Effect of the geometry and severity of left ventricular hypertrophy on cardiovascular mortality in dialysis patients.

Background: Left ventricular hypertrophy (LVH) is a vital risk factor for mortality of dialysis patients. The association of the geometry and severity of LVH with cardiovascular and all-cause mortality in hemodialysis (HD) patients remains unknown. This study investigated clinical outcomes among HD patients with different LVH geometric patterns and severity. Methods: The monocentric retrospective cohort study enrolled chronic HD patients who underwent echocardiography for the assessment of LVH. The patients with LVH were divided into concentric and eccentric groups and then subdivided into four groups based on LVH severity: mild-to-moderate eccentric, mild-to-moderate concentric, severe eccentric, and severe concentric LVH. The risks of cardiovascular and all-cause mortality between groups were evaluated using Cox proportional hazard analysis. Results: Of the 237 patients on HD with LVH, 131 had concentric LVH, and 106 had eccentric LVH, with 33, 44, 73, and 87 having mild-to-moderate eccentric, mild-to-moderate concentric, severe eccentric, and severe concentric LVH, respectively. Compared with eccentric LVH, the crude hazard ratio (cHR) of cardiovascular mortality of concentric LVH was 2.03 (95% confidence interval [CI], 1.13-3.65). Severe concentric LVH was a significant risk factor for all-cause and cardiovascular mortality compared with mild-to-moderate eccentric LVH (cHR: 2.58 [95% CI, 1.00-6.65] and 3.73 [95% CI, 1.13-12.33], respectively). After adjustment for all variables, concentric LVH and severe concentric LVH remained significant risk factors for cardiovascular mortality (adjusted HR: 2.13 [95% CI, 1.13-4.01] and 3.71 [95% CI, 1.07-12.82], respectively). Conclusion: Concentric LVH, especially severe concentric LVH, was associated with a high risk of cardiovascular mortality among patients with chronic HD.

Involvement of pentraxin-3 in the development of hypertension but not left ventricular hypertrophy in male spontaneously hypertensive rats.

Hypertension drives the development of concentric left ventricular hypertrophy (LVH). However, the relative contribution of pentraxin-3 (PTX-3), a novel marker for inflammatory cardiovascular disease, in the hypertrophic response to pressure overload has not been adequately elucidated. We investigated the role of PTX-3 in the development of LVH in spontaneously hypertensive rats (SHR), untreated and treated with either captopril (an ACE inhibitor) or hydralazine (a non-specific vasodilator). Three-month-old SHR received either 20 mg/kg/day hydralazine (SHR + H, n = 6), 40 mg/kg/day captopril (SHR + C, n = 6), or plain gelatine cubes (untreated SHR, n = 7) orally for 4 months. Wistar Kyoto rats (WKY, n = 7) were used as the normotensive controls. Blood pressure (BP) was measured using the tail-cuff method. Cardiac geometry and function were determined using M-mode echocardiography. Circulating concentrations of inflammatory markers were measured in plasma by ELISA. LV fibrosis and cardiomyocyte width were assessed by histology. Relative mRNA expression of PTX-3 was determined in the LV by RT-PCR. Untreated SHR exhibited greater systolic BP and relative wall thickness (RWT) compared to WKY. Captopril and hydralazine normalized BP but only captopril reversed RWT in SHR. Circulating PTX-3 and VCAM-1 levels were elevated in untreated SHR and reduced with captopril and hydralazine. Circulating PTX-3 was positively associated with systolic BP but lacked independent relations with indices of LVH. LV relative mRNA expression of PTX-3 was similar between the groups. PTX-3 may not be involved in the development of LVH in SHR, but plausibly reflects the localized inflammatory milieu associated with hypertension.

The impact of ventricular remodeling on quality-of-life outcomes after Transcatheter aortic valve replacement.

