
==== Front
Ann Med
Ann Med
Annals of Medicine
0785-3890
1365-2060
Taylor & Francis

39301864
10.1080/07853890.2024.2405080
2405080
Version of Record
Review Article
Cardiology & Cardiovascular Disorders
Progress in diagnosis and treatment of hypertension combined with left ventricular hypertrophy
Y. Han et al.
Annals of Medicine
Han Yongjin a*
Li Yanqiu b*
Wu Zhen b*
Pei Ying b*
Lu Saien a*
https://orcid.org/0009-0005-5090-4475
Yu Haijie a*
https://orcid.org/0000-0002-1854-0385
Sun Yingxian a
https://orcid.org/0000-0003-4794-5514
Zhang Xueyao a
a Department of Cardiology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
b Department of Cardiology, Yixian People’s Hospital, Jinzhou, Liaoning Province, China
* Yongjin Han, Yanqiu Li, Zhen Wu, Ying Pei, Saien Lu, and Haijie Yu contributed equally to this work.

CONTACT Xueyao Zhang zhangxueyao12@163.com Department of Cardiology, First Hospital of China Medical University, No 155, Nanjing North Street, Heping District, Shenyang 110001, Liaoning Province, China.
20 9 2024
2024
20 9 2024
56 1 240508030 5 2024
6 9 2024
9 9 2024
KnowledgeWorks Global Ltd.20 9 2024
published online in a building issue20 9 2024
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
2024
The Author(s)
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

Abstract

Background

Hypertension, a worldwide cardiovascular issue, is known to result in significant damage to the left ventricle. Left ventricular hypertrophy refers to an increase in ventricular mass, which is not only the primary independent risk factor for cardiovascular disease onset but also independently related to the risk of death.

Objectives

We sought to synthesize the existing literature on the occurrence and correlation between hypertension and left ventricular hypertrophy and the progress.

Methods

A scoping review was performed based on the methodological framework developed by Arksey & O’Malley. Search in the Pubmed database with no language restrictions, as of September 1, 2024.

Results

Of the 8110 articles retrieved, 110 were finally included. The selected articles were published between 1987 and 2024, with 55.5% (61/110) of the studies in the last five years and 14.5% (16/110) of 2024. The studies covered diagnosis, epidemiology, pathophysiology, prognosis, and treatment of hypertension with left ventricular hypertrophy.

Conclusion

The literature reviewed suggests that studies on hypertension combined with left ventricular hypertrophy covered a variety of clinical progress, especially the clinical trial results of some new drugs that may bring great hope for treatment.

KEY MESSAGES

Continuous development of 3D echocardiographic technology may provide more accurate measurements; however, studies with the aim of establishing standard reference values remain in exploratory stages.

The field of metabolomics offers a promising approach for studying biomarkers by detecting changes in metabolites associated with physiological or pathological processes induced by diseases. This avenue of research holds potential for the early diagnosis and assessment of LVH.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors and metformin are initially indicated for conditions other than left ventricular hypertrophy (LVH); however, emerging evidence suggests that these medications may possess potential clinical value in reversing LVH.

Keywords

Left ventricular hypertrophy
hypertension
diagnostic evaluation
Scientific Research Fund of Liaoning Provincial Education Department, China JYTQN2023022 This work was supported by the Scientific Research Fund of Liaoning Provincial Education Department, China (grant number JYTQN2023022). The funding agency had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the article for publication.
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pmcIntroduction

Hypertension is the most significant controllable risk factor for the development and fatality of cardiovascular disease (CVD) [1] and causes left ventricle damage. Over 30% of patients with hypertension worldwide are estimated to have left ventricular hypertrophy (LVH), which severity correlates with high incidence and risk of death from CVD [2]. The 2018 European Society of Hypertension (ESH) Clinical Practice Management Guidelines for Hypertension define LVH as a critical element in the coronary artery risk assessment system, linked to the onset and progression of diastolic dysfunction [3]. Early detection and intervention of LVH are significant factors in the prevention and treatment of CVD. Therefore, this review focuses on the relationship between hypertension and LVH and details the progress in the diagnosis, pathophysiology, epidemiology, prognosis, and treatment of hypertension combined with LVH. The schematic diagram of the research progress related to LVH is shown in Figure 1.

Figure 1. Schematic diagram of research progress related to LVH. AI, artificial intelligence; ARB, angiotensin receptor blockers; CCB, calcium channel blockers; CVD, cardiovascular disease; ECG, electrocardiography; LVH, left ventricular hypertrophy; MRI, magnetic resonance imaging; RDN, renal denervation; SGLT2, sodium–glucose cotransporter 2; STE, speckle tracking echocardiography.

Progress in the diagnosis of LVH

Cardiac magnetic resonance imaging (MRI), echocardiography, and electrocardiography (ECG) are the main diagnostic techniques for evaluating changes in left ventricular geometry. Echocardiography and MRI are regarded as gold standard methods [4]; however, owing to the lack of cost-effective data, the American College of Cardiology/American Heart Association and other hypertension management guidelines have not yet recommended their regular use [5].

