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Circulation Jan 2024Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for (myosin light chain 3) to ≈55% for (myosin-binding protein C3), ≈60% for (troponin T2) and (troponin I3), and ≈65% for (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for and ≈23% for .
CONCLUSIONS
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Topics: Humans; Adult; Penetrance; Mutation; Cross-Sectional Studies; Pedigree; Cardiomyopathy, Hypertrophic; Troponin T
PubMed: 37929589
DOI: 10.1161/CIRCULATIONAHA.123.065987 -
Transplantation Direct Jun 2024Left ventricular hypertrophy (LVH) in patients with end stage renal disease undergoing renal replacement is linked to an increased risk for cardiovascular diseases....
BACKGROUND
Left ventricular hypertrophy (LVH) in patients with end stage renal disease undergoing renal replacement is linked to an increased risk for cardiovascular diseases. Dialysis does not completely prevent or correct this abnormality, and the evidence for kidney transplantation (KT) varies. This analysis aims to explore the relationship between KT and LVH.
METHODS
MEDLINE and Scopus were systematically searched in October 2023. All cross-sectional and longitudinal studies that fulfilled our inclusion criteria were included. Outcome was left ventricular mass index (LVMI) changes. We conducted a meta-analysis using a random effects model. Meta-regression was applied to examine the LVMI changes dependent on various covariates. Sensitivity analysis was used to handle outlying or influential studies and address publication bias.
RESULTS
From 7416 records, 46 studies met the inclusion criteria with 4122 included participants in total. Longitudinal studies demonstrated an improvement of LVMI after KT -0.44 g/m (-0.60 to -0.28). Blood pressure was identified as a predictor of LVMI change. A younger age at the time of KT and well-controlled anemia were also associated with regression of LVH. In studies longitudinally comparing patients on dialysis and renal transplant recipients, no difference was detected -0.09 g/m (-0.33 to 0.16). Meta-regression using changes of systolic blood pressure as a covariate showed an association between higher blood pressure and an increase in LVMI, regardless of the modality of renal replacement treatment.
CONCLUSIONS
In conclusion, our results indicated a potential cardiovascular benefit, defined as the regression of LVH, after KT. This benefit was primarily attributed to improved blood pressure control rather than the transplantation itself.
PubMed: 38769973
DOI: 10.1097/TXD.0000000000001647 -
Journal of Science and Medicine in Sport Sep 2021A hypertensive response to exercise (HRE) is associated with cardiovascular disease and high blood pressure (BP). Sub-clinical changes to cardiac structure may underlie... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
A hypertensive response to exercise (HRE) is associated with cardiovascular disease and high blood pressure (BP). Sub-clinical changes to cardiac structure may underlie these associations, although this has not been systematically determined. Via systematic review and meta-analysis, we aimed to (1) assess the relationship between exercise BP and cardiac structure, and (2) determine if cardiac structure is altered in those with an HRE, across various study populations (including those with/without high BP at rest).
DESIGN AND METHODS
Three online databases were searched for cross-sectional studies reporting exercise BP, HRE and cardiac structural variables. Random-effects meta-analyses and meta-regressions were used to calculate pooled correlations between exercise BP and cardiac structure, and pooled mean differences and relative risk between those with/without an HRE.
RESULTS
Forty-nine studies, (n=23,707 total; aged 44±4 years; 63% male) were included. Exercise systolic BP was associated with increased left ventricular (LV) mass, LV mass index, relative wall thickness, posterior wall thickness and interventricular septal thickness (p<0.05 all). Those with an HRE had higher risk of LV hypertrophy (relative risk: 2.6 [1.85-3.70]), increased LV mass (47±7g), LV mass index (7±2g/m), relative wall thickness (0.02±0.005), posterior wall thickness (0.78±0.20mm), interventricular septal thickness (0.78±0.17mm) and left atrial diameter (2±0.52mm) vs. those without an HRE (p<0.05 all). Results were broadly similar between studies with different population characteristics.
CONCLUSIONS
Exercise systolic BP is associated with cardiac structure, and those with an HRE show evidence towards adverse remodelling. Results were similar across different study populations, highlighting the hypertension-related cardiovascular risk associated with an HRE.