BACKGROUND: Among patients with aortic stenosis, ventricular remodeling by hypertrophy can limit the augmentation of flow with exertion, even after valve intervention. However, the effect of hypertrophy on quality of life (QoL) improvement has not been studied. We aimed to determine the effect of ventricular hypertrophy on QoL outcomes after transcatheter aortic valve replacement (TAVR). METHODS: All patients undergoing TAVR from 2011 to 2021 at our institution were included. Groups were divided into none/mild ventricular hypertrophy (non-remodeled, NR) and moderate/severe left ventricular hypertrophy (VH) according to guideline-recommended cut-offs for left ventricular (LV) wall thickness. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was utilized to assess QoL; primary outcome was KCCQ change <5 from baseline to 30 days and 1 year. RESULTS: We analyzed 679 patients (NR: N = 389, VH: N = 290). Groups differed by septal thickness (1.12 cm vs. 1.44 cm, p < 0.001), posterior wall thickness (1.08 cm vs. 1.33 cm, p < 0.001), and LV internal diastolic diameter (4.34 cm vs. 4.19 cm, p = 0.006). The primary outcome was similar between NR and VH at 30 days (31.6 % vs. 28.6 %, p = 0.449) and 1 year (27.7 % vs. 21.5 %, p = 0.217). NR and VH experienced similar proportions of worsening, no change, or small, moderate, and large improvements in KCCQ score. Both groups experienced similar domain score changes and New York Heart Association class improvement. A subgroup analysis of VH patients did not reveal interaction with cavity size or stroke volume. CONCLUSION: Patients with significant ventricular remodeling by hypertrophy and aortic stenosis have similar QoL changes after intervention compared to patients without significant remodeling.

Distinguishing hypertensive cardiomyopathy from cardiac amyloidosis in hypertensive patients with heart failure: a CMR study with histological confirmation.

PURPOSE: Differentiation of the cause of left ventricular hypertrophy (LVH) is challenging in cases with co-existing hypertension. CMR offers assessment of diffuse myocardial abnormalities via T1 mapping with extracellular volume fraction (ECV) and macroscopic fibrosis via late gadolinium enhancement imaging (LGE). The goal of the study was to understand if CMR parameters can differentiate hypertensive cardiomyopathy (HC) from cardiac amyloidosis (CA) in patients with hypertension and heart failure, using endomyocardial biopsy (EMB) as the gold standard. METHODS: We retrospectively analyzed patients with hypertension, LVH, and heart failure undergoing EMB due to uncertain diagnosis. CMR parameters including cine, LGE characteristics, T1 mapping, and ECV were analyzed. RESULTS: A total of 34 patients were included (mean age 66.5 ± 10.7 years, 79.4% male). The final EMB-based diagnosis was HC (10, 29%), light chain (AL) CA (7, 21%), and transthyretin (ATTR) CA (17, 50%). There was a significant difference in subendocardial LGE (p = 0.03) and number of AHA segments with subendocardial LGE (p = 0.005). The subendocardial LGE pattern was most common in AL-CA (85.7%) and African American with HC (80%). ECV elevation (≥ 29%) was present in all patients with CA (AL-CA: 57.6 ± 5.2%, ATTR-CA: 59.1 ± 15.3%) and HC (37.3 ± 4.5%). CONCLUSIONS: Extensive subendocardial LGE pattern is not pathognomonic for CA but might also be present in African American patients with longstanding or poorly controlled HTN. The ECV elevation in HC with HF might be more significant than previously reported with an overlap of ECV values in HC and CA, particularly in younger African American patients.

Nocturnal blood pressure dipping and left ventricular hypertrophy among hypertensive outpatients in a Ghanaian hospital.