ECG diagnosis

The ECG standards for LVH recommended by the 2018 ESH/European Society of Cardiology (ESC) hypertension management guidelines [3] include:Sokolow-Lyon standard [6]: SV1 + RV5 or SV1 + RV6 > 3.5 mV

aVL standard [3]: RaVL ≥1.1 mV

Cornell standard [6]: SV3 + RaVL (Cornell voltage) >2.8 mV in males and >2.0 mV in females

Cornell product standard [7]: (Cornell voltage × QRS duration) >244 mV × ms

Other diagnostic criteria include the Dalfó standard, Peguero-Lo-Presti standard (SD + SV4), RLI + SV4 standard, Romhilt Estes standard, and Seamens’ Sign, among others. The diagnostic efficacy are shown in Table 1.

Table 1. Comparison of ECG diagnostic criteria for LVH.

Standard	Diagnostic requirement	Specificity (%)	Sensitivity (%)	Population	
Male	Female	Male	Female	
Sokolow-Lyon	SV1+RV5 or SV1+RV6 > 3.5 mV;	78	27	Young stroke populations in Africa [8]	
Cornell	SV3+RaVL > 2.8 mV	SV3+RaVL > 2.0 mV	52	32	Young stroke populations in Africa [8]	
Cornell product	Cornell voltage × QRS duration > 244 mV × ms	>70	55.2	56.9	Hospitalized patients with hypertension in China [9]	
Dalfó	SV3+RaVL > 1.6 mV	SV3+RaVL >1.4mV	71.3	56	Northern Mexico [10]	
RLI+SV4	RLI+SV4 ≥ 1.6 mV	RLI+SV4 ≥ 1.4 mV	89	39	Japanese residents’ study [11]	
Peguero-Lo-Presti	SD + SV4 ≥ 2.6 mV	SD + SV4 ≥ 2.1 mV	>70	65.5	81	Hospitalized patients with hypertension in China [9]	
ECG, electrocardiography; LVH, left ventricular hypertroph.

The actual predictive performance of various ECG-LVH standards varies significantly among different races or regions; in a study of 432 patients in northern Mexico, the Dalfó standard demonstrated a relatively optimal predictive performance for LVH [10], with a specificity of 71.3%, sensitivity of 56%, positive predictive value of 62.9%, negative predictive value of 65%, and diagnostic accuracy (95% confidence interval [CI]) of 64.1% (59.5–68.6%). However, Matuja et al. studied the practical application of various ECG diagnostic standards for young stroke populations in Africa [8] and found that the specificity and sensitivity of the Sokolow-Lyon for diagnosing LVH were 78% and 27%, respectively, and the sensitivity and specificity of the Cornell standard were 32% and 52%, respectively. A Japanese study (n = 866) [11] found that the ‘RLI + SV4’ method showed a good predictive performance (area under the curve [AUC] = 0.76), higher than those of the Sokolow-Lyon (AUC = 0.61) and ‘SD + SV4’ standards (the deepest S wave in any lead and the S wave in lead V4) (AUC = 0.63). Furthermore, the Cornell standard demonstrated an AUC of 0.74, while the Cornell product standard showed an AUC of 0.76; a similar predictive performance was observed in the validation cohort. The cutoff value for the RLI + SV4 standard was 1.6 mV for males and 1.4 mV for females, with a diagnostic sensitivity of 39% and specificity of 89%. In comparison, the SD + SV4 standard showed a sensitivity of 21% and a specificity of 94%.

However, for a select population with hypertension, the predictive power of ECG-LVH may be less ideal. Among patients with hypertension who visited clinics in Spain, a cross-sectional analysis showed that only approximately one quarter of LVH cases were detected using the ECG Cornell product criteria [12]. Recently, the newly proposed Peguero-Lo-Presti standard improved the sensitivity and accuracy of LVH diagnosis in hospitalized patients with hypertension in China [13]. The sensitivity for LVH diagnosis was 65.5% for males and 81% for females, whereas the Cornell product standard had a sensitivity of 55.2% for males and 56.9% for females. The specificity of both groups was higher than 70%, with no significant differences between the two [9]. Consequently, the value of ECG-LVH standards for the LVH cases is relatively inconsistent, and there is currently no consensus on which ECG standard is optimal.

