The differentiation between primary aldosteronism and essential hypertension in left ventricular remodeling before and after treatment: a follow-up study with quantitative stress cardiac magnetic resonance imaging

Introduction

Primary aldosteronism (PA), the most common form of secondary hypertension, is characterized by hypertension, suppressed renin activity, and autonomous aldosterone overproduction (1), accounting for approximately 5–10% of all cases of hypertension (2). An excess of aldosterone is associated with vascular and perivascular inflammation, oxidative stress, and fibrosis, promoting the development of the atherosclerotic plaque (3) and contributing to cardiac remodeling and dysfunction (4). This results in stiffening of the left ventricle with subsequent elevation in left ventricular end-diastolic pressure, potentially causing myocardial oxygen supply-demand mismatch and myocardial ischemia (5).

Autonomous aldosterone secretion level is relevant to left ventricular hypertrophy in patients with PA (6). Patients with PA have been reported to have worse left ventricular remodeling, including increased left ventricular mass and cardiac fibrosis, as compared to those with essential hypertension (EH) (7,8). Furthermore, patients with PA experience greater impairment in left ventricular diastolic function (9). In one study, the prevalence of cardiovascular complications was found to be significantly greater in patients with PA than in matched controls with EH (10). Although increased aldosterone levels lead to vascular stiffness, vasoconstriction, endothelial dysfunction, and cardiac fibrosis (11), the specific effects of excessive aldosterone on myocardial perfusion remain incompletely understood, especially as it pertains to microvascular function and perfusion reserve. Targeted surgical intervention or treatment with mineralocorticoid receptor antagonists (MRAs) can mitigate adverse aldosterone effects, improving blood pressure control and reducing left ventricular mass, myocardial fibrosis (12-14), and the risk of cardiovascular events and mortality (15). However, whether targeted interventions lead to improvement in myocardial perfusion reserve (MPR) and reduction in extracellular volume (ECV) fraction remains unclear.

Therefore, we aimed to conduct a prospective study to investigate the changes in cardiac remodeling following targeted treatment in patients with PA as compared with those of a control group of demographically similar patients with EH and to identify the independent clinical predictors of left ventricular remodeling. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-401/rc).

Methods

Study population and clinical evaluation

Patients diagnosed with PA along with age- and sex-matched patients with EH were enrolled between 2021 and 2023. This prospective study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of The Second Xiangya Hospital of Central South University (Approval No. 2010023815). Informed consent was obtained from all individual participants. Participants with a plasma aldosterone-to-renin ratio (ARR) greater than or equal to 30 ng/dL per ng/mL/h, an ARR ≥ 20 with plasma renin activity (PRA) <1 ng/mL/h, and a plasma aldosterone concentration ≥15 ng/dL underwent confirmatory tests. Confirmatory tests involved a saline infusion and/or a captopril challenge test. A postinfusion plasma aldosterone concentration of >10 ng/dL in the saline infusion test was the threshold for the diagnosis of PA, and a 30% suppression of plasma aldosterone following the captopril challenge test indicated PA. Patients with EH were included as controls and diagnosed based on a systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg after exclusion of other forms of secondary hypertension. The exclusion criteria were as follows: (I) atrial fibrillation, systolic left ventricular dysfunction, chronic heart failure, severe arrhythmia, myocardial infarction, cardiomyopathy, or valvular disorders; and (II) hypertension caused by other causes, such as renal hypertension, renal artery stenosis, Cushing syndrome, pheochromocytoma, or hypercortisolism. All patients with PA underwent adrenalectomy, while patients with EH received pharmacological therapy. The surgical approach for adrenalectomy was individualized based on tumor size, body shape, surgical history, wound considerations, and surgeon’s expertise. The surgery was performed via a transperitoneal or retroperitoneal approach and through either a single-port or multiport laparoscopic technique.

Magnetic resonance imaging (MRI) protocol

All participants underwent cardiac MRI with a 3-T scanner (MAGNETOM Skyra; Siemens Healthineers, Erlangen, Germany) equipped with 18-channel body coil scan protocols.