Topics: Adult; Aged; Blood Pressure; Cardiovascular Diseases; Cross-Sectional Studies; Exercise; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Hypertrophy, Right Ventricular; Male; Middle Aged; Regression Analysis; Risk; Systole; Ventricular Remodeling; Ventricular Septum; Young Adult
PubMed: 33707155
DOI: 10.1016/j.jsams.2021.02.014 -
Open Heart Jul 2023Fabry disease (FD) is an X-linked lysosomal storage disorder caused by enzyme deficiency, leading to glycosphingolipid accumulation. Cardiac accumulation triggers local...
INTRODUCTION
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by enzyme deficiency, leading to glycosphingolipid accumulation. Cardiac accumulation triggers local tissue injury, electrical instability and arrhythmia. Bradyarrhythmia and atrial fibrillation (AF) incidence are reported in up to 16% and 13%, respectively.
OBJECTIVE
We conducted a systematic review evaluating AF burden and bradycardia requiring permanent pacemaker (PPM) implantation and report any predictive risk factors identified.
METHODS
We conducted a literature search on studies in adults with FD published from inception to July 2019. Study outcomes included AF or bradycardia requiring therapy. Databases included Embase, Medline, PubMed, Web of Science, CINAHL and Cochrane. The Risk of Bias Agreement tool for Non-Randomised Studies (RoBANS) was utilised to assess bias across key areas.
RESULTS
11 studies were included, eight providing data on AF incidence or PPM implantation. Weighted estimate of event rates for AF were 12.2% and 10% for PPM. Age was associated with AF (OR 1.05-1.20 per 1-year increase in age) and a risk factor for PPM implantation (composite OR 1.03). Left ventricular hypertrophy (LVH) was associated with AF and PPM implantation.
CONCLUSION
Evidence supporting AF and bradycardia requiring pacemaker implantation is limited to single-centre studies. Incidence is variable and choice of diagnostic modality plays a role in detection rate. Predictors for AF (age, LVH and atrial dilatation) and PPM (age, LVH and PR/QRS interval) were identified but strength of association was low. Incidence of AF and PPM implantation in FD are variably reported with arrhythmia burden likely much higher than previously thought.
PROSPERO DATABASE
CRD42019132045.
Topics: Adult; Humans; Bradycardia; Atrial Fibrillation; Fabry Disease; Incidence; Pacemaker, Artificial
PubMed: 37460269
DOI: 10.1136/openhrt-2023-002316 -
The Cochrane Database of Systematic... Oct 2021Hypertension is the leading preventable risk factor for cardiovascular disease and premature death worldwide. One of the clinical effects of hypertension is left... (Review)
Review
BACKGROUND
Hypertension is the leading preventable risk factor for cardiovascular disease and premature death worldwide. One of the clinical effects of hypertension is left ventricular hypertrophy (LVH), a process of cardiac remodelling. It is estimated that over 30% of people with hypertension also suffer from LVH, although the prevalence rates vary according to the LVH diagnostic criteria. Severity of LVH is associated with a higher prevalence of cardiovascular disease and an increased risk of death. The role of antihypertensives in the regression of left ventricular mass has been extensively studied. However, uncertainty exists regarding the role of antihypertensive therapy compared to placebo in the morbidity and mortality of individuals with hypertension-induced LVH.
OBJECTIVES
To assess the effect of antihypertensive pharmacotherapy compared to placebo or no treatment on morbidity and mortality of adults with hypertension-induced LVH.
SEARCH METHODS
Cochrane Hypertension's Information Specialist searched the following databases for studies: Cochrane Hypertension Specialised Register (to 26 September 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; 2020, Issue 9), Ovid MEDLINE (1946 to 22 September 2020), and Ovid Embase (1974 to 22 September 2020). We searched the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov for ongoing trials. We also searched Epistemonikos (to 19 February 2021), LILACS BIREME (to 19 February 2021), and Clarivate Web of Science (to 26 February 2021), and contacted authors and funders of the identified trials to obtain additional information and individual participant data. There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with at least 12 months' follow-up comparing antihypertensive pharmacological therapy (monotherapy or in combination) with placebo or no treatment in adults (18 years of age or older) with hypertension-induced LVH were eligible for inclusion. The trials must have analysed at least one primary outcome (all-cause mortality, cardiovascular events, or total serious adverse events) to be considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors screened the search results, with any disagreements resolved by consensus amongst all review authors. Two review authors carried out the data extraction and analyses. We assessed risk of bias of the included studies following Cochrane methodology. We used the GRADE approach to assess the certainty of the body of evidence.
