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Objective: Noninvasive measurement of myocardial work (MW) incorporates left ventricular (LV) pressure, and, therefore, allows correction of global longitudinal strain for changing afterload conditions. We sought to investigate MW as a tool to detect early signs of LV dysfunction in primary systemic hypertension patients, particularly with different predictive indices., Methods and Results: None left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) patients established were all primary systemic hypertension with preserved ejection fraction. Forty in NLVH and forty in LVH according to left ventricular end-diastolic mass index (LVEDmassI) were prospectively enrolled. The following indices of MW were assessed: global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE). Both global work index ( P =0.348) and global constructive work ( P =0.225) were increased in NLVH and decreased in LVH, and GWW ( P <0.001) was increased significantly in NLVH and increased more in LVH, while GWE ( P <0.001) was decreased significantly in NLVH and decreased more in LVH. The clinical utility of GWW (95% CI: 0.802-0.951) and GWE (95% CI: 0.811-0.950) were verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with LVH and control comparisons. In multivariate linear regression analysis, 4-dimenaional LVEDmassI was independently associated with GWE ( P =0.018) in systemic hypertension patients. Assessment of intraobserver and interobserver variability in the MW echocardiographic data documented good interclass correlation coefficients (all >0.85)., Conclusion: GWW and GWE derived from MW are more accurate, sensitive, and reproducible predictors to detect early LV dysfunction in primary systemic hypertension patients, especially in distinguishing the potential functional abnormality of NLVH and LVH, even though the ejection fraction is preserved., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized., Methods: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension., Results: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P <0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP., Conclusions: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension., Competing Interests: Disclosures Dr Vaidya reports consulting fees from Mineralys, Corcept, and HRA Pharma, outside of the submitted work. Dr Brown reports consulting fees from Bayer and AstraZeneca, outside of the submitted work. Dr Sood reports speaker fees from AstraZeneca, Otsuka, Bayer, and GlaxoSmithKline, outside of the submitted work.

Background and Objectives: Reports assessing the association of stroke risk factors with incident stroke have generally assumed a uniform magnitude of associations across the age spectrum, an assumption we assess in this report., Methods: Participants enrolled 2003-2007 in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study who were stroke free at baseline were followed for incident stroke. Associations of traditional stroke risk factors with incident stroke were assessed using (1) proportional hazards analysis based on the baseline age of the participant and (2) Poisson regression analysis assessing associations based on the changing age of the participant during their follow-up (age at exposure). In each analysis, age strata were selected to have a similar number of strokes in each stratum, specifically 45-64, 65-73, and 74+ years for the proportional hazards analysis and 45-69, 70-79, and 80+ years for Poisson regression., Results: A total of 1,405 ischemic stroke events occurred among 28,235 participants over a median follow-up of 11.3 years, with a total of 276,074 person-years exposure. For both analytic approaches, the magnitude of the association with stroke was significantly less at older ages for diabetes (hazard or relative risk decreasing from ≈2.0 in younger strata to ≈1.3 in older strata), heart disease (from ≈2.0 to ≈1.3), and hypertension defined at a threshold of 140/90 mm Hg (from ≈1.80 to ≈1.50); however, there was no age-related difference in the magnitude of the association for smoking, atrial fibrillation, or left ventricular hypertrophy., Discussion: Hypertension and diabetes are 2 of the more important risk factors for stroke; however, their association with stroke risk appears substantially less at older ages. That the magnitude of the association for smoking, atrial fibrillation, and left ventricular hypertrophy does not decrease with age suggests their relative importance in determining stroke risk likely increases with age., (© 2023 American Academy of Neurology.)