Echocardiography

Two-dimensional (2D) echocardiography is the most used diagnostic method for evaluating left ventricular geometry. Left ventricular mass (LVM) is associated with body size, age, sex, ethnicity, and physical activity levels [14]. The mass index of the left ventricle and body surface area allow for comparisons between individuals with different body types. However, in individuals with extreme obesity, the height index is more suitable than the mass index of the body surface area [15]. The 2015 guidelines of the American Society for Echocardiography/European Association for Cardiovascular Imaging [16] defined the diagnosis of LVH based on the left ventricular mass index (LVMI) calculated using body surface area as >95 g/m2 for females and >115 g/m2 for males; the truncation values of the 2D formula method are >88 g/m2 for females and >102 g/m2 for males. Compared with 2D echocardiography, three-dimensional (3D) echocardiography offers more precise and consistent measurements of left ventricular volume and mass, free from geometric modeling constraints, and enables the assessment of non-pre-shortened imaging [17]. However, current research using 3D echocardiography technology is relatively scarce, and normal reference cutoff values for 3D echocardiography have not been defined.

Speckle tracking echocardiography (STE)

Patients with hypertension and aortic stenosis are prone to developing LVH, although LVH may also occur secondary to diseases such as athletic heart disease, hereditary cardiomyopathy, myocardial amyloidosis, and Fabry’s disease, among others. STE technology helps differentiate the etiology of LVH and offers crucial prognostic information for patients with heart failure with preserved LVH and ejection fraction. STE measures strain and strain rate by tracking the movement of specific points throughout the cardiac cycle using 2D and 3D echocardiography, allowing for measurements in three spatial directions: longitudinal, radial, and circumferential. STE technology can also be used to evaluate torsion and untwisting of the left ventricular myocardium. Longitudinal total stress evaluated using 2D ultrasound STE is a sensitive indicator of small early abnormalities in the left ventricular myocardium, which is helpful for the prognosis of various heart diseases and is superior to traditional echocardiography indicators. Therefore, this evaluation has positive diagnostic significance for left ventricular remodeling associated with early hypertension [18]. Current research has confirmed the effectiveness of 2D STE in distinguishing between athletic heart disease and hypertrophic cardiomyopathy [19].

Cardiac MRI

Cardiac MRI is considered the gold standard for ventricular evaluation and quantification [20]. This technology can provide detailed imaging information of the endocardium and epicardium [21], regardless of the geometrics of the left ventricular morphology. The unique capabilities of cardiac MRI contribute to the identification of tissue characteristics [22,23]. Furthermore, cardiac MRI can identify and measure myocardial fibrosis through late gadolinium enhancement on T1-weighted sequences, aiding in determining the underlying cause. In patients with LVH, MRI allows for precise assessment of the severity and distribution of hypertrophy, evaluation of ventricular function, and tissue characterization. The information obtained from cardiac MRI enables the identification of the etiology of LVH and may aid in predicting prognosis and selecting appropriate therapy [24]. However, the availability, economic cost, time consumption, and patient tolerance of cardiac MRI currently limit its widespread use [20].

Exploration of novel LVH diagnostic biomarkers

Research in lipomics revealed that the plasma aliphatic lipid chain -CH2-/-CH3 ratio can be utilized as a LVH diagnostic biomarker. The sensitivity and specificity for distinguishing LVH (AUC = 0.703) were 52.08% and 85.42%, respectively [25]. Recent transcriptomic studies found that circulating levels of miRNAs such as let-7c, miR-451, and miR-145-5p are associated with LVH in patients with hypertension, suggesting their potential as biomarkers or that they might be involved in the remodeling of the left ventricle due to hypertension [26]. Weighted gene co-expression network analysis of RNA sequencing data from a mouse model of angiotensin II-induced hypertension with concomitant LVH, combined with multiple machine learning strategies, identified six potential hub immune-related genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict the diagnosis of hypertensive LVH [27]. The Bogalusa Heart Study included patients aged between 33.6 and 57.5 years, 34.98% of whom were African American and 57.41% of whom were female. The study revealed a correlation between LVMI and pseudouridine and N-methionine levels, indicating that mitochondrial-derived metabolites could serve as early biomarkers for LVH and subclinical heart failure [28]. Some studies also found that circulating osteopontin is an independent risk factor for LVH in patients with primary hypertension [29]. The latest study used flow cytometry and enzyme-linked immunosorbent assays to demonstrate significantly decreased circulating CD4+, CD25+, Foxp3+, and regulatory T lymphocytes (Tregs) in patients with hypertensive LVH. Interleukin (IL)-6, IL-10, and transforming growth factor-β1 (TGF-β1) correlate with LVH in patients with hypertension [30]. Additionally, serum TGF-β1 influenced hemodynamics, stimulated the production of endothelin, or activated the renin-angiotensin-aldosterone system (RAAS), thereby promoting LVH. It was identified as an important molecular marker for predicting LVH in children with primary hypertension [31]. Elevated levels of soluble suppression of tumorigenicity-2 (sST2), which reflected myocardial fibrosis and hypertrophy, were indicative of adverse clinical outcomes in heart failure and coronary artery disease. Recent studies showed that high sST2 levels were closely associated with LVH in patients with primary hypertension, making sST2 a potential new biomarker for the diagnosis and risk assessment of hypertensive heart disease [32]. Additionally, the systemic immune-inflammation index independently predicted LVH in patients with hypertension and may serve as a simple preliminary indicator for determining LVH occurrence [33].