Objectives: To investigate the association between the extent of nocturnal systolic blood pressure decline and left ventricular hypertrophy in patients with primary hypertension who were receiving antihypertensive drug therapy. Design: This was a cross-sectional hospital-based study from November 2020 to March 2021. Setting: The study was conducted at the Polyclinic of Korle Bu Teaching Hospital, Ghana. Participants: Outpatients ≥18 years old with primary hypertension who were receiving antihypertensive drug therapy. Interventions: Each participant underwent a 24-hour ambulatory blood pressure monitoring and a transthoracic echocardiogram. Main outcome measures: Left ventricular hypertrophy and the extent of mean systolic blood pressure decline during sleep. Results: 180 participants were recruited, comprising 110 (61.1%) females. The participants' mean (±SD) age was 57.6 ± 11.0 years. 80% had a non-dipping blood pressure pattern, and 43.9% had left ventricular hypertrophy. Uncontrolled office blood pressure was an independent predictor of left ventricular hypertrophy in these patients (AOR 2.010, 95% CI 1.048-3.855, p=0.036); however, a non-dipping nocturnal systolic blood pressure status was not (AOR 1.849, 95% CI 0.850-4.022, p=0.121). 61.1% had abnormal left ventricular geometry, with concentric hypertrophy being the predominant geometric pattern. Conclusion: Left ventricular hypertrophy and non-dipping nocturnal blood pressure were common in these hypertensive Ghanaian patients on antihypertensive therapy. Left ventricular hypertrophy was associated with uncontrolled office blood pressure but not the extent of nocturnal systolic blood pressure declines during a single 24-hour ambulatory blood pressure recording. Funding: None declared.

Alternative Factors in Possible Involvement of Coronary Microvascular Dysfunction in Older Patients with HFpEF.

Objectives: Coronary microvascular dysfunction (CMD) is associated with many heart diseases, including heart failure (HF) with preserved ejection fraction (HFpEF). Invasive examinations for CMD detection are difficult in older patients with HFpEF, and the decision criteria for noninvasive CMD measurements are unclear. We aimed to identify alternative factors in the possible involvement of CMD in the progression and prognosis of HFpEF. Methods: We analyzed 607 patients with HFpEF who were hospitalized for acute decompensated HF without a history of coronary artery disease (CAD). Blood tests and transthoracic echocardiography were performed. We focused on left ventricular hypertrophy (LVH) and coronary perfusion pressure (diastolic blood pressure, dBP). Results: The patients with LVH showed reduced diastolic function (E/e') and a lower incidence of atrial fibrillation (AF) compared with those without LVH, with no differences in age or dBP. No differences were observed in all-cause mortality between patients with low and high dBP without LVH. In the patients with LVH, the incidence of all-cause mortality was significantly higher, with a lower incidence of AF, reduced renal function, and higher C-reactive protein levels in those with low dBP than in those with high dBP. The comprehensive diastolic functional index, diastolic elastance/arterial elastance, was markedly higher in the patients with LVH, especially in those with all-cause mortality. This index, but not E/e', was a significant prognostic index in the multivariate Cox hazard analysis when adjusting for age, sex and N-terminal pro-brain natriuretic peptide levels. Conclusions: LVH and dBP were clinically important factors in elderly HFpEF patients without a history of CAD.

Proteomic biomarkers and pathway analysis for progression to heart failure in three epidemiological representative cohorts.

AIMS: Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population-based cohorts. METHODS AND RESULTS: A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow-up of 13 (11-14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case-control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28-1.71]; DD OR 1.71 [1.53-1.92]; HF HR 1.98 [1.66-2.36]); STANISLAS (LVH OR 1.20 [1.02-1.41]; DD OR 1.46 [1.12-1.90]); HOMAGE (HF HR 1.85 [1.62-2.12]). Galectin-4, growth differentiation factor 15 and suppression of tumorigenicity-2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF. CONCLUSION: In conclusion, our study reinforces the role of NT-proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT-proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets.

Concept, study design, and baseline nighttime blood pressure control status of the WISDOM-Night Study using a wrist-type oscillometric home blood pressure monitoring device.