The frontal QRS-T angle (fQRS-T angle) in ECG is a new measure of myocardial repolarization, in which a higher fQRS-T angle is linked with worse cardiac outcomes. Reverse dipper hypertension is also linked to poor cardiac outcomes. The purpose of this study was to investigate the association between the fQRS-T angle and reverse dipper status in individuals newly diagnosed with hypertension who did not have left ventricular hypertrophy (LVH). The investigation recruited 171 hypertensive individuals without LVH who underwent 24-h ambulatory blood pressure monitoring (ABPM). On the basis of the findings of 24-h ABPM, the study population was categorized into the following three groups: patients with dipper hypertension, non-dipper hypertension, and reverse dipper hypertension. LVH was defined by echocardiography. The fQRS-T angle was measured using the 12-lead ECG. The fQRS-T angle in individuals with reverse dipper hypertension was substantially greater than in patients with and without dipper hypertension (51° ± 28° vs. 28° ± 22° vs. 39° ± 25°, respectively, P < 0.001). The fQRS-T angle (odds ratio: 1.040, 95% confidence interval: 1.016-1.066; P = 0.001) was independently associated with reverse dipper hypertension according to multivariate analysis. In receiver operating characteristic curve analysis, the fQRS-T angle to predict reverse dipper hypertension was 33.5° with 76% sensitivity and 71% specificity. This study showed that an increased fQRS-T angle was associated with reverse dipper hypertension in newly diagnosed hypertensive patients without LVH., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Noncommunicable diseases including cardiovascular diseases are becoming an important part of human immunodeficiency virus (HIV) care. Echocardiography is a useful noninvasive tool to assess cardiac disease and different echocardiographic abnormalities have been seen previously. The aim of this study was to investigate the echocardiographic abnormalities in HIV-infected patients and factors associated with the findings. A cross-sectional study was conducted on 285 patients with HIV infection including collection of clinical and echocardiographic data. Logistic regression was used to examine the association between echocardiographic abnormalities and associated factors with variables with a P value of <.05 in the multivariate model considered statistically significant. Diastolic dysfunction was the most common abnormality seen in 30% of the participants followed by ischemic heart disease (19.3%), left ventricular hypertrophy (10.2%), enlarged left atrium (8.1%), pulmonary hypertension (3.6%), and pericardial effusion (2.1%). Diastolic dysfunction was independently associated with increasing age, elevated blood pressure, and left ventricular hypertrophy while ischemic heart disease was associated with male gender, increasing age, and abnormal fasting blood glucose. Left ventricular hypertrophy was associated with increasing age and blood pressure and the later was associated with left atrial enlargement. The level of immunosuppression did not affect echocardiography findings. A high prevalence of echocardiographic abnormalities was found. Male gender, age >50 years, elevated blood pressure, and elevated fasting blood glucose were associated with echocardiographic abnormalities. Appropriate follow-up and treatment of echocardiographic abnormalities is needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort., Methods: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids)., Results: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk., Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Objectives: Left ventricular (LV) hypertrophy in resistant hypertensive patients is associated with a reduced intramyocardial perfusion. Renal sympathetic denervation (RDN) has been shown to reduce blood pressure (BP) and sympathetic tone. We aimed to prospectively investigate the effect of RDN on functional myocardial parameters and myocardial perfusion reserve (MPR) using cardiac magnetic resonance imaging (cMRI) in patients with resistant hypertension., Methods: A total of 15 resistant hypertensive patients (11 male individuals, mean age 62±13 y) were included. Adenosine stress-induced cMRI was performed at baseline, 3, 6, and 12 months after RDN. RDN was performed using a single soft-tip radiofrequency catheter (Symplicity). cMRI semiquantitative perfusion analysis was performed using the upslope of myocardial signal enhancement to derive the myocardial perfusion reserve index., Results: Both systolic-BP and diastolic-BP significantly decreased from 148±14 to 133±14 mm Hg and 87±14 to 80±10 mm Hg, respectively (P<0.05). LV septal wall thickness was significantly reduced (P<0.001). LV ejection fraction and MPR lacked significant trends 12 months after RDN., Conclusions: In this pilot study, RDN significantly reduced LV mass and LV septal wall thickness, as diagnosed by cMRI, with no significant changes in MPR. cMRI may help in diagnosing clinically relevant changes of functional myocardial parameters after interventional therapy in resistant hypertensive patients.

Objective: The objective of this study was to investigate the characteristics of 24-hour ambulatory blood pressure monitoring and its relationship with cardiovascular target organ damage (left ventricular hypertrophy and carotid atherosclerosis) in Chinese Han patients with concomitant type 2 diabetes mellitus and hypertension., Methods: A total of 830 hypertensive patients with or without type 2 diabetes mellitus were divided into four groups according to blood pressure patterns. Clinical characteristics and 24-hour ambulatory blood pressure monitoring indexes were compared among the four groups. Multivariable logistic regression was used to identify the associations among clinical characteristics, blood pressure variability and cardiovascular target organ damage., Results: The prevalence of the non-dipper blood pressure profile (51.32% vs. 24.33%) was higher in patients with type 2 diabetes mellitus and hypertension than in those without type 2 diabetes mellitus. Logistic regression analysis showed that glycosylated haemoglobin A1c, 24hSBP, 24hSSD, dSBP, nSBP and nSSD were independently associated with the non-dipper blood pressure pattern. Type 2 diabetes mellitus patients with the non-dipper blood pressure pattern showed a higher occurrence of target organ damage compared to patients in the other three groups. Multivariate regression analyses revealed that duration of hypertension, fasting blood glucose, dDBP and nDSD were associated with left ventricular hypertrophy. Age, haemoglobin A1c, LDL-C, nSBP and HDL-C were independently related to carotid atherosclerosis., Conclusion: In the Chinese Han population, patients with concomitant type 2 diabetes mellitus and hypertension showed a remarkably high prevalence of non-dipper blood pressure patterns. Abnormal systolic blood pressure level and hyperglycemia were significantly associated with a non-dipper blood pressure pattern. Non-dipper blood pressure pattern, hyperglycemia and dyslipidemia were closely related to left ventricular hypertrophy and carotid atherosclerosis.