Exploration of novel LVH diagnostic technologies and methods

The emergence of new technologies and methods can also facilitate the diagnosis of LVH. For instance, positron emission tomography offers a clinically valuable approach by combining quantitative myocardial perfusion evaluation, which may detect LVH with high accuracy and precision [34]. Additionally, although artificial intelligence (AI) diagnostic methods based on wearable devices are still in the exploratory stage, there have been notable advancements. A recent deep learning predictive model, developed using single-lead ECG data from wearable devices, has shown potential in identifying and diagnosing LVH, with an AUC of 0.797. Remarkably, this model’s predictive performance for LVH may even surpass or be comparable to that of cardiologists interpreting 12-lead ECGs [35]. Furthermore, wearable devices, such as smartwatches, can continuously and dynamically capture single-lead ECG signals, which can then be used in conjunction with unseen PTB-XL PhysioNet data to generate a 12-lead ECG signal. The generated ECG signals can be classified and identified for LVH using a ResNet classification model, which may potentially outperform the real-time detection capabilities of traditional 12-lead ECGs [36]. In a study by Xu et al. an artificial intelligence diagnosis system was presented based on image omics technology. The randomized controlled trial was conducted in 299 patients and proposed an intelligent identification system for LVH etiology classification based on routine transthoracic echocardiography video images, which displayed good diagnostic performance for LVH (sensitivity 99.8% and specificity 98.8%) [37]. The Kokubo T study demonstrated deep learning as a valuable tool for identifying left ventricular dilatation and LVH using 12-lead ECGs. The deep learning model achieved an AUC of 0.784 (95% CI, 0.777–0.791) for detecting LVH, significantly higher than those obtained with logistic regression and random forest methods using traditional ECG criteria (p < 0.001) [38]. Studies have also shown that utilizing a two-dimensional convolutional neural network can improve ECG diagnosis of LVH, achieving an AUC of up to 0.921 [39]. Although some research suggests that AI methods generally enhance sensitivity, compared with classic ECG standards, they often fall short in improving specificity [40]. However, from an AI-based diagnostic perspective, most studies confirm that AI can significantly enhance the diagnostic accuracy of ECG for LVH and address the limitations of other detection devices in identifying early-onset LVH [41,42], including in specialized populations, such as pediatric patients [43], where development-related challenges may hinder accurate diagnosis.

Epidemiology

LVH is a physiological response to many changeable and unchangeable risk factors, including age, genetics, diabetes, hypertension, obesity, chronic kidney disease, a sedentary lifestyle, obstructive sleep apnea, and dietary salt intake [44]. The prevalence of hypertension combined with LVH depends on differences in the limited population studied, imaging modality used, and chosen diagnostic definition method. In a natural population without screening, LVH manifesting on ECG is relatively rare. The recent Atherosclerosis Risk in Communities (ARIC) study found that only 5.2% of the study participants had LVH [45]. A cross-sectional analysis of the natural population of rural communities in Thailand suggested an LVH prevalence of 6.6% [46].The proportion of individuals with hypertension diagnosed with LVH based on ECG was relatively high in the Systolic Blood Pressure Intervention Trial (SPRINT) trial [47] and an Italian study (7.4% and 13.9%, respectively) [48]. A Brazilian cohort study revealed that 31.7% of middle-aged and older adult individuals had hypertension [49]. Ultrasonography detected LVH in 37% of low-risk hypertension patients who had no signs of LVH on an ECG [50]. A meta-analysis of 30 studies involving 37,700 participants found that 36%–41% of those with hypertension had echocardiographic LVH. In high-risk hypertension patients, such as those with severe or refractory hypertension or a history of diabetes or cardiovascular disease, the incidence of LVH ranges from approximately 58% to 77% [51]. A prospective cohort study of 6,105 individuals, followed for a median of 14 years, revealed that hypertension led to a 2.5-fold higher risk of ECG-diagnosed LVH. Moreover, each 19-mmHg increase in systolic blood pressure raised the risk by 49% [52]. A recent meta-analysis of 38 articles evaluated the increased risk of LVH in children with hypertension (diagnosed through ambulatory blood pressure monitoring) and found that those with hypertension had an increased risk of LVH (odds ratio [OR], 4.69 [95% CI: 2.69–8.19]) and elevated LVMI (pooled difference, 5.13 g/m2; [95% CI: 3.78–6.49]) [53].