There is growing evidence that nocturnal hypertension is an independent risk factor for cardiovascular diseases, including heart failure. However, brachial blood pressure (BP) measurements during sleep might themselves disturb sleep quality. We initiated a nationwide, multicenter observational prospective study using a wrist-type oscillometric nighttime BP monitoring device with new algorithms to measure supine BP accurately without sleep disturbance. This study, named the Wrist ICT-based Sleep and Circadian Blood Pressure Monitoring Program-Night BP Study (WISDOM-Night Study), was designed to clarify the impact of wrist-measured daily nighttime BPs on cardiovascular prognosis (stroke, coronary artery disease, heart failure, etc.) using 7 days of BP measurements at 2:00 a.m., 3:00 a.m., 4:00 a.m., and 4 h after bedtime. A total of 2751 patients with one or more cardiovascular risk factors were recruited between March 2021 and March 2024 and are currently being followed up for 7 years. Additionally, 1416 of the WISDOM-Night Study-enrolled patients who also agreed to participate in the WISDOM-Hypertension-Mediated Organ Damage (HMOD) Study underwent echocardiography to evaluate the association between wrist-measured BP and left ventricular structure. Data from this WISDOM-Night Study should provide the prospective association between nighttime BP and cardiovascular disease and reveal the indexes of nighttime BP with clinical pathological relevance. This first report of the WISDOM-Night Study describes the study design, baseline characteristics, and BP control status.

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0-2.

BACKGROUND: The clinical significance of echocardiographic left ventricular hypertrophy (LVH) in risk stratification of left atrial appendage (LAA) thrombogenic milieu, as a surrogate for cardioembolic risk, in patients with atrial fibrillation (AF) and HA2DS2-VASc scores of 0-2 is unknown. METHODS AND RESULTS: We enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0-2 who underwent transesophageal echocardiography. LAA thrombogenic milieu was defined as the presence of a thrombus, severe spontaneous echo contrast, sludge in the LAA, or LAA flow velocity ≤ 20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium were obtained using transthoracic echocardiography. Among the 707 patients, 77 (10.9 %) exhibited LVH. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH group (32.5 % vs. 2.5 %, p < 0.001). LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and left atrium volume index) (odds ratio [OR]: 7.54, 95 % confidence interval [CI]: 3.49-16.29, p < 0.001 and OR: 7.16, 95 % CI: 3.26-15.73, p < 0.001, respectively). Moreover, LVH provided incremental value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and left atrium reservoir strains (p < 0.001). CONCLUSION: Echocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0-2.

Characterizing myocardial edema and fibrosis in hypertensive crisis with cardiovascular magnetic resonance imaging.

A hypertensive crisis is associated with an increased risk of cardiovascular events. Although altered cardiac structure, function, and myocardial architecture on cardiovascular magnetic resonance (CMR) have been associated with increased adverse events in hypertensive patients, the studies did not include patients with hypertensive crisis. Our study aimed to determine myocardial tissue characteristics in patients with hypertensive crisis using CMR imaging. Participants underwent comprehensive CMR imaging at 1.5T. The imaging protocol included cine-, T2-weighted-, contrasted- and multi-parametric mapping images. Blood and imaging biomarkers were compared in hypertensive emergency and hypertensive urgency. Predictors of myocardial edema was assessed using linear regression. The predictive value of T1- and T2 mapping for identifying hypertensive emergency (from urgency) was assessed with receiver operator characteristics curves. Eighty-two patients (48.5 ± 13.4 years, 57% men) were included. Hypertensive emergency constituted 78%. Native T1 was higher in patients with LVH compared to those without (1056 ± 33 vs. 1013 ± 40, P < 0.001), and tended to be higher in hypertensive emergency than urgency (1051 ± 37 vs. 1033 ± 40, P = 0.077). T2-w signal intensity (SI) ratio and T2 mapping values were higher in hypertensive emergency (1.5 ± 0.2 vs. 1.4 ± 0.1, P = 0.044 and 48 ± 2 vs. 47 ± 2, P = 0.004), and in patients with than without LVH (1.5 ± 0.2 vs. 1.4 ± 0.1, P = 0.045 and P = 0.030). A trend for higher extracellular volume was noted in hypertensive emergency compared to urgency (25 ± 4 vs. 22 ± 3, P = 0.050). Native T1 correlated with T2 mapping (rs = 0.429, P < 0.001), indexed LV mass (rs = 0.493, P < 0.001), cardiac troponin (rs = 0.316, P < 0.001) and NT-proBNP (rs = 0.537, P < 0.001), while T2 correlated with cardiac troponin (rs = 0.390, P < 0.001), and NT-proBNP (rs = 0.348, P < 0.001). Non-ischemic LGE pattern occurred in 59% and was 21% more prevalent in the hypertensive emergency group (P = 0.005). Our findings demonstrate that hypertensive crisis is associated with distinct myocardial tissue alterations, including increased myocardial edema and fibrosis, as detected on CMR. Patients with hypertensive emergency had a higher degree of myocardial oedema than hypertensive urgency. Further research is necessary to explore the prognostic value of these findings.

