccello, J. P., et al. “Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy.”Nat Commun, 2020.
[4] Nagueh, S. F. “Left ventricular diastolic function: Understanding pathophysiology, diagnosis, and prognosis with echocardiography.”JACC Cardiovasc Imaging, vol. 13, 2020, pp. 228–244.
[5] Sohn, D. W. “Heart failure due to abnormal filling function of the heart.”J Cardiol, vol. 57, no. 2, 2011, pp. 148–159.
[6] Gabriel, R. S., and A. L. Klein. “Modern evaluation of left ventricular diastolic function using Doppler echocardiography.”Curr Cardiol Rep, vol. 11, no. 3, 2009, pp. 231-238.
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[8] Tadros, R., et al. “Large-scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy.”Nat Genet, 2024.
[9] Shah, S. J., et al. “Phenotypic spectrum of heart failure with preserved ejection fraction.”Heart Fail Clin, vol. 10, no. 3, 2014, pp. 407–418.
[10] Devereux, Richard B., et al. “Standardization of M-mode echocardiographic left ventricular anatomic measurements.” J Am Coll Cardiol, vol. 4, no. 6, 1984b, pp. 1222-1230.
[11] Onishi, Takeshi, et al. “Global longitudinal strain and global circumferential strain by speckle-tracking echocardiography and feature-tracking cardiac magnetic resonance imaging: comparison with left ventricular ejection fraction.” J Am Soc Echocardiogr, vol. 28, no. 5, 2015, pp. 587-596.
[12] Borbély, A., et al. “Cardiomyocyte stiffness in diastolic heart failure.”Circulation, vol. 111, 2005, pp. 774–781.
[13] Redfield, Margaret M., et al. “Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic.”JAMA, vol. 289, no. 2, 2003, pp. 194-202.
[14] Playford, D., et al. “Diastolic dysfunction and mortality in 436 360 men and women: the National Echo Database Australia (NEDA).”Eur Heart J Cardiovasc Imaging, 2020.
[15] Chiao, Yen-An, and Peter S. Rabinovitch. “The aging heart.”Cold Spring Harb Perspect Med, vol. 5, no. 10, 2015, a025148-a025148.
[16] Hung, C-L., et al. “Age- and sex-related influences on left ventricular mechanics in elderly individuals free of prevalent heart failure.”Circ Cardiovasc Imaging, vol. 10, e004510, 2017.
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