Prehypertension is also connected to LVH. A South Korean study with 52,111 participants found a fully adjusted OR for LVH and remodeling of 1.65 (95% CI: 1.45–1.87) for prehypertension, 2.85 (95% CI: 2.35–3.43) for new-onset hypertension, 2.02 (95% CI: 1.74–2.34) for controlled hypertension, and 3.31 (95% CI: 2.68–4.07) for uncontrolled hypertension [54]. Cuspidi et al. reported that the incidence of LVH in patients with normal blood pressure, prehypertension, and hypertension were 9%, 23.2%, and 36.5%, respectively. After using the LVMI to identify LVH, obesity, blood sugar, creatinine, total cholesterol, and antihypertensive drugs were managed over time during follow-up. Patients who progressed from prehypertension to sustained hypertension and those with sustained prehypertension showed a significantly increased risk of newly developed LVH compared with those with sustained ideal blood pressure (OR: 4.21 and 1.89, respectively) [44]. These findings indicate that early active treatment of hypertension, and even early intervention in prehypertension, is of great significance in preventing target organ damage such as LVH.

The presence of other comorbidities significantly elevates the risk of hypertension combined with LVH. For instance, insulin resistance is positively associated with increased left ventricular mass and relative wall thickness. Palmieri et al. reported a higher LVH prevalence in patients with both diabetes and hypertension than in those without [55]. A prospective study involving 1,160 participants found that metabolic syndrome can increase the risk of LVH by 2.4 times in patients with hypertension [56]. Furthermore, hyperhomocysteinemia independently contributes to LVH, and when combined with metabolic syndrome, the risk of LVH may be further elevated [57]. Consequently, the incidence of LVH is likely higher in patients with hypertension and additional comorbidities.

Pathophysiology

LVH is a form of myocardial remodeling characterized by ventricular wall thickening and increased myocardial mass. Hypertension-induced LVH involves intricate interactions between myocardial cells and non-myocardial cells, such as endothelial cells and fibroblasts, as well as the inflammatory immune system and endothelial dysfunction [58]. Stress induces mechanical stretching, which activates intracellular signaling cascades, resulting in gene expression and synthesis of proteins such as actin and myosin. Under pressure overload, left ventricular wall stress is reduced by enlarging myocardial cells in parallel. This adaptive response is driven by various neurohumoral mechanisms, including the expression of catecholamines, angiotensin II, and noncardiac growth factors [59]. The endogenous or exogenous elevation of plasma angiotensin II is widely recognized to be associated with acute myocardial cell necrosis and subsequent microscopic scar formation, leading to left ventricular remodeling [60]. At the same time, activation of the RAAS promotes vasoconstriction, ischemia, cell apoptosis, and fibrosis [61]. Furthermore, endothelial dysfunction is likely involved in the regulation of cardiac load, as impaired flow-mediated vasodilation under high shear stress has been linked to increased LVM across diverse populations [62]. Previous studies have also confirmed the association between endothelial dysfunction and left ventricular diastolic stiffness by measuring the reactive hyperemia index [63]. Some studies have found that endothelial damage or dysfunction may precede the onset of LVH, regardless of the clinical severity of hypertension. The elevation in circulating endothelial cells and their impaired regeneration play a crucial role in the development of LVH [64].

The immune system plays a crucial role in the pathogenesis of hypertension and hypertension-induced damage to terminal organs. In clinical trials, adaptive immune imbalances and elevated levels of pro-inflammatory markers have been shown to promote hypertension progression and target organ damage [65]. The upregulation of mechanical stretching and inflammatory responses can trigger the differentiation of fibroblasts into myofibroblasts, which leads to the formation of myocardial fibrosis as the production of type I collagen and type II fibers increases.

Another important pathophysiological connection between hypertension and LVH is the upregulation of the activation of the sympathetic nervous system [66]. The chronic activation of the sympathetic nervous system is a key component of myocardial hypertrophy and fibrosis. In a spontaneously hypertensive rat model, sympathetic nerve resection resulted in decreased blood pressure and normalization of the left ventricular mass [67].

Clinical prognosis

LVH and CVD

The Early Framingham Heart Study found that diagnosing LVH with echocardiography was associated with higher rates of both CVD incidence and mortality, as well as all-cause mortality [4]. Similarly, the Antihypertensive Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study showed that baseline LVH (using the Cornell product or Sokolov-Lyon criteria) increased the risk of the CVD endpoint by 45%–140%. During antihypertensive treatment, sustained presentation or progression of LVH on ECG is significantly associated with an increased risk of cardiovascular endpoints and all-cause mortality [68]. The effect of LVH on the prognosis of CVD in different ethnic groups has also been reported. A subgroup analysis report in the ARIC prospective cohort study stated that LVH is a strong predictor of CVD among African Americans, and its impact on CVD is similar in both males and females [69]. A meta-analysis of four randomized controlled trials comprising 20,747 participants showed that in patients with high-risk factors for CVD, intensified antihypertensive therapy resulted in significant regression of LVH (OR: 0.68; 95% CI: 0.52–0.88) [70].