Carotid intima-media thickness, fibroblast growth factor 23, and mineral bone disorder in children with chronic kidney disease.

BACKGROUND: Carotid intima-media thickness (cIMT) is a measure of atherosclerotic vascular disease and a surrogate biomarker for cardiovascular risk in patients with chronic kidney disease (CKD). Mineral and bone disorders (MBD) are complications of CKD, contributing to vascular calcification and accelerated atherosclerosis. Increased fibroblast growth factor 23 (FGF23)-the earliest detectable serum abnormality associated with CKD-MBD-has been linked with cardiovascular disease in patients with CKD. This study aimed to identify factors and analyze the relationship associated with high cIMT, high FGF23, and poor MBD control in children with CKD. METHODS: A cross-sectional study was conducted in Yogyakarta, Indonesia recruiting children with CKD. The correlations and factors between cIMT, FGF23, and MBD were explored. RESULTS: We recruited 42 children aged 2-18 years old with CKD stages 2 to 5D. There were no significant correlations between cIMT and factors including advanced CKD, use of dialysis, body mass index, hypertension, anemia, MBD, FGF23 levels, and left ventricular mass index (LVMI). Patients with advanced CKD had poorly controlled anemia, hypertension, and higher LVMI. In multivariate analysis, CKD stages, hypertension stages, the presence of MBD, and LVMI were associated with FGF23 levels (p < 0.05). CONCLUSIONS: FGF23 levels increased with CKD progression, and MBD was more prevalent in advanced kidney disease. Elevated FGF23 is potentially associated with increased MBD prevalence in late-stage CKD. A larger study is needed to confirm the factors affecting cIMT in children with CKD.

Cardiometabolic risk in children and adolescents with obesity: a position paper of the Italian Society for Pediatric Endocrinology and Diabetology.

Despite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age.The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB.This Position paper, released by experts of the "Childhood Obesity study group" within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence.The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality.

Fine Tuning ECG Interpretation for Young Athletes: ECG Screening Using Z-score-based Analysis.

BACKGROUND: Electrocardiograms (ECGs) in athletes commonly reveal findings related to physiologic adaptations to exercise, that may be difficult to discern from true underlying cardiovascular abnormalities. North American and European societies have published consensus statements for normal, borderline, and abnormal ECG findings for athletes, but these criteria are not based on established correlation with disease states. Additionally, data comparing ECG findings in athletes to non-athlete control subjects are lacking. Our objective was to compare the ECGs of collegiate athletes and non-athlete controls using Z-scores for digital ECG variables to better identify significant differences between the groups and to evaluate the ECG variables in athletes falling outside the normal range. METHODS: Values for 102 digital ECG variables on 7206 subjects aged 17-22 years, including 672 athletes, from Hawaii Pacific Health, University of Hawaii, and Rady Children's Hospital San Diego were obtained through retrospective review. Age and sex-specific Z-scores for ECG variables were derived from normal subjects and used to assess the range of values for specific ECG variables in young athletes. Athletes with abnormal ECGs were referred to cardiology consultation and/or echocardiogram. RESULTS: Athletes had slower heart rate, longer PR interval, more rightward QRS axis, longer QRS duration but shorter QTc duration, larger amplitude and area of T waves, prevalent R' waves in V1, and higher values of variables traditionally associated with left ventricular hypertrophy (LVH): amplitudes of S waves (leads V1-V2), Q waves (V6, III) and R waves (II, V5, V6). Z-scores of these ECG variables in 558 (83%) of the athletes fell within - 2.5 and 2.5 range derived from the normal population dataset, and 60 (8.9%) athletes had a Z-score outside the - 3 to 3 range. While 191 (28.4%) athletes met traditional voltage criteria for diagnosis of LVH on ECG, only 53 athletes (7.9%) had Z-scores outside the range of -2.5 to 2.5 for both S amplitude in leads V1-V2 and R amplitude in leads V5-6. Only one athlete was diagnosed with hypertrophic cardiomyopathy with a Z-score of R wave in V6 of 2.34 and T wave in V6 of -5.94. CONCLUSION: The use of Z-scores derived from a normal population may provide more precise screening to define cardiac abnormalities in young athletes and reduce unnecessary secondary testing, restrictions and concern.