Recent studies have shown that hypertension is poorly controlled in many populations worldwide. Electrocardiographic left ventricular hypertrophy is a common manifestation of preclinical cardiovascular disease that strongly predicts cardiovascular disease morbidity and mortality. However, little information is available regarding the role of left ventricular hypertrophy in blood pressure (BP) control. We aimed to assess the relationship between electrocardiographic left ventricular hypertrophy and BP control in the China Stroke Primary Prevention Trial. The study population included 17,312 hypertensive patients who were selected from a group of 20,702 adults who had participated in the China Stroke Primary Prevention Trial and had undergone electrocardiography at baseline visit. Multivariate analysis identified left ventricular hypertrophy as a predictor of unsatisfactory BP control. The results revealed that 8.1% of hypertensive adults exhibit left ventricular hypertrophy and that the disease is more prevalent in males (12.8%) than in females. Multivariate regression analysis showed that the electrocardiographic left ventricular hypertrophy group had a significantly higher rate of unsatisfactory BP control [odds ratio (OR) 1.42, 95% confidence interval (95% CI) 1.26-1.61, P < .001) than the nonleft ventricular hypertrophy group.Notable differences in BP control were also observed among males (OR 1.37, 95% CI 1.17-1.60, P < .001) and females (OR 1.45, 95% CI 1.18-1.77, P < .001) and especially among patients with comorbid diabetes (OR 2.32, 95% CI 1.31-4.12, P = .004). In conclusion, the results of this study indicate that electrocardiographic left ventricular hypertrophy appears to be an independent predictive factor for poor BP control, especially in females and patients with comorbid diabetes.

Background: Few studies have assessed the role of 24-h ambulatory blood pressure monitoring (ABPM) in adults with nondialysis chronic kidney disease (CKD). We examined the potential determinants of left ventricular hypertrophy (LVH) and mass index (LVMI) in this population., Participants and Methods: We carried out a cross-sectional study on 69 stage 3b-5 CKD adults who had ABPM and transthoracic echocardiography performed simultaneously. Hypertension (HT) was defined as 24 h blood pressure (BP) of at least 130/80 mmHg. ABPM parameters considered were BP dipping status, BP load, and the BP night-time/daytime ratio. We performed stepwise backward multivariate linear and logistic regression to assess the determinants of LVH and LVMI. ABPM parameters were considered the main independent variables, whereas HT, angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist use, glomerular filtration rate of less than 30 ml/min/1.72 m, diabetes, smoking, age, sex, hemoglobin, and parathyroid hormone levels were considered covariates., Results: LVH was present in 22 (31.8%) patients. In linear regression analysis, systolic [β=-13.8, 95% confidence interval (CI)=-26.3 to -1.3, P=0.031] and mean (β=-13.5, 95% CI=-25.7 to -1.2, P=0.031) nondipping status was associated with increased LVMI. BP load and night-time/daytime ABPM ratio were not associated with LVMI. In logistic regression analysis, systolic nondipping status (odds ratio=0.27, 95% CI=0.08-0.91, P=0.036) was associated with LVH. Among covariates, estimated glomerular filtration rate of less than 30 ml/min/1.72 m and HT were associated with LVH and increased LVMI. At 1-year follow-up, mean nondipping status on the initial ABPM remained associated significantly with increased LVMI (β=-19.8, 95% CI=-36.6 to -3.0, P=0.022)., Conclusion: These data confirm the high incidence of LVH among nonrenal replacement therapy CKD patients and suggest that the nondipping phenomenon on ABPM is associated independently with LVH and increased LVMI in this population.

Objective: We determined differences in the prevalence of blood pressure (BP) phenotypes and the association of these phenotypes with left ventricular hypertrophy (LVH) for individuals who fulfilled and did not fulfill various criteria used for defining a complete ambulatory blood pressure monitoring (ABPM) recording., Methods: We analyzed data for 1141 participants from the Jackson Heart Study. Criteria evaluated included having greater than or equal to 80% of planned readings with more than or equal to one reading per hour (Spanish ABPM Registry criteria), more than or equal to 70% of planned readings with a minimum of 20 daytime and seven nighttime readings (2013 European Society of Hypertension criteria), greater than or equal to 14 daytime and greater than or equal to seven nighttime readings (2003 European Society of Hypertension criteria), more than or equal to 10 daytime and more than or equal to 5 nighttime readings (International Database of Ambulatory Blood Pressure in Relation to Cardiovascular Outcome criteria), and greater than or equal to 14 daytime readings (UK National Institute of Health and Clinical Excellence criteria)., Results: Between 45.0% (Spanish ABPM Registry) and 91.8% (UK National Institute of Health and Clinical Excellence) of the participants fulfilled the different criteria for a complete ABPM recording. Across the various criteria evaluated, 55.5-57.8% of participants had nocturnal hypertension and 62.8-66.8% had nondipping systolic BP. Among participants with clinic-measured systolic/diastolic BP of more than or equal to 140/90 mmHg, 22.9-26.5% had white-coat hypertension. The prevalence of daytime, 24-h, sustained, and masked hypertension differed by up to 2% for participants fulfilling each criterion. The association of BP phenotypes with LVH was similar for participants who fulfilled versus those who did not fulfill different criteria (each P>0.05)., Conclusion: Irrespective of the criteria used for defining a complete ABPM recording, the prevalence of BP phenotypes and their association with LVH were similar.