LVH and cardiovascular and all-cause mortality

Some studies have shown that left ventricular geometric abnormalities are associated with the risk of sudden cardiac death (SCD) [71]. The Framingham Heart Study included 3,661 participants aged >40 years and evaluated the relationship between SCD and both left ventricular mass and LVH. During an average follow-up of 14 years, the risk of SCD was significantly higher in patients with LVH than in those without LVH (adjusted hazard ratio [HR]: 2.2, 95% CI: 1.2–3.8). This was confirmed by Cox regression in the recent Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) Study, which was based on a large prospective English cohort (age ≥45 years). In this study, LVH was independently associated with all-cause mortality (HR: 1.38, 95% CI: 1.01–1.88) and cardiovascular mortality (HR: 2.64, 95% CI: 1.21–3.73); moreover, for every 50 g/m2 increase in left ventricular mass, the risk of SCD increased by 50% [72]. Other studies have shown that ECG-LVH is associated with the risk of SCD [61] and is an independent risk factor of SCD, regardless of its etiology, degree of symptoms, and type (concentric/eccentric) [73]. It is worth noting that regardless of the diagnostic method (ECG or color Doppler), the risk of cardiac arrest will be significantly increased in patients with LVH [74].

LVH and heart failure

The relevant study on the cardiovascular outcomes of losartan intervention, namely the Losartan Intervention for Endpoint reduction in hypertension (LIFE), showed that patients with LVH (ECG diagnostic criteria) have a 5-year risk of developing chronic heart failure that is more than three times higher than that of those without LVH. Furthermore, patients with LVH have a 4-fold higher risk of heart failure-related death than those without LVH [75].

LVH and myocardial ischemia

LVH frequently leads to myocardial ischemia, likely due to several factors. First, the increase in LVM associated with LVH results in a higher oxygen demand. However, because the number and diameter of coronary vessels do not increase proportionately, the oxygen supply to the myocardium becomes inadequate, leading to an imbalance between oxygen supply and demand [76]. Secondly, coronary microvascular dysfunction may contribute to this condition. This dysfunction increases resistance in the coronary microcirculation and can reduce coronary reserve, particularly during exercise or stress. Some studies suggest that, among patients with suspected stable coronary artery disease who do not have obstructive coronary artery disease, those with LVH are more prone to coronary microcirculation disorders [77]. In fact, LVH may even be an independent cause of myocardial ischemia [78]. Additionally, LVH is often accompanied by thickening and increased stiffness of the left ventricular wall, which can compress the subendocardial coronary vessels, further reducing myocardial blood supply, especially during diastole [79].

Moreover, LVH is associated with higher cardiovascular mortality after percutaneous coronary intervention. A Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction substudy found that LVH correlated with larger infarction areas, reduced myocardial salvage, increased microvascular obstruction, and lower left ventricular ejection fraction in patients with ST-elevation myocardial infarction [80].

LVH and arrhythmia

Using a random-effects model combined with an analysis of ten previous studies [81], Chatterjee et al. found that LVH was associated with the risk of arrhythmia. The incidence of supraventricular and ventricular arrhythmias in patients with LVH was 11.1% and 5.5%, respectively, and only 1.1% and 1.2%, respectively, in patients without LVH (p < 0.001). A cross-sectional study indicated that hypertension-induced LVH is linked to a higher risk of mortality and arrhythmia and found that 16.3% of patients with both hypertension and LVH experienced arrhythmia, with atrial fibrillation and premature ventricular complexes being the most common types [82].

However, some studies suggest that the high risk of ventricular arrhythmias in patients with hypertension combined with LVH may be attributed to a combination of coronary heart disease or electrolyte disorders, and there is confusion regarding its aetiology [83]. Verdecchia et al. studied the role of LVH in the occurrence of atrial fibrillation. Their study followed 2,482 patients with primary hypertension for 16 years: of these patients, 61 experienced atrial fibrillation (0.46/100 person-years) during the follow-up period. The analysis revealed that age and increased LVMI were independent predictors of atrial fibrillation. An increase of one standard deviation in LVMI led to a 20% increased risk of atrial fibrillation [84]. A cohort study of 4,942 patients with a median follow-up of 6.9 years found that patients with LVH detected using MRI had a higher risk of atrial fibrillation than those without LVH [85]. In addition, atrial fibrillation development in patients with LVH and hypertension is associated with an elevated risk of SCD [72].

LVH and cognitive decline

LVH, as a marker of target organ damage in hypertension, may help identify cognitive decline in older patients with hypertension. In a double-blind, randomized controlled study, ECG-LVH (according to the Cornell Product standard) was associated with an increased risk of cognitive decline [86]. Furthermore, LVMI has been shown to be directly related to reduced overall cortical thickness, increased cortical brain age, and accelerated brain aging, independent of the effects of blood pressure on the brain [87].