Myocardial perfusion imaging was performed during stress and at rest, with a steady-state free precession prebolus adenosine protocol being used to quantify absolute myocardial blood flow (MBF) (16). Heart rate was monitored via electrocardiography throughout imaging to correct related rest and stress MBF. Adenosine was infused at a rate of 140 µg/kg/min for 3 minutes. Five baseline frames were initially acquired with the administration of gadobutrol contrast agent (Bayer, Berlin, Germany), which was followed by an arterial input function (AIF) bolus injection (small dose 0.0075 mmol/kg) with a subsequent 20-mL saline injection and continuous stress AIF acquisition for a total of 60 frames under free breathing. Stress perfusion imaging commenced immediately thereafter under free breathing. After about five baseline frames, the main bolus (0.075 mmol/kg) was injected, with the contrast dose adjusted according to body weight through use of an online platform (https://www.circlecvi.com/qp-protocol/index.html). Adenosine infusion was discontinued after stress perfusion acquisition. After a 10-minute interval during which cine images were acquired, rest AIF acquisition was initiated under free breathing, followed by contrast agent injection with the same protocol described above.

Myocardial perfusion imaging was performed with a saturation recovery sequence based on a fast low-angle shot imaging sequence. Breath-hold cine imaging was performed with a segmented balanced steady-state free precession sequence. The detailed imaging parameters for these sequences were the same as those used in our previous work (17).

ECV fraction was derived from pre- and postcontrast T1 and blood pool values according to the following formula: ECV fraction = (1 – hematocrit) × [Δ(1/T1) myocardial/Δ(1/T1) blood flow] (18). Hematocrit was obtained on the same days as MRI. Pre- and postcontrast T1 mapping sequences involved a modified look-locker inversion recovery method (19,20).

Cardiac MRI analyses

All cardiac MR images were post-processed with cvi42 software (Circle Cardiovascular Imaging Inc., Calgary, AB, Canada). According to the American Heart Association left ventricular segmental analysis, the myocardium was divided into 16 segments (21). The software employed a fully automated framework incorporating a model constrained deconvolution technique to quantify pixel-wise MBF values in mL/min/g by processing time–signal intensity curves (16). The autosegmentations were manually adjusted when necessary. MPR was calculated as the stress MBF divided by the rest MBF (22). Representative images are shown in Figure 1. The left ventricular function parameters, including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), and left ventricular mass index (LVMi), were obtained.

Figure 1 Quantitative stress perfusion cardiovascular magnetic resonance imaging. (A,B) Rest MBF and stress MBF without color map in the short-axis mid-left ventricular slice. (C,D) Rest MBF and stress MBF with color map in the short-axis mid-left ventricular slice. (E-H) The bull’s-eye map of quantitative myocardial perfusion showing the rest MBF, stress MBF, and MPR. MBF, myocardial blood flow; MPR, myocardial perfusion reserve; rMPR, rest myocardial perfusion reserve.

Follow-up

At the 6-month postoperative follow-up, all patients underwent assessments including serum biochemistry and measurements of plasma aldosterone concentration and PRA, along with cardiac MRI. Corresponding clinical and imaging data were collected from hospital records.

Statistical analysis

The Kolmogorov-Smirnov test was employed to determine the normality of distribution of the continuous variables. Normally distributed continuous variables are expressed as the mean ± standard deviation, while continuous variables with a nonnormal distribution are expressed as the median and interquartile range (IQR). For comparisons between two groups, the Student’s t-test or the Mann-Whitney test was used for continuous variables, and the Chi-squared test was applied for categorical variables. Generalized estimating equations (GEEs) were applied to compare the changes in MRI variables with adjustments for age and body mass index (23). Relationships between continuous variables were assessed with the Pearson correlation coefficient or the Spearman rank correlation coefficient as appropriate. Linear regression analysis with stepwise elimination was applied to evaluate the relationship between the left ventricular remodeling parameters and physiological variables. PRA and ARR were log-transformed for the regression analysis, owing to their nonnormal distribution. Standardized beta and adjusted R² values were calculated. Intra- and interobserver variability was evaluated with intraclass correlation coefficient (ICC) analysis (two-way mixed model and absolute agreement between single measurements). Statistical analysis was performed with SPSS version 26.0. (IBM Corp., Armonk, NY, USA). P values <0.05 were considered statistically significant.

Results

Characteristics of patients with PA and EH

A total of 75 patients with PA and 75 EH controls were included (Table 1) in this study. Sex and age distribution were matched in the two groups. Patients with PA had higher plasma aldosterone concentration, higher ARR, and lower PRA compared to patients with EH. The baseline SBP and baseline DBP were similar in the groups.