MAIN RESULTS
We included three multicentre RCTs. We selected 930 participants from the included studies for the analyses, with a mean follow-up of 3.8 years (range 3.5 to 4.3 years). All of the included trials performed an intention-to-treat analysis. We obtained evidence for the review by identifying the population of interest from the trials' total samples. None of the trials provided information on the cause of LVH. The intervention varied amongst the included trials: hydrochlorothiazide plus triamterene with the possibility of adding alpha methyldopa, spironolactone, or olmesartan. Placebo was administered to participants in the control arm in two trials, whereas participants in the control arm of the remaining trial did not receive any add-on treatment. The evidence is very uncertain regarding the effect of additional antihypertensive pharmacological therapy compared to placebo or no treatment on mortality (14.3% intervention versus 13.6% control; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.74 to 1.40; 3 studies; 930 participants; very low-certainty evidence); cardiovascular events (12.6% intervention versus 11.5% control; RR 1.09, 95% CI 0.77 to 1.55; 3 studies; 930 participants; very low-certainty evidence); and hospitalisation for heart failure (10.7% intervention versus 12.5% control; RR 0.82, 95% CI 0.57 to 1.17; 2 studies; 915 participants; very low-certainty evidence). Although both arms yielded similar results for total serious adverse events (48.9% intervention versus 48.1% control; RR 1.02, 95% CI 0.89 to 1.16; 3 studies; 930 participants; very low-certainty evidence) and total adverse events (68.3% intervention versus 67.2% control; RR 1.07, 95% CI 0.86 to 1.34; 2 studies; 915 participants), the incidence of withdrawal due to adverse events may be significantly higher with antihypertensive drug therapy (15.2% intervention versus 4.9% control; RR 3.09, 95% CI 1.69 to 5.66; 1 study; 522 participants; very low-certainty evidence). Sensitivity analyses limited to blinded trials, trials with low risk of bias in core domains, and trials with no funding from the pharmaceutical industry did not change the results of the main analyses. Limited evidence on the change in left ventricular mass index prevented us from drawing any firm conclusions.
AUTHORS' CONCLUSIONS
We are uncertain about the effects of adding additional antihypertensive drug therapy on the morbidity and mortality of participants with LVH and hypertension compared to placebo. Although the incidence of serious adverse events was similar between study arms, additional antihypertensive therapy may be associated with more withdrawals due to adverse events. Limited and low-certainty evidence requires that caution be used when interpreting the findings. High-quality clinical trials addressing the effect of antihypertensives on clinically relevant variables and carried out specifically in individuals with hypertension-induced LVH are warranted.
Topics: Adolescent; Adult; Antihypertensive Agents; Cardiovascular Diseases; Humans; Hypertension; Hypertrophy, Left Ventricular; Methyldopa
PubMed: 34628642
DOI: 10.1002/14651858.CD012039.pub3 -
Herz Dec 2020Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular mortality and morbidity. Several studies have reported that it affects the left ventricle;... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular mortality and morbidity. Several studies have reported that it affects the left ventricle; however, large randomized controlled trials are lacking. The current study aimed to summarize the association between OSAS and left ventricular (LV) structure and function.
METHODS
Electronic databases (PubMed, Embase, and Cochrane) and references were searched for articles published until March 2018. A systematic review and meta-analysis were performed to assess LV structure and function in OSAS patients based on echocardiography.