Treatment progress

The 1990 Framingham Heart Study demonstrated that reversing ECG-diagnosed LVH significantly reduced the incidence of CVD (OR: 0.46; 95% CI: 0.26–0.84) [88]. The LIFE study, a milestone trial in the early twenty first century, confirmed the responsiveness of LVH to antihypertensive therapy, the possibility of reversal, and the benefits regarding related cardiovascular events [89]. The Heart Outcomes Prevention Evaluation (HOPE) study found that ramipril’s effect on reducing LVH was independent of blood pressure changes and could improve CVD prognosis [90]. Recent studies have confirmed that enhanced blood pressure reduction has a beneficial effect on the prognosis of CVD in patients with LVH [91]. A recent meta-analysis indicates that intensive blood pressure reduction results in a significant 15% decrease in the risk of LVH, with individuals with CVD benefitting the most from a 39% reduction in LVH risk. Furthermore, those with baseline LVH experienced a 32% regression rate with intensive blood pressure lowering [70]. The most recent SPRINT (8,820 participants) revealed that targeting a < 120 mmHg systolic blood pressure resulted in a lower incidence of LVH among hypertension patients without diabetes compared with targeting a 140 mmHg systolic blood pressure. Moreover, this intensive blood pressure control led to a higher rate of LVH reversal in patients who already had LVH [47]. Patients with baseline malignant LVH randomly assigned to the intensive antihypertensive group experienced a 4.4% reduction in absolute risk of SCD over 4 years (95% CI: 5.2%–13.9%). Additionally, intensive reduction in systolic blood pressure decreased the incidence of malignant LVH at two years (OR: 0.44; 95% CI: 0.30–0.63) [92]. Moreover, controlling blood pressure rhythm is crucial during intensive blood pressure lowering. The latest population study from Japan indicates that, among patients with diabetes, those who do not control nighttime blood pressure have a 3.1 times higher risk of developing LVH, compared with those who effectively manage nighttime blood pressure [93].

Interestingly, the rate at which LVM reverses following antihypertensive treatment varies significantly across different study populations [94]. The predictive factors for sustained irreversible LVH after antihypertensive therapy include older age, longer duration of hypertension, central obesity, kidney disease, higher body mass index, and poor blood pressure control [95]. Therefore, to avoid irreversible LVH, antihypertensive treatment should be initiated as soon as possible, and appropriate blood pressure targets should be achieved while addressing comorbidities, such as obesity. The STEP Trial found that in the older hypertensive population, a more intensive systolic blood pressure target of 110–130 mmHg was significantly associated with a reduced risk of new-onset LVH [96]. However, it is important to note that older patients with LVH may exhibit a heightened sensitivity to reductions in systolic blood pressure due to impaired myocardial microcirculation, potentially leading to an increased risk of adverse events. This phenomenon was observed over a 6-month follow-up period in a recent randomized controlled trial involving 13,803 participants. Older patients with LVH who achieved an average systolic blood pressure <130 mmHg had higher mortality rates related to cardiac events (HR: 1.98; 95% CI: 1.06–3.70; p = 0.032) and increased all-cause mortality (HR: 1.74; 95% CI: 1.17–2.60; p = 0.007) [97]. Therefore, for patients with LVH and different blood pressure levels or in different age groups, individualized or differentiated blood pressure targets need to be further explored; blindly pursuing low blood pressure to improve long-term cardiovascular prognosis should be avoided.