Baseline LVEF, LVEDV, LVEDVi, LVESV, and LVESVi did not differ between patients with PA and EH. However, at the end of the follow-up, the median LVEDV [PA: 92 (IQR, 83–100) mL; EH: 97 (IQR, 87–101) mL, P=0.049], LVESV [PA: 41 (IQR, 38–47) mL; EH: 44 (IQR, 40–48) mL; P=0.041], and LVESVi [PA: 24.39 (IQR, 21.84–27.11) mL/m²; EH: 25.82 (IQR, 23.39–28.49) mL/m², P=0.043] were lower in the patients with PA. Initially, patients with PA exhibited a significantly higher median left ventricular mass [PA: 97 (IQR, 85–109) g; EH: 87 (IQR, 76–102) g; P=0.015] and mass index [PA: 54.40 (IQR, 47.22–65.22) g/m²; EH: 50.54 (IQR, 41.95–61.83) g/m²; P=0.009] compared to those with EH. At the end of the study, both left ventricular mass and mass index were observed to decrease significantly, with no significant differences between the PA and EH groups. Initially, there were no significant differences in median native T1 [PA: 1254 (IQR, 1218–1271) ms; EH: 1251 (IQR, 1218–1271) ms; P=0.728] and ECV fraction [PA: 26.9% (IQR, 26.7–27.7%); EH: 26.8% (IQR, 25.8–28.4%); P=0.118] between these two groups. Although there was a statistically significant difference in ECV fraction between the two groups after treatment [PA: 25.1% (IQR, 24.1–25.7%); EH: 25.3% (IQR, 25.1–27.2%); P<0.001], it was not substantial. Patients with PA had a lower MPR than did the patients with EH before treatment [PA: 1.9 (IQR, 1.8–1.9); EH: 2.3 (IQR, 2.1–2.4); P<0.001]. After treatment, the MPR in both the PA and EH groups increased significantly [PA: 2.3 (IQR, 2.3–2.4); EH: 2.4 (IQR, 2.2–2.5); P=0.822], culminating in no discernible difference between the two groups post-treatment.

In this cohort, patients with PA generally benefited from surgical treatment, which was characterized by effective blood pressure control or normalization, reduced aldosterone levels, correction of hypokalemia and associated symptoms (e.g., chest pain, fatigue, and palpitations), and improved cardiac function.

Cardiac MRI data before and after treatment of PA and EH

The differences in changes of MRI variables before and after treatment between patients with PA and patients with EH are compared in Table 2.

Patients with PA had a significant reduction in left ventricular mass, with a mean decrease of 17.96 g from pre- to posttreatment, while those in the EH group experienced a more modest decrease, averaging 6.84 g (Figure 2A). This pattern was mirrored in the LVMi, where patients with PA experienced an average reduction of 10.54 g/m², compared to a 4.02 g/m² decrease in the EH group. Of note, the improvement in MPR was more pronounced in patients with PA, with an increase of 0.49, surpassing the 0.13 increase seen in the EH controls (Figure 2B). Additionally, ECV fraction showed a significant decrease in both groups, with patients with PA exhibiting a 2.36% reduction, compared to a 1.21% reduction in patients with EH (Figure 2C). The LVEF also improved slightly in both groups, with patients with PA showing a 0.04% increase and patients with EH a 0.03% increase (Figure 2D). Both LVEDV and LVESV decreased significantly in patients with PA, with average reductions of 15.11 and 11.48 mL, respectively; in contrast, the EH group showed smaller reductions of 7.79 and 6.80 mL (Figure 2E,2F), respectively. The decreases in LVEDVi and LVESVi were also more significant in patients with PA, with reductions of 8.82 and 6.72 mL/m², respectively, while those in the EH group were 4.56 and 4.00 mL/m², respectively.

Figure 2 Left ventricular mass (A), MPR (B), ECV fraction (C), LVEF (D), LVEDV (E), and LVESV (F) in the pre- and posttreatment. The analyses were adjusted for age and body mass index. ECV, extracellular volume; EH, essential hypertension; GEE, generalized estimating equation; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; MPR, myocardial perfusion reserve; PA, primary aldosteronism.

Analysis of factors related to ventricular remodeling and myocardial perfusion

The relationship between logARR and baseline MRI variables in patients with PA are shown in Figure 3. After adjustments were made for age, sex, body mass index, and blood pressure, baseline logARR was associated with baseline LVMi, baseline MPR, and baseline ECV fraction, with correlation coefficients of 0.443 (P<0.001), –0.690 (P<0.001), and 0.574 (P<0.001), respectively. Moreover, the baseline LVMi was also associated with baseline MPR, with a correlation coefficient of –0.505 (P<0.001).