Effects of hemodynamic load on cardiac remodeling in fish and mammals: the value of comparative models.

The ability of the vertebrate heart to remodel enables the cardiac phenotype to be responsive to changes in physiological conditions and aerobic demand. Examples include exercise-induced cardiac hypertrophy, and the significant remodeling of the trout heart during thermal acclimation. Such changes are thought to occur in response to a change in hemodynamic load (i.e. the forces that the heart must work against to circulate blood). Variations in hemodynamic load are caused by either a volume overload (high volume of blood returning to the heart, impairing contraction) or a pressure overload (elevated afterload pressure that the heart must contract against). The changes observed in the heart during remodeling are regulated by multiple cellular signaling pathways. The cardiac response to these regulatory mechanisms occurs across levels of biological organization, affecting cardiac morphology, tissue composition and contractile function. Importantly, prolonged exposure to pressure overload can cause a physiological response - that improves function - to transition to a pathological response that causes loss of function. This Review explores the role of changes in hemodynamic load in regulating the remodeling response, and considers the cellular signals responsible for regulating remodeling, incorporating knowledge gained from studying biomedical models and comparative animal models. We specifically focus on the renin-angiotensin system, and the role of nitric oxide, oxygen free radicals and transforming growth factor beta. Through this approach, we highlight the strong conservation of the regulatory pathways of cardiac remodeling, and the specific conditions within endotherms that may be conducive to the development of pathological phenotypes.

Finerenone and left ventricular hypertrophy in chronic kidney disease and type 2 diabetes.

AIMS: Left ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co-morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double-blind, placebo-controlled, multicentre FIDELIO-DKD and FIGARO-DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline. METHODS AND RESULTS: A diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator-reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) ≥57% from baseline over ≥4 weeks, or kidney-related death. Safety outcomes by baseline LVH were reported as treatment-emergent adverse events. At baseline out of 13 026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator-reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (Pinteraction = 0.1075 for composite CV outcome and Pinteraction = 0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (Pinteraction = 0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment-emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups. CONCLUSIONS: In conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF.

When Paying Attention Pays Back: Missense Mutation c.1006G>A p. (Val336Ile) in PRKAG2 Gene Causing Left Ventricular Hypertrophy and Conduction Abnormalities in a Caucasian Patient: Case Report and Literature Review.