RESULTS
In total, 17 studies with 747 OSAS patients and 426 control participants were included. Patients with OSAS showed an increase in LV diastolic diameter (weighted mean difference [WMD], 95% CI: 1.24 [0.68, 1.80]; p < 0.001), LV systolic diameter (WMD, 95% CI: 1.14 [0.47, 1.81]; p = 0.001), and LV mass (WMD, 95% CI: 35.34 [20.67, 50.00]; p < 0.001). In addition, left ventricular ejection fraction (LVEF) significantly decreased in the OSAS group compared with the controls (WMD, 95% CIs: -1.82 [-2.76, -0.87]; p < 0.001), and the reduction in LVEF was consistent with the severity of OSAS. The OSAS group also showed an increase in left atrial diameter (WMD, 95% CI: 2.13 [1.48, 2.77]; p < 0.001) and left atrial diameter volume index (WMD, 95% CIs: 3.96 [3.32, 4.61]; p < 0.001).
CONCLUSION
Obstructive sleep apnea syndrome leads to atrial dilatation, left ventricular hypertrophy, enlargement, mass increase and reduction of systolic function. Treatments for OSAS might be beneficial for the preservation of left cardiac structure and function.
Topics: Echocardiography; Humans; Sleep Apnea, Obstructive; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling
PubMed: 31555891
DOI: 10.1007/s00059-019-04850-w -
Clinical Hypertension Sep 2023In patients with end-stage renal disease (ESRD) undergoing dialysis, hypertension is common but often inadequately controlled. The prevalence of hypertension varies... (Review)
Review
In patients with end-stage renal disease (ESRD) undergoing dialysis, hypertension is common but often inadequately controlled. The prevalence of hypertension varies widely among studies because of differences in the definition of hypertension and the methods of used to measure blood pressure (BP), i.e., peri-dialysis or ambulatory BP monitoring (ABPM). Recently, ABPM has become the gold standard for diagnosing hypertension in dialysis patients. Home BP monitoring can also be a good alternative to ABPM, emphasizing BP measurement outside the hemodialysis (HD) unit. One thing for sure is pre- and post-dialysis BP measurements should not be used alone to diagnose and manage hypertension in dialysis patients. The exact target of BP and the relationship between BP and all-cause mortality or cause-specific mortality are unclear in this population. Many observational studies with HD cohorts have almost universally reported a U-shaped or even an L-shaped association between BP and all-cause mortality, but most of these data are based on the BP measured in HD units. Some data with ABPM have shown a linear association between BP and mortality even in HD patients, similar to the general population. Supporting this, the results of meta-analysis have shown a clear benefit of BP reduction in HD patients. Therefore, further research is needed to determine the optimal target BP in the dialysis population, and for now, an individualized approach is appropriate, with particular emphasis on avoiding excessively low BP. Maintaining euvolemia is of paramount importance for BP control in dialysis patients. Patient heterogeneity and the lack of comparative evidence preclude the recommendation of one class of medication over another for all patients. Recently, however, β-blockers could be considered as a first-line therapy in dialysis patients, as they can reduce sympathetic overactivity and left ventricular hypertrophy, which contribute to the high incidence of arrhythmias and sudden cardiac death. Several studies with mineralocorticoid receptor antagonists have also reported promising results in reducing mortality in dialysis patients. However, safety issues such as hyperkalemia or hypotension should be further evaluated before their use.
PubMed: 37653470
DOI: 10.1186/s40885-023-00240-x -
Frontiers in Endocrinology 2022This systematic review and meta-analysis was performed to compare the effect of sodium-glucose cotransporter protein-2 inhibitors (SGLT-2i) and placebo on left... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review and meta-analysis was performed to compare the effect of sodium-glucose cotransporter protein-2 inhibitors (SGLT-2i) and placebo on left ventricular hypertrophy (LVH) in patients with type 2 diabetes.
METHOD
Randomized controlled trials (RCTs) comparing the LVH parameters of SGLT-2i to placebo in patients with type 2 diabetes were included. Our primary outcomes were the changes in left ventricular mass (LVM) and left ventricular mass index (LVMI) from baseline to the study endpoint. Secondary outcomes were the changes in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early mitral inflow velocity to atrial inflow velocity (E/A). Summary odds ratios were estimated using a fixed-effect or random-effect model.