Figure 3 The relationship between baseline logARR and MRI variables in patients with PA (A-C). After adjustments for age, sex, body mass index, and blood pressure, baseline logARR was associated with baseline LVMi (A), MPR (B), and ECV fraction (C), respectively. ARR, plasma aldosterone-to-renin ratio; ECV, extracellular volume; LVMi, left ventricular mass index; MPR, myocardial perfusion reserve; MRI, magnetic resonance imaging; PA, primary aldosteronism.

Linear regression analysis was performed to determine the preoperative factors influencing postoperative left ventricular remodeling and myocardial perfusion, including mass, LVMi, LVEDVi, LVESVi, ECV fraction, and MPR (Table 3). We found that baseline logARR was independently associated with mass (beta =0.640; P<0.001), LVMi (beta =0.658; P<0.001), LVEDVi (beta =0.394; P<0.001), LVESVi (beta =0.535; P<0.001), ECV fraction (beta =0.503; P<0.001), and MPR (beta =–0.711; P<0.001), respectively. Additionally, the explanatory factor for the treatment-induced change in left ventricular remodeling and myocardial perfusion was change in logARR (Table 4).

Comparison between subtypes of PA

Of the 75 patients with PA, 36 individuals had a baseline LVEF of 0.5 or less, while 39 individuals had a baseline LVEF above 0.5. After treatment, only three individuals had an LVEF of 0.5 or less.

Clinical characteristics and MRI parameters were further stratified by LVEF in patients with PA (Table 5). Before treatment, there was no difference in age, height, weight, body mass index, aldosterone, or native T1. Patients with LVEF >0.5, as compared with patients with LVEF ≤0.5, had a lower median ARR [61.8 (IQR, 43.9–68.6) vs. 143.1 (IQR, 85.9–266.5) ng/dL per ng/mL/h; P<0.001], higher median PRA [0.61 (IQR, 0.39–0.86) vs. 0.27 (IQR, 0.13–0.40) ng/mL/h; P<0.001], lower median SBP [150 (IQR, 146–154) vs. 168 (IQR, 156–172) mm Hg; P<0.001], reduced median LVEDV [98 (IQR, 88–107) vs. 117 (IQR, 106–127) mL; P<0.001], reduced median LVESV [46 (IQR, 41–48) vs. 62 (IQR, 55–69) mL; P<0.001], decreased median LV mass [92 (IQR, 78–98) vs. 106 (IQR, 95–127) g; P<0.001], and lower median ECV [26.8 (IQR, 26.4–27.1) vs. 27.5 (IQR, 26.8–28.6) %; P=0.002]. Furthermore, those with higher LVEF, compared to the patients with a lower LVEF, also presented with an increased median rest MBF [1.2 (IQR, 1.2–1.2) vs. 1.1 (IQR, 1.1–1.2) mL/min/g; P=0.006] and improved median MPR [1.9 (IQR, 1.9–2.0) vs. 1.8 (IQR, 1.7–1.9); P<0.001].

Reproducibility analysis of MRI parameters

The analysis for the intra- and interobserver variability for MRI parameters is presented in Table 6. Excellent interobserver reproducibility (ICC >0.90) was demonstrated for all parameters, including left ventricular volumetric and functional parameters, MBF, and native T1.

Discussion

After an extensive literature search, we identified no prior studies that used quantitative stress perfusion cardiac MRI to assess changes in myocardial perfusion in patients with PA before and after targeted treatment (24-26). In this study, we used cardiac MRI to compare left ventricular remodeling and myocardial perfusion in patients with PA to those in patients with EH, who were matched for age and gender. Our findings revealed that patients with PA had elevated LVMi and reduced MPR compared to those with EH. Following the treatments, both groups demonstrated improvements in left ventricular remodeling and function. LogARR emerged as an independent risk factor for cardiac remodeling and dysfunction in patients with PA. Furthermore, the improvement in LVMi, MPR, and ECV were associated with the change in logARR.

Patients with PA in this study presented with typical characteristics of excessive aldosterone; specifically, they had a higher ARR and baseline LVMi than did patients with EH. This finding is consistent with several clinical studies that have confirmed the association of PA with a greater left ventricular mass, wall thickness, extracellular matrix expansion, and left atrial remodeling relative to patients with EH (7,27-29). The treatment of PA with removal of the aldosterone-overproducing adrenal gland or MRAs have been demonstrated to reverse these structural and functional abnormalities (6,12,24,30), which was also observed in our study. This reversal is likely associated with the reduction of aldosterone and elevation of renin posttreatment, as supported by the results indicated in our study.