Left ventricular hypertrophy (LVH) is highly prevalent in kidney transplant recipients and is associated with poor clinical outcome. Immunosuppressive agents might affect LVH behavior after kidney transplantation. This review is an appraisal of available data regarding LVH in renal transplantation and especially of studies that evaluated LVH response to treatment. In particular, the role of mammalian target of rapamycin inhibitors adopted as immunosuppressive agents in kidney transplantation is reviewed in the light of recent studies that have shown LVH regression induced by this class of medications in kidney transplant recipients with posttransplant cardiomyopathy. Larger randomized controlled trials are warranted to confirm these findings and to ascertain the impact of such LVH regression on hard endpoints in kidney transplant recipients with posttransplant cardiomyopathy.

Left atrial enlargement (LAE) is a risk factor for cardiovascular complications and death. In hypertensive patients, LAE is usually due to left ventricular (LV) hypertrophy and diastolic dysfunction. We aimed to identify factors associated with LAE in patients with increased and normal left ventricular mass index (LVMI) with reference to pulsatile and steady components of blood pressure (BP).The study was carried out as a cross-sectional observation. In a group of inhabitants of suburban area of Cracow, Poland, we measured office, ambulatory and central BP, carotid-femoral pulse wave velocity (PWV), as well as echocardiographic indices and gathered anthropometric data, information on habits and relevant medical history. Further, with division according to sex-stratified dichotomised LVMI, we performed correlation analysis to identify possibly significant relations between measures of left atrial volume and other studied parameters. We also fitted regression models in order to assess the respective value of steady and pulsatile BP components as factors related to measures of left atrial volume.The mean age of 205 patients (136 females-66%) was 53.6 ± 8.3 years. We found higher values of PWV, office, ambulatory and central BPs in the group of LVMI above median value. This group had also greater left atrial volume index (LAVI), which correlated with LVMI (r = 0.36, P < .001) and ratio of early diastolic mitral peak flow velocity to early diastolic mitral annulus mean velocity in tissue Doppler imaging (E/e') (r = 0.24, P = .04).In the group of LVMI below the median, LAVI correlated with pulsatile and steady BP components. LAVI was independently predicted by mean arterial pressure (MAP) obtained from both ambulatory (MAP24h, β= 0.15; P = .045) and office measurements (MAPoffice, β = 0.35; P = .004), but not by pulse pressure.LV mass and function are the main determinants of LAVI. However, in persons with lower LV mass, LAVI depends on the steady component of blood pressure, but not pulsatile one. Increased LAVI reflects early changes in response to systemic blood pressure elevation., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Left ventricular hypertrophy (LVH) is common in endogenous hypertension (EH). We evaluated annexin A5 (ANXA5) promoter polymorphism in a cross-sectional study with a total of 850 EH patients, including 337 EH patients with LVH.Genotyping of ANXA5 promoter single nucleotide polymorphisms (SNPs) was conducted by SNaPshot assays and statistical analyses were performed to quantify its association with LVH.Of all potential SNPs, rs1050606 showed significant association with LVH (P = .008 in dominant and P = .006 in codominant models, respectively). During further analysis of SNPs on ANXA5 promoter region, rs1050606 had the most prominent effect. Furthermore, haplotypes M2 had higher risk of inducing LVH in EH patients compared with M1 (P = .032, OR = 1.42, 95%CI = 1.03-1.94). Patients with ANXA5 promoter haplotype GATGTC were also more susceptible to LVH (P = .022, OR = 1.35, 95%CI = 1.04-1.74). In the luciferase experiment, ANXA5 rs1050606 had the most promoter activity in myocardial cells (P < .001).These results showed that ANXA5 rs1050606 was significantly associated with LVH in Chinese EH patients, likely via influencing ANXA5 expression in serum and in myocardial cells.