The 2018 ESH/ESC Hypertension Management Guidelines recommend a systolic blood pressure target of 120–130 mmHg for all patients with hypertension and LVH (evidence levels IA and IIA). The guidelines further recommend that RAAS inhibitors should be combined with standard calcium channel blockers and diuretic treatment [3]. A meta-analysis comprising 80 double-blind randomized controlled trials found significant differences in the efficacy of different drugs for LVH after adjustment for treatment time and changes in diastolic blood pressure (p = 0.004); angiotensin II receptor antagonists reduced LVH risk by 13%, calcium channel antagonists by 11%, angiotensin-converting enzyme inhibitors by 10%, diuretics by 8%, and β receptor blockers by 6% [98]. Among angiotensin receptor antagonists, a head-to-head study confirmed that olmesartan is superior to other angiotensin II receptor antagonists in lowering blood pressure and improving LVH due to its unique molecular structure and mechanism of action [99]. Furthermore, in a multicenter, double-blind randomized controlled trial involving patients with hypertension, Schmieder et al. reported that compared with olmesartan, sacubitril/valsartan significantly reduced LVM, which may explain its resulting superior CVD prognosis [100]. Cost-effectiveness studies of sacubitril/valsartan in hypertensive populations in Asia [101] and China [102] further confirmed its potential applicability in the treatment of hypertension. However, as the drug is currently only approved and used in Asia, more clinical trials are needed to ascertain its effectiveness in other populations. Recent research further confirmed that switching from other angiotensin II receptor antagonist medications to sacubitril/valsartan effectively reduced blood pressure in patients with resistant hypertension and further reversed ventricular remodeling, with observed improvements in hemodynamics [103]. Although human studies were limited, the latest animal experiments also validated these effects of sacubitril/valsartan. The dual inhibition of neprilysin and the angiotensin II type 1 receptor by sacubitril/valsartan led to a reduction in systolic blood pressure and prevented the progression of LVH, myocardial fibrosis, and both systolic and diastolic dysfunction [104]. In animal experiments, other drugs, such as fenofibrate, which are lipid-lowering agents, were shown to directly affect myocardial cells and counteract pressure overload-induced maladaptive cardiac remodeling. By regulating mediators of mitochondrial dynamics and autophagy, these drugs inhibited the progression of hypertension and reduced increases in LVM, relative wall thickness, and myocardial cell cross-sectional area [105]. However, further experimental research is needed before these findings can be applied clinically.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and biguanides are also commonly used to clinically reverse LVH. Various small trials, such as the DAPA-LVH, NCT0295691 studies, and EMPA-HEART, are currently in progress to evaluate whether the reversal of increased LVM can explain the reduction of CVD incidence and mortality following SGLT2 inhibitor treatment. SGLT2 inhibitors may reduce LVM through two main mechanisms: 1) their diuretic and natriuretic effects lower left ventricular wall stress and 2) their inhibition of sodium-hydrogen exchange in myocardial cells, which affects cardiac remodeling. Additionally, metformin could reverse LVH by improving fatty acid oxidation and decreasing oxidative stress [106]. Therefore, metformin may be a promising new treatment for preventing or improving LVH caused by chronic hypertension. A recent multicenter, open-label, prospective, interventional study confirmed the efficacy and safety of esaxerenone in hypertensive patients with LVH. The study found that, in addition to its effective antihypertensive effects, esaxerenone offers cardioprotective benefits, reducing LVMI by 8.5% after 24 weeks of treatment [107]. As the latest aldosterone receptor antagonist in the market, esaxerenone has consistently demonstrated blood pressure-lowering and LVH regression effects in hypertensive patients with LVH, regardless of whether it is used alone or in combination with other antihypertensive medications.

Regarding non-pharmacological treatments for hypertension with LVH, renal denervation (RDN) has shown promising results in treating resistant hypertension [108]. With advancements in technology, the latest 2024 ESC hypertension guidelines [109] have upgraded the recommendation level for RDN from III to IIb. Furthermore, recent meta-analyses indicated that RDN improved LVH, ejection fraction, and reduced LVMI, contributing to better ventricular remodeling in patients with resistant hypertension [110]. However, understanding the impact of RDN on left ventricular diastolic function still requires analysis with larger datasets.

Summary and outlook

LVH increases the risk of CVD and all-cause mortality, and ECG remains its primary diagnostic method. Continuous development of 3D echocardiographic technology may provide more accurate measurements; however, studies with the aim of establishing standard reference values remain in exploratory stages. Although cardiac MRI can help distinguish different types of LVH, it is expensive, time-consuming, and has poor accessibility. LVH can be reversed by lifestyle changes and antihypertensive therapy. RAAS inhibitors and calcium antagonists or diuretics are currently recommended treatment strategies for hypertension with LVH. Currently, numerous clinical trials are underway to investigate the effects of new drugs, such as SGLT2 inhibitors, on left ventricular mass in diabetes patients, both with and without hypertension. Esaxerenone, with its cardioprotective effects in addition to its antihypertensive properties, shows promise as a treatment option for patients with both hypertension and LVH. Early intervention targeting risk factors is vital for primary prevention of LVH caused by target organ damage in hypertension. In addition, early diagnosis and active individualized intervention for high-risk populations largely relies on cost-effective LVH diagnosis and evaluation methods. Due to the many shortcomings of the current initial ECG diagnostic methods, such as poor sensitivity and difficulty in combining LVH with obvious clinical symptoms, a missed diagnosis of LVH in clinical practice is highly probable. Therefore, establishing an economical and convenient predictive model for LVH is necessary. Furthermore, more reliable risk prediction indicators must be identified. The field of metabolomics is a promising approach for studying biomarkers, whereby changes in metabolites can be detected in the physiological or pathological processes caused by diseases; this avenue of discovery may help in the early diagnosis and evaluation of LVH. Furthermore, various new technologies based on deep learning and artificial intelligence can bring a new vision for the diagnosis of LVH, to better serve the majority of patients with LVH.

Authors contributions

Yongjin Han: Writing – original draft, Methodology, Visualization. Yanqiu Li: Writing – original draft, Investigation. Zhen Wu: Writing – original draft, Methodology. Ying Pei: Writing – original draft, Investigation. Saien Lu: Writing – original draft, Investigation. Haijie Yu: Writing – original draft, Investigation. Yingxian Sun: Supervision. Xueyao Zhang: Writing – review & editing, Conceptualization, Project administration. All the authors have read and approved the final version of the manuscript. All authors participated sufficiently in the study and agreed to be accountable for all aspects. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data in this review are from published public domains literature, so data sharing is not applicable here as no new data were created or analyzed in this study.
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