Excessive aldosterone not only adversely damages the vasculature and cardiac muscle but also influences cardiovascular risk factors via various biochemical pathways, actively contributing to the progression of ischemic heart disease (31). Various epidemiological studies have revealed that individuals diagnosed with PA exhibit a notably increased prevalence of ischemic heart disease compared to those with EH (8,32). It has previously been demonstrated that patients with hypertension have reduced MPR (33). Moreover, in this study, we observed a further significant reduction in MPR values in the PA group compared to those in the EH group, suggesting that patients with PA experience a higher burden of ischemia and have more severe microvascular dysfunction. A previous study using single-photon emission computed tomography (SPECT) and echocardiography revealed that patients with PA exhibit exercise-induced myocardial ischemic defects more frequently than do those with EH (34). However, both SPECT and echocardiography have inherent limitations in assessing coronary microvascular dysfunction. SPECT is limited in quantification of MBF due to poor spatial and temporal resolution and is associated with high radiation exposure. Echocardiography is highly operator-dependent and can be hindered by artifacts, especially in patients with obesity or lung disease. In contrast, cardiac MRI has the added advantage over other modalities in that it enables the quantification of diffuse myocardial fibrosis, microvascular dysfunction, and cardiac remodeling.

MPR is affected by endothelial dysfunction and microcirculation status (35,36). Quantification of MPR represents a promising tool for characterizing the pathophysiology of cardiovascular diseases and provides significant prognostic information for cardiovascular risk assessment. Lower MPR has been associated with greater cardiovascular risk, as well as with markers of myocardial injury and more adverse left ventricular structural parameters (33). In this study, we similarly demonstrated that impaired myocardial perfusion is closely associated with higher ARR and greater left ventricular mass, suggesting that these factors may serve as early subclinical indicators of adverse structural remodeling.

Additionally, excess autonomous aldosterone secretion can cause damage to myocardial tissue, leading to myocardial fibrosis and scarring (37), independent of systemic blood pressure. Freel et al. found that patients with PA tend to have more severe myocardial fibrosis, manifesting as a diffuse, noninfarct pattern of late gadolinium enhancement on cardiac MRI in comparison with control study participants with EH (38). Late gadolinium enhancement is primarily used to identify focal myocardial fibrosis. However, late gadolinium enhancement requires a visual comparison between damaged and undamaged myocardium and may not be sensitive to aldosterone-induced, potentially reversible, diffuse myocardial fibrosis. T1 mapping techniques can detect changes in the characteristics of myocardial tissue, especially quantitative changes in diffuse myocardial fibrosis, with estimation of the ECV fraction (39). Zhou et al. reported that patients with PA had a higher ECV fraction than did patients with EH, with the degree of diffuse myocardial fibrosis potentially caused by high levels of plasma aldosterone concentration (40). In contrast, our cohort demonstrated no significant difference in baseline ECV fraction between patients with PA and those with EH. Posttreatment ECV values in patients with PA, however, were significantly higher compared with those in patients with EH. Nonetheless, we found that increased collagen deposition in myocardium and myocardial fibrosis may be reversed by surgery, which is consistent with a previous work (41).

Our study provides evidence that logARR is a strong predictor of left ventricular mass, MPR, and ECV. Our findings suggest that logARR can serve as a dynamic predictive tool for monitoring treatment response and guiding individualized management of PA. The decrease in logARR after treatment may serve as an early alternative endpoint for the reversal of cardiac remodeling. Although drug therapy significantly reduces blood pressure and normalizes serum potassium concentration, the low-dose titration may be insufficient for inducing significant cardiac alterations (42). If the decrease in logARR is not significant, early consideration should be given to increasing the dosage or reassessing the treatment strategy. Moreover, the frequency of follow-up imaging can be guided by the magnitude of ΔlogARR. Future multicenter studies are warranted to evaluate optimal ΔlogARR thresholds and to determine whether ARR-guided clinical decision-making leads to improved cardiovascular outcomes.

This study involved several limitations that should be addressed. To begin, this study exclusively included patients with PA who underwent surgical treatment and did not assess the reversibility of left ventricular remodeling in patients treated with MRAs. This omission limits external validity. Our conclusions may not fully extend to patients with PA managed with MRAs, and future comparative studies between surgical and medical therapy are needed. Additionally, the therapeutic responses were evaluated at a relatively short-term follow-up of 6 months, which might not have fully captured the long-term effects of treatment. Furthermore, as we employed a single-center design, the findings may be limited by the specific patient population and clinical practices at our institution. Therefore, multicenter, large-scale trials are needed to validate our results and to assess the generalizability of our findings. In addition, our assessment of myocardial fibrosis relied on ECV fraction alone, which is excellent for quantifying diffuse interstitial changes but may underestimate focal or patchy fibrosis. Finally, our study focused on structural remodeling and tissue characterization, but we did not employ advanced functional imaging techniques such as feature-tracking cardiac magnetic resonance or speckle-tracking echocardiography (43,44). These techniques could provide valuable complementary data on myocardial mechanics and subclinical systolic dysfunction, which may precede overt structural changes in hypertensive heart disease.