Background: In the conventional paradigm of the progression of left ventricular hypertrophy, a thick-walled left ventricle (LV) ultimately transitions to a dilated cardiomyopathy. There are scant data in humans demonstrating whether this transition occurs commonly without an interval myocardial infarction., Methods and Results: Participants (n=1282) from the Dallas Heart Study underwent serial cardiac magnetic resonance ≈7 years apart. Those with interval cardiovascular events and a dilated LV (increased LV end-diastolic volume [EDV] indexed to body surface area) at baseline were excluded. Multivariable linear regression models tested the association of concentric hypertrophy (increased LV mass and LV mass/volume 0.67 ) with change in LVEDV. The study cohort had a median age of 44 years, 57% women, 43% black, and 11% (n=142) baseline concentric hypertrophy. The change in LVEDV in those with versus without concentric hypertrophy was 1 mL (-9 to 12) versus -2 mL (-11 to 7), respectively, P <0.01. In multivariable linear regression models, concentric hypertrophy was associated with larger follow-up LVEDV ( P ≤0.01). The progression to a dilated LV was uncommon (2%, n=25)., Conclusions: In the absence of interval myocardial infarction, concentric hypertrophy was associated with a small, but significantly greater, increase in LVEDV after 7-year follow-up. However, the degree of LV enlargement was minimal, and few participants developed a dilated LV. These data suggest that if concentric hypertrophy does progress to a dilated cardiomyopathy, such a transition would occur over a much longer timeframe (eg, decades) and perhaps less common than previously thought., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00344903., (© 2017 American Heart Association, Inc.)

Background: It is currently unknown whether intensive blood pressure (BP) lowering beyond that recommended would lead to more lowering of the risk of left ventricular hypertrophy (LVH) in patients with hypertension and whether reducing the risk of LVH explains the reported cardiovascular disease (CVD) benefits of intensive BP lowering in this population., Methods: This analysis included 8164 participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP <120 mm Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm Hg). Progression and regression of LVH as defined by Cornell voltage criteria derived from standard 12-lead ECGs recorded at baseline and biannually were compared between treatment arms during a median follow-up of 3.81 years. The effect of intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and CVD death) was compared before and after adjustment for LVH as a time-varying covariate., Results: Among SPRINT participants without baseline LVH (n=7559), intensive (versus standard) BP lowering was associated with a 46% lower risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68). Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those assigned to the intensive (versus standard) BP lowering were 66% more likely to regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31-2.11). Adjustment for LVH as a time-varying covariate did not substantially attenuate the effect of intensive BP therapy on CVD events (hazard ratio of intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64-0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment for LVH as a time-varying covariate, respectively)., Conclusions: Among patients with hypertension but no diabetes mellitus, intensive BP lowering (target systolic BP <120 mm Hg) compared with standard BP lowering (target systolic BP <140 mm Hg) resulted in lower rates of developing new LVH in those without LVH and higher rates of regression of LVH in those with existing LVH. This favorable effect on LVH did not explain most of the reduction in CVD events associated with intensive BP lowering in the SPRINT trial., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062., (© 2017 American Heart Association, Inc.)

Objective: The aim of this study was to investigate the possible correlation of serum visfatin levels with resistant hypertension (RHT)., Patients and Methods: Patients who had undergone ambulatory blood pressure measurements (ABPM) during the outpatient controls were prospectively recruited. Seventy-one patients with RHT and 94 patients with controlled hypertension (CHT) were included in the study. RHT was defined as 'uncontrolled blood pressure (BP) despite using three antihypertensive agents including a diuretic or need of four or more drugs to control BP'. The demographic properties, medications used, and laboratory parameters including visfatin levels were recorded., Results: In the RHT group, left ventricular mass index was significantly higher compared with the CHT group (108.13±26.86 vs. 89.46±24.09 g/m, P<0.01). High-sensitivity C-reactive protein and visfatin levels were significantly higher in the RHT group [4.0 (5.2) vs. 2.3 (3.0) mg/l, P<0.01, and 12.87±4.98 vs. 9.46±4.69 ng/ml, P<0.01, respectively] compared with the CHT group. In the multivariate linear regression model, visfatin level remained as an independent predictor for office systolic BP [B: 2.07, 95% confidence interval (CI): 1.17-2.98, P<0.01]; office diastolic BP (B: 0.71, 95% CI: 0.27-1.16, P<0.01); mean 24-h systolic ABPM (B: 1.46, 95% CI: 0.79-2.13, P<0.01); and mean 24-h diastolic ABPM (B: 0.88, 95% CI: 0.42-1.34, P<0.01) and was also correlated independently with left ventricular mass index (B: 3.13, 95% CI: 2.58-3.99, P<0.01)., Conclusion: In this cohort of RHT patients diagnosed with ABPM, we have found an independent correlation between higher visfatin levels and the presence of RHT and left ventricular hypertrophy.