PRKAG2 cardiomyopathy is a rare genetic disorder that manifests early in life with an autosomal dominant inheritance pattern. It harbors left ventricular hypertrophy (LVH), ventricular pre-excitation and progressively worsening conduction system defects. Its estimated prevalence among patients with LVH ranges from 0.23 to about 1%, but it is likely an underdiagnosed condition. We report the association of the PRKAG2 missense variant c.1006G>A p. (Val336Ile) with LVH, conduction abnormalities (short PR interval and incomplete right bundle branch bock) and early-onset arterial hypertension (AH) in a 44-year-old Caucasian patient. While cardiac magnetic resonance (CMR) showed a mild hypertrophic phenotype with maximal wall thickness of 17 mm in absence of tissue alterations, the electric phenotype was relevant including brady-tachy syndrome and recurrent syncope. The same variant has been detected in the patient's sister and daughter, with LVH + early-onset AH and electrocardiographic (ECG) alterations + lipothymic episodes, respectively. Paying close attention to the coexistence of LVH and ECG alterations in the proband has been helpful in directing genetic tests to exclude primary cardiomyopathy. Hence, identifying the genetic basis in the patient allowed for familial screening as well as a proper follow-up and therapeutic management of the affected members. A review of the PRKAG2 cardiomyopathy literature is provided alongside the case report.

Predictive value of remnant cholesterol for left ventricular hypertrophy and prognosis in hypertensive patients with heart failure: a prospective study.

BACKGROUND AND AIM: Remnant cholesterol (RC) is substantially related to negative outcomes in cardiac patients. Patients with coexisting hypertension and heart failure (HF) often develop left ventricular hypertrophy (LVH) and have poor prognoses. This study investigated baseline RC levels and LV remodelling and patients' prognoses. METHODS AND RESULTS: Six hundred thirty consecutive individuals with hypertension and HF participated in this prospective trial from October 2018 to August 2020. Based on left ventricular mass index (LVMI), 560 those eligible were separated into LVH and non-LVH groups. Multiple linear regression and receiver operating characteristic (ROC) curves examined the RC and LV relationship. A Cox regression analysis was conducted to examine the predictive value of RC for clinical outcomes. The LVH group presented significantly elevated values of RC, triglyceride, and cholesterol and decreased high-density lipoprotein cholesterol (HDLC). The optimal cutoff value for RC to predict LV remodelling was 0.49. The subjects were observed for a median of 58 months, and 104 participants met the primary endpoint. The risk models involving the two Cox models were adjusted to incorporate confounding factors, which revealed that those with elevated baseline levels of RC were more susceptible to cardiovascular mortality, as shown by an increased hazard ratio. (HR: 1.91, 95% CI: 1.62-2.26 vs. HR: 1.75, 95% CI: 1.43-2.16, P < 0.001). CONCLUSIONS: RC is linked to LV remodelling in patients with hypertensive HF, with LVH having greater RC values. Moreover, patients with hypertensive HF who had a higher RC suffered from an increased risk of cardiovascular mortality. TRIAL REGISTRATION: NCT03727828, 21 Oct 2018.

A Cautionary Tale of Hypertrophic Cardiomyopathy-From "Benign" Left Ventricular Hypertrophy to Stroke, Atrial Fibrillation, and Molecular Genetic Diagnostics: A Case Report and Review of Literature.

This case report concerns a 48-year-old man with a history of ischemic stroke at the age of 41 who reported cardiac hypertrophy, registered in his twenties when explained by increased physical activity. Family history was positive for a mother with permanent atrial fibrillation from her mid-thirties. At the age of 44, he had a first episode of persistent atrial fibrillation, accompanied by left atrial thrombosis while on a direct oral anticoagulant. He presented at our clinic at the age of 45 with another episode of persistent atrial fibrillation and decompensated heart failure. Echocardiography revealed a dilated left atrium, reduced left ventricular ejection fraction, and an asymmetric left ventricular hypertrophy. Cardiac magnetic resonance was positive for a cardiomyopathy with diffuse fibrosis, while slow-flow phenomenon was present on coronary angiography. Genetic testing by whole-exome sequencing revealed three variants in the patient, c.309C > A, p.His103Gln in the ACTC1 gene, c.116T > G, p.Leu39Ter in the PLN gene, and c.5827C > T, p.His1943Tyr in the SCN5A gene, the first two associated with hypertrophic cardiomyopathy and the latter possibly with familial atrial fibrillation. This case illustrates the need for advanced diagnostics in unexplained left ventricular hypertrophy, as hypertrophic cardiomyopathy is often overlooked, leading to potentially debilitating health consequences.