Conclusions

PA is associated with more severe cardiac remodeling and microvascular dysfunction as compared to EH, independent of age and sex. Targeted surgical intervention in patients with PA leads to significant resolution of microvascular dysfunction. An increase in logARR could be linked to left ventricular remodeling, cardiac dysfunction, and decreased MPR. Cardiac MRI is an effective method for evaluating treatment alterations in cardiac remodeling in both PA and patients with EH.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-401/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-401/dss

Funding: This research was supported by Hunan Provincial Health Commission (No. 202103062278) and Hunan Provincial Natural Science Foundation (No. 2022JJ30799).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-401/coif). R.C. reports that this study was supported by Hunan Provincial Health Commission (No. 202103062278) and Hunan Provincial Natural Science Foundation (No. 2022JJ30799). L.T. is an employee of Circle Cardiovascular Imaging Inc. H.G. is an employee of Siemens Healthineers Ltd. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics committee of the Second Xiangya Hospital of Central South University (No. 2010023815) and informed consent was obtained from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016;101:1889-916. [Crossref] [PubMed]
2. Funder JW, Carey RM. Primary Aldosteronism: Where Are We Now? Where to From Here? Hypertension 2022;79:726-35. [Crossref] [PubMed]
3. Inoue K, Goldwater D, Allison M, Seeman T, Kestenbaum BR, Watson KE. Serum Aldosterone Concentration, Blood Pressure, and Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis. Hypertension 2020;76:113-20. [Crossref] [PubMed]
4. Al-Hashedi EM, Abdu FA. Aldosterone Effect on Cardiac Structure and Function. Curr Cardiol Rev 2024;20:e290224227534. [Crossref] [PubMed]
5. Nguyen T, Do H, Pham T, Vu LT, Zuin M, Rigatelli G. Left ventricular dysfunction causing ischemia in patients with patent coronary arteries. Perfusion 2018;33:115-22. [Crossref] [PubMed]
6. Ohno Y, Sone M, Inagaki N, Kawashima A, Takeda Y, Yoneda T, et al. Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism. Hypertension 2020;75:1475-82. [Crossref] [PubMed]
7. Monticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2018;6:41-50. [Crossref] [PubMed]
8. Savard S, Amar L, Plouin PF, Steichen O. Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study. Hypertension 2013;62:331-6. [Crossref] [PubMed]
9. Yang Y, Zhu LM, Xu JZ, Tang XF, Gao PJ. Comparison of left ventricular structure and function in primary aldosteronism and essential hypertension by echocardiography. Hypertens Res 2017;40:243-50. [Crossref] [PubMed]
10. Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R, Sechi LA. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008;168:80-5. [Crossref] [PubMed]
11. Sethi R, Vishwakarma P, Pradhan A. Evidence for Aldosterone Antagonism in Heart Failure. Card Fail Rev 2024;10:e15. [Crossref] [PubMed]
12. Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P, Sechi LA. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 2007;50:911-8. [Crossref] [PubMed]
13. Rossi GP, Cesari M, Cuspidi C, Maiolino G, Cicala MV, Bisogni V, Mantero F, Pessina AC. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension 2013;62:62-9. [Crossref] [PubMed]
14. Lin YH, Lee HH, Liu KL, Lee JK, Shih SR, Chueh SC, Lin WC, Lin LC, Lin LY, Chung SD, Wu VC, Kuo CC, Ho YL, Chen MF, Wu KDTAIPAI Study Group. Reversal of myocardial fibrosis in patients with unilateral hyperaldosteronism receiving adrenalectomy. Surgery 2011;150:526-33. [Crossref] [PubMed]
15. Buffolo F, Tetti M, Mulatero P, Monticone S. Aldosterone as a Mediator of Cardiovascular Damage. Hypertension 2022;79:1899-911. [Crossref] [PubMed]