Background: Coronary artery disease is identified in ≈80% of victims of sudden cardiac death (SCD). Because the prevention strategies and public awareness have changed during the past decades, we studied the temporal trends in the pathogenesis of SCD., Methods and Results: FinGesture (n=4031) is a prospective study designed to classify the phenotype and genotype profiles of SCD in a consecutive series of victims of SCD in Northern Finland. On the basis of Finnish law, all subjects who die suddenly undergo autopsy. We analyzed the characteristics of SCD victims and autopsy findings in 1998 to 2002, 2003 to 2007, and 2008 to 2012. Among victims of SCD as a first cardiac event (n=2697), the proportion with coronary artery disease decreased during the 2008 to 2012 time period, compared with the 2 preceding 5-year periods: 74.0% in 1998 to 2002, 73.1% in 2003 to 2007, and 66.4% in 2008 to 2012 (P<0.001). Proportion of SCDs associated with hypertensive heart disease with left ventricular hypertrophy in the absence of coronary artery disease increased from 1.7% in 1998 to 2002 to 5.8% in 2003 to 2007 and 8.9% in 2008 to 2012 (P<0.001). Similarly, myocardial fibrosis in the absence of myocarditis or left ventricular hypertrophy, or other known pathogeneses, was 6.7% in the past 5-year period compared with 2 previous 5-year periods (3.7% and 4.0%; P<0.001 between 1998-2002 and 2008-2012 and between 2003-2007 and 2008-2012)., Conclusions: The proportion of SCDs attributable to coronary artery disease, in the absence of a history of heart disease, has decreased, whereas the proportion associated with hypertensive heart disease and idiopathic fibrosis has increased during the past 15 years., (© 2016 American Heart Association, Inc.)

Background: Hypertrophic cardiomyopathy is associated with sudden cardiac death (SCD). Some studies have shown an association between risk of sudden death and left ventricular maximal wall thickness (MWT), but there are few data in patients with extreme hypertrophy. The aim of this study was to determine the relation between MWT and the risk of SCD., Methods and Results: This is a multicenter, retrospective, longitudinal cohort study of 3673 adult (≥16 years) patients, previously used to develop and validate a risk prediction model for SCD (HCM Risk-SCD [hypertrophic cardiomyopathy risk-SCD]). There was an inverted U-shaped relation between MWT and the estimated 5-year risk of SCD. In patients with MWT≥35 mm (n=47; mean age, 33 years; 81% men), there was a single SCD end point (annual rate, 0.2%; 95% confidence interval, 0.03-1.60) and 3 additional cardiovascular events during a median follow-up of 9.5 years. Compared with patients with MWT≤14 mm, those with MWT≥35 mm did not have a higher risk for SCD (hazard ratio, 0.22; 95% confidence interval, 0.03-1.65), cardiovascular death (hazard ratio, 0.66; 95% confidence interval, 0.26-1.67), or all-cause mortality (hazard ratio, 0.73; 95% confidence interval, 0.32-1.69)., Conclusions: The risk of SCD has a complex, nonlinear relationship to MWT. The pathophysiological mechanisms behind this observation require further study but implantable cardioverter defibrillator implantation should not be guided solely on the severity of left ventricular hypertrophy., (© 2016 American Heart Association, Inc.)

Homocysteine levels in the low to moderate range for cardiovascular risk have been previously associated with left ventricular cardiac hypertrophy (LVH). Electrocardiogram (ECG) derived QRS duration has also been used as an epidemiological screening marker for cardiac hypertrophy risk. QRS duration cut offs have not been previously modeled to assess homocysteine levels in community populations. Our aims are to determine if QRS duration is associated with an elevated homocysteine level in a cross-sectional Australian aging rural population.A retrospective study design utilizing a rural health diabetic screening clinic database containing observational data from the period January 9, 2002 till September 25, 2012. One hundred seventy-eight individuals (>21 years of age) from the database were included in the study. Inclusion criteria included being nondiabetic and having both a QRS duration measure and a matching homocysteine level within the same subject. All participants were from the Albury-Wodonga area, with a mean age of >64 years for both sexes.Mean population homocysteine plasma levels were 10.4 μmol/L (SD = 3.6). The mean QRS duration was 101.8 ms (SD = 17.4). Groups were stratified on the basis of QRS duration (≤120 ms [n = 157] and >120 ms [n = 21]). QRS duration subgroup (≤120 ms vs >120 ms) mean differences across homocysteine levels were 10.1 μmol/L (SD = 3.3) and 12.2 μmol/L (SD = 4.7), respectively (P = 0.016). Other ECG parameters (PQ interval, QTc interval, and QT dispersion) measurements were not significantly associated with differences in plasma homocysteine (P = not significant).We conclude that in community populations homocysteine may be moderately elevated when QRS durations are >120 ms. Small additional increases in homocysteine levels may suggest a risk factor for ECG diagnosis of LVH.

Background: Ventricular tachycardia (VT) substrate ablation usually requires extensive ablation. Scar dechanneling technique may limit the extent of ablation needed., Methods and Results: The study included 101 consecutive patients with left ventricular scar-related VT (75 ischemic patients; left ventricular ejection fraction, 36 ± 13%). Procedural end point was the elimination of all identified conducting channels (CCs) by ablation at the CC entrance followed by abolition of residual inducible VTs. By itself, scar dechanneling rendered noninducibility in 54.5% of patients; ablation of residual inducible VT increased noninducibility to 78.2%. Patients needing only scar dechanneling had a shorter procedure (213 ± 64 versus 244 ± 71 minutes; P = 0.027), fewer radiofrequency applications (19 ± 11% versus 27 ± 18%; P = 0.01), and external cardioversion/defibrillation shocks (20% versus 65.2%; P < 0.001). At 2 years, patients needing scar dechanneling alone had better event-free survival (80% versus 62%) and lower mortality (5% versus 11%). Incomplete CC-electrogram elimination was the only independent predictor (hazard ratio, 2.54 [1.06-6.10]) for the primary end point. Higher end point-free survival rates were observed in patients noninducible after scar dechanneling (log-rank P = 0.013) and those with complete CC-electrogram elimination (log-rank P = 0.013). The complications rate was 6.9%, with no deaths., Conclusions: Scar dechanneling alone results in low recurrence and mortality rates in more than half of patients despite the limited ablation extent required. Residual inducible VT ablation improves acute results, but patients who require it have worse outcomes. Recurrences are mainly related to incomplete CC-electrogram elimination., (© 2015 American Heart Association, Inc.)

This study describes the un-natural history of a 16-year-old patient, presenting with a critical bicuspid aortic valve stenosis, who was initially treated in the neonatal period and later with a valvuloplasty. This focused the attention on palliative interventions that, in young adulthood or middle age, are usually related to several complications, until heart transplantation. The other important aspect of this case is the presence of a coronary atherosclerotic plaque producing a significant obstruction, in the setting of haemodynamic acute postoperative failure caused by the sudden aortic valve laceration and insufficiency. This favoured the transmural myocardial antero-septal evolution of the myocardial ischaemic-reperfusion damage. This case is peculiar in that it presents two unrelated entities in their natural history. The coronary lesion was an unexpected finding in an adolescent with congenital heart disease. The severity of the coronary lesion became haemodynamically significant as a combination of the hypoperfusion due to the massive aortic valve regurgitation following the acute failure of the aortic valve plasty and the vasoconstriction of the eccentric speared segment. Once again, the complete understanding of grown-up patients with congenital hart disease is mandatory together with the point that a close collaboration of a multidisciplinary team is essential for appropriate operative timing and planning the most suitable treatment option. Acquired heart diseases can rarely present in association in this group of patients and need to be taken into account.

Background: Intramyocardial triglyceride (TG) turnover is reduced in pressure-overloaded, failing hearts, limiting the availability of this rich source of long-chain fatty acids for mitochondrial β-oxidation and nuclear receptor activation. This study explored 2 major dietary fats, palmitate and oleate, in supporting endogenous TG dynamics and peroxisome proliferator-activated receptor-α activation in sham-operated (SHAM) and hypertrophied (transverse aortic constriction [TAC]) rat hearts., Methods and Results: Isolated SHAM and TAC hearts were provided media containing carbohydrate with either (13)C-palmitate or (13)C-oleate for dynamic (13)C nuclear magnetic resonance spectroscopy and end point liquid chromatography/mass spectrometry of TG dynamics. With palmitate, TAC hearts contained 48% less TG versus SHAM (P=0.0003), whereas oleate maintained elevated TG in TAC, similar to SHAM. TG turnover in TAC was greatly reduced with palmitate (TAC, 46.7±12.2 nmol/g dry weight per min; SHAM, 84.3±4.9; P=0.0212), as was β-oxidation of TG. Oleate elevated TG turnover in both TAC (140.4±11.2) and SHAM (143.9±15.6), restoring TG oxidation in TAC. Peroxisome proliferator-activated receptor-α target gene transcripts were reduced by 70% in TAC with palmitate, whereas oleate induced normal transcript levels. Additionally, mRNA levels for peroxisome proliferator-activated receptor-γ-coactivator-1α and peroxisome proliferator-activated receptor-γ-coactivator-1β in TAC hearts were maintained by oleate. With these metabolic effects, oleate also supported a 25% improvement in contractility over palmitate with TAC (P=0.0202)., Conclusions: The findings link reduced intracellular lipid storage dynamics to impaired peroxisome proliferator-activated receptor-α signaling and contractility in diseased hearts, consistent with a rate-dependent lipolytic activation of peroxisome proliferator-activated receptor-α. In decompensated hearts, oleate may serve as a beneficial energy substrate versus palmitate by upregulating TG dynamics and nuclear receptor signaling., (© 2014 American Heart Association, Inc.)