RESULTS
A total of 11 articles were included. Data were extracted from 11 original studies matching our inclusion criteria. In our meta-analysis, there were significant improvement in LVM (SMD -0.23, 95% CI -0.44 to -0.02, = 22.6%, = 0.034), LVMI (SMD -0.25, 95% CI -0.38 to -0.12, = 0.0%, = 0.000), LVEDV (SMD -0.19, 95% CI -0.36 to -0.01, = 62.3%, = 0.035), and LVESV (SMD -0.21, 95% CI -0.39 to -0.04, = 32.9%, = 0.017) in the SGLT-2i group compared with the placebo group. Furthermore, no significant differences were found in LVEF (SMD 0.13, 95% CI 0.00 to 0.26, = 0.0%, = 0.050) and E/A (SMD -0.01, 95% CI -0.22 to 0.20, = 0%, = 0.908) between the two groups.
CONCLUSIONS
This meta-analysis confirmed the beneficial effects of SGLT-2i on reversal of left ventricular remodeling. The LVH regression was more pronounced in studies of type 2 diabetes patients receiving SGLT-2i than placebo.
Topics: Humans; Hypertrophy, Left Ventricular; Diabetes Mellitus, Type 2; Ventricular Function, Left; Glucose; Sodium
PubMed: 36699027
DOI: 10.3389/fendo.2022.1088820 -
Frontiers in Cardiovascular Medicine 2022Left ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP...
BACKGROUND
Left ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP with primary hypertension (PH).
METHODS
A meta-analysis of prevalence was performed. A literature search of articles reporting LVH in CYP with PH was conducted in Medline, Embase, and Cochrane databases. Studies with a primary focus on CYP (up to 21 years) with PH were included. Meta-regression was used to analyze factors explaining observed heterogeneity.
RESULTS
The search yielded a total of 2,200 articles, 153 of those underwent full-text review, and 47 reports were included. The reports evaluated 51 study cohorts including 5,622 individuals, 73% male subjects, and a mean age of 13.6 years. LVH was defined as left ventricle mass index (LVMI) ≥ 95th percentile in 22 (47%), fixed cut-off ≥38.6 g/m in eight (17%), sex-specific fixed cut-off values in six (13%), and miscellaneously in others. The overall prevalence of LVH was 30.5% (95% CI 27.2-33.9), while heterogeneity was high ( = 84%). Subgroup analysis including 1,393 individuals (76% male subjects, mean age 14.7 years) from pediatric hypertension specialty clinics and LVH defined as LVMI ≥95th percentile only (19 study cohorts from 18 studies), reported prevalence of LVH at 29.9% (95% CI 23.9 to 36.3), and high heterogeneity ( = 84%). Two studies involving patients identified through community screening ( = 1,234) reported lower LVH prevalence (21.5%). In the meta-regression, only body mass index (BMI) z-score was significantly associated with LVH prevalence (estimate 0.23, 95% CI 0.08-0.39, = 0.004) and accounted for 41% of observed heterogeneity, but not age, male percentage, BMI, or waist circumference z-score. The predominant LVH phenotype was eccentric LVH in patients from specialty clinics (prevalence of 22% in seven studies with 779 participants) and one community screening study reported the predominance of concentric LVH (12%).
CONCLUSION
Left ventricular hypertrophy is evident in at least one-fifth of children and young adults with PH and in nearly a third of those referred to specialty clinics with a predominant eccentric LVH pattern in the latter. Increased BMI is the most significant risk association for LVH in hypertensive youth.
PubMed: 36386367
DOI: 10.3389/fcvm.2022.993513 -
Pharmacology Research & Perspectives Apr 2024Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease,... (Review)
Review
Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis. Ultimately, this can progress to the development of heart failure, arrhythmias, and cardiogenic shock, with severe cases even resulting in sudden cardiac death. Despite several decades of both fundamental and clinical research conducted globally, there are currently no specific targeted therapies available for DCM in clinical practice, and the incidence and mortality rates of heart failure remain persistently high. Thus, this article provides an overview of the current treatment modalities and novel techniques pertaining to DCM, aiming to offer valuable insights and support to researchers dedicated to investigating this complex condition.
Topics: Humans; Diabetic Cardiomyopathies; Heart Failure; Coronary Artery Disease; Myocardial Infarction; Cardiovascular Agents; Diabetes Mellitus
PubMed: 38407563
DOI: 10.1002/prp2.1177