16. Hsu LY, Jacobs M, Benovoy M, Ta AD, Conn HM, Winkler S, Greve AM, Chen MY, Shanbhag SM, Bandettini WP, Arai AE. Diagnostic Performance of Fully Automated Pixel-Wise Quantitative Myocardial Perfusion Imaging by Cardiovascular Magnetic Resonance. JACC Cardiovasc Imaging 2018;11:697-707. [Crossref] [PubMed]
17. Tang L, Zhao W, Li K, Tian L, Zhou X, Guo H, Zeng M. Assessing microvascular dysfunction and predicting long-term prognosis in patients with cardiac amyloidosis by cardiovascular magnetic resonance quantitative stress perfusion. J Cardiovasc Magn Reson 2025;27:101134. [Crossref] [PubMed]
18. Kellman P, Wilson JR, Xue H, Ugander M, Arai AE. Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an automated method. J Cardiovasc Magn Reson 2012;14:63. [Crossref] [PubMed]
19. Kellman P, Hansen MS. T1-mapping in the heart: accuracy and precision. J Cardiovasc Magn Reson 2014;16:2. [Crossref] [PubMed]
20. Engblom H, Kanski M, Kopic S, Nordlund D, Xanthis CG, Jablonowski R, Heiberg E, Aletras AH, Carlsson M, Arheden H. Importance of standardizing timing of hematocrit measurement when using cardiovascular magnetic resonance to calculate myocardial extracellular volume (ECV) based on pre- and post-contrast T1 mapping. J Cardiovasc Magn Reson 2018;20:46. [Crossref] [PubMed]
21. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MSAmerican Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539-42. [Crossref] [PubMed]
22. Kotecha T, Martinez-Naharro A, Boldrini M, Knight D, Hawkins P, Kalra S, Patel D, Coghlan G, Moon J, Plein S, Lockie T, Rakhit R, Patel N, Xue H, Kellman P, Fontana M. Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology. JACC Cardiovasc Imaging 2019;12:1958-69. [Crossref] [PubMed]
23. Wang M. Generalized Estimating Equations in Longitudinal Data Analysis: A Review and Recent Developments. Advances in Statistics 2014;2014:303728.
24. Cuspidi C, Tadic M, Sala C, Quarti-Trevano F, Gherbesi E, Mancia G, Grassi G. Regression of left ventricular hypertrophy in primary aldosteronism after adrenalectomy: a meta-analysis of echocardiographic studies. J Hypertens 2021;39:775-83. [Crossref] [PubMed]
25. Wu T, Ren Y, Wang W, Cheng W, Zhou F, He S, Liu X, Li L, Tang L, Deng Q, Zhou X, Chen Y, Sun J. Left Ventricular Remodeling in Patients with Primary Aldosteronism: A Prospective Cardiac Magnetic Resonance Imaging Study. Korean J Radiol 2021;22:1619-27. [Crossref] [PubMed]
26. Grytaas MA, Sellevåg K, Thordarson HB, Husebye ES, Løvås K, Larsen TH. Cardiac magnetic resonance imaging of myocardial mass and fibrosis in primary aldosteronism. Endocr Connect 2018;7:413-24. [Crossref] [PubMed]
27. Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, Gabetti L, Mengozzi G, Williams TA, Rabbia F, Veglio F, Mulatero P. Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice. J Am Coll Cardiol 2017;69:1811-20. [Crossref] [PubMed]
28. Redheuil A, Blanchard A, Pereira H, Raissouni Z, Lorthioir A, Soulat G, Vargas-Poussou R, Amar L, Paul JL, Helley D, Azizi M, Kachenoura N, Mousseaux E. Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance. JACC Cardiovasc Imaging 2020;13:2149-59. [Crossref] [PubMed]
29. Hundemer GL, Agharazii M, Madore F, Vaidya A, Brown JM, Leung AA, Kline GA, Larose E, Piché ME, Crean AM, Shaw JLV, Ramsay T, Hametner B, Wassertheurer S, Sood MM, Hiremath S, Ruzicka M, Goupil R. Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study. Circulation 2024;149:124-34. [Crossref] [PubMed]
30. Chang YC, Wu XM, Chen TY, Chen UL, Liao CW, Lai TS, Chang CC, Lee BC, Yang FY, Chen ZW, Chang YY, Chueh JS, Wu VC, Tsai CH, Hung CS, Lin YHTAIPAI study group. Evaluating the effects of adrenalectomy and mineralocorticoid receptor antagonist on cardiac remodeling and diastolic function in patients with aldosterone-producing adenoma. Hypertens Res 2025;48:529-39. [Crossref] [PubMed]