Background and Purpose: The most well-known stroke risk score is the Framingham Stroke Risk Score (FSRS), which was developed during the higher stroke risk period of the 1990s and has not been validated for blacks. We assessed the performance of the FSRS among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine whether it is useful in both blacks and whites., Methods: Expected annualized stroke rates from the FSRS were compared with observed stroke rates overall and within strata defined by FSRS risk factors (age, sex, systolic blood pressure, use of antihypertensive medications, diabetes mellitus, smoking, atrial fibrillation, left ventricular hypertrophy, and prevalent coronary heart disease)., Results: Among 27 748 participants stroke-free at baseline, 715 stroke events occurred over 5.6 years of follow-up. FSRS-estimated incidence rates of stroke were 1.6× higher than observed for black men, 1.9× higher for white men, 1.7× higher for black women, and 1.7× higher for white women. This overestimation was consistent among most subgroups of FSRS factors, although the magnitude of overestimation varied by the risk factor assessed., Conclusions: Although higher FSRS was associated with higher stroke risk, the FSRS overestimated the observed stroke rates in this study, particularly in certain subgroups. This may be because of temporal declines in stroke rates, secular trends in prevention treatments, or differences in populations studied. More accurate estimates of event rates are critical for planning research, including clinical trials, and targeting health-care efforts., (© 2014 American Heart Association, Inc.)

Background: Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subsequent adverse events in a new 4-group LVH classification based on LV dilatation (high LV end-diastolic volume [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV](2/3)) in hypertensive patients., Methods and Results: In the Losartan Intervention for Endpoint Reduction (LIFE) echocardiography substudy, 939 hypertensive patients with measurable LVM at baseline were randomized to a mean of 4.8 years of losartan- or atenolol-based treatment. Patients with LVH (LVM/body surface area ≥116 and ≥96 g/m(2) in men and woman, respectively) were divided into 4 groups-concentric nondilated (increased M/EDV, normal EDV), eccentric dilated (increased EDV, normal M/EDV), concentric dilated (increased M/EDV and EDV), and eccentric nondilated (normal M/EDV and EDV)-and compared with patients with normal LVM. Time-varying LVH classes were tested for association with all-cause and cardiovascular mortality and a composite end point of myocardial infarction, stroke, heart failure, and cardiovascular death in multivariable Cox analyses. At baseline, the LVs were categorized as eccentric nondilated in 12%, eccentric dilated in 20%, concentric nondilated in 29%, concentric dilated in 14%, and normal LVM in 25%. Treatment changed the prevalence of 4 LVH groups to 23%, 4%, 5%, and 7%; 62% had normal LVM after 4 years. In time-varying Cox analyses, compared with normal LVM, those with eccentric dilated and both concentric nondilated and dilated LVH had increased risks of all-cause or cardiovascular mortality or the composite end point, whereas the eccentric nondilated group did not., Conclusions: Hypertensive patients with relatively mild LVH without either increased LV volume or concentricity have similar risk of all-cause mortality or cardiovascular events because hypertensive patients with normal LVM seem to be a low-risk group., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00338260., (© 2014 American Heart Association, Inc.)

Background: Cardiovascular magnetic resonance has provided important information on the diagnosis and risk stratification of hypertrophic cardiomyopathy (HCM) in adults; however, comparable data are absent for HCM in children. The study was performed to evaluate cardiovascular magnetic resonance characteristics in children with idiopathic HCM., Methods and Results: Cardiovascular magnetic resonance was performed in 71 consecutive children with idiopathic HCM (age, 12.8±4.1 years; 46 boys and 25 girls). The left ventricular (LV) parameters indexed by body surface area were calculated and compared with those in 71 healthy children (age, 13.1±3.3 years; 51 boys and 20 girls). Among those with HCM, concentric LV hypertrophy occurred in 9 patients (12.7%): in 2 children, it progressed into end-stage phase. The prevalence of late gadolinium enhancement (LGE) was 73%, and the extent of LGE was 10.4±8.3% of LV mass. Children with HCM with LGE had greater LV mass indexed (112.7±57.9 versus 70.3±37.4 g/m(2); P=0.025) but had no significant difference in maximal LV wall thickness indexed (19.4±6.3 versus 18.1±7.9 mm/m(2); P=0.513). In addition, the hazard ratio of adverse events for the extent of LGE was 1.1 (P=0.004). The follow-up (2.4±1.6 years) demonstrated that LGE was associated with adverse events in children with HCM (log-rank; P=0.029)., Conclusions: The prevalence and extent of LGE in children with HCM approximate to those in adults with HCM. Furthermore, children with HCM with LGE tend