31. Patil S, Rojulpote C, Amanullah A. Primary Aldosteronism and Ischemic Heart Disease. Front Cardiovasc Med 2022;9:882330. [Crossref] [PubMed]
32. Ohno Y, Sone M, Inagaki N, Yamasaki T, Ogawa O, Takeda Y, et al. Prevalence of Cardiovascular Disease and Its Risk Factors in Primary Aldosteronism: A Multicenter Study in Japan. Hypertension 2018;71:530-7. [Crossref] [PubMed]
33. Xu X, Divakaran S, Weber BN, Hainer J, Laychak SS, Auer B, Kijewski MF, Blankstein R, Dorbala S, Trinquart L, Slomka PJ, Zhang L, Brown JM, Di Carli MF. Relationship of Subendocardial Perfusion to Myocardial Injury, Cardiac Structure, and Clinical Outcomes Among Patients With Hypertension. Circulation 2024;150:1075-86. [Crossref] [PubMed]
34. Napoli C, Di Gregorio F, Leccese M, Abete P, Ambrosio G, Giusti R, Casini A, Ferrara N, De Matteis C, Sibilio G, Donzelli R, Montemarano A, Mazzeo C, Rengo F, Mansi L, Liguori A. Evidence of exercise-induced myocardial ischemia in patients with primary aldosteronism: the Cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study. J Investig Med 1999;47:212-21.
35. Zorach B, Shaw PW, Bourque J, Kuruvilla S, Balfour PC Jr, Yang Y, Mathew R, Pan J, Gonzalez JA, Taylor AM, Meyer CH, Epstein FH, Kramer CM, Salerno M. Quantitative cardiovascular magnetic resonance perfusion imaging identifies reduced flow reserve in microvascular coronary artery disease. J Cardiovasc Magn Reson 2018;20:14. [Crossref] [PubMed]
36. Rahman H, Scannell CM, Demir OM, Ryan M, McConkey H, Ellis H, Masci PG, Perera D, Chiribiri A. High-Resolution Cardiac Magnetic Resonance Imaging Techniques for the Identification of Coronary Microvascular Dysfunction. JACC Cardiovasc Imaging 2021;14:978-86. [Crossref] [PubMed]
37. Brilla CG, Weber KT. Reactive and reparative myocardial fibrosis in arterial hypertension in the rat. Cardiovasc Res 1992;26:671-7. [Crossref] [PubMed]
38. Freel EM, Mark PB, Weir RA, McQuarrie EP, Allan K, Dargie HJ, McClure JD, Jardine AG, Davies E, Connell JM. Demonstration of blood pressure-independent noninfarct myocardial fibrosis in primary aldosteronism: a cardiac magnetic resonance imaging study. Circ Cardiovasc Imaging 2012;5:740-7. [Crossref] [PubMed]
39. Taylor AJ, Salerno M, Dharmakumar R, Jerosch-Herold M. T1 Mapping: Basic Techniques and Clinical Applications. JACC Cardiovasc Imaging 2016;9:67-81. [Crossref] [PubMed]
40. Zhou F, Wu T, Wang W, Cheng W, Wan S, Tian H, Chen T, Sun J, Ren Y. CMR-Verified Myocardial Fibrosis Is Associated With Subclinical Diastolic Dysfunction in Primary Aldosteronism Patients. Front Endocrinol (Lausanne) 2021;12:672557. [Crossref] [PubMed]
41. Lin YH, Wu XM, Lee HH, Lee JK, Liu YC, Chang HW, Lin CY, Wu VC, Chueh SC, Lin LC, Lo MT, Ho YL, Wu KDTAIPAI Study Group. Adrenalectomy reverses myocardial fibrosis in patients with primary aldosteronism. J Hypertens 2012;30:1606-13. [Crossref] [PubMed]
42. Chen YL, Xu TY, Xu JZ, Zhu LM, Li Y, Wang JG. A Prospective Comparative Study on Cardiac Alterations After Surgery and Drug Treatment of Primary Aldosteronism. Front Endocrinol (Lausanne) 2021;12:770711. [Crossref] [PubMed]
43. Liu H, Wang J, Pan Y, Ge Y, Guo Z, Zhao S. Early and Quantitative Assessment of Myocardial Deformation in Essential Hypertension Patients by Using Cardiovascular Magnetic Resonance Feature Tracking. Sci Rep 2020;10:3582. [Crossref] [PubMed]
44. Sonaglioni A, Lonati C, Lombardo M, Rigamonti E, Binda G, Vincenti A, Nicolosi GL, Bianchi S, Harari S, Anzà C. Incremental prognostic value of global left atrial peak strain in women with new-onset gestational hypertension. J Hypertens 2019;37:1668-75. [Crossref] [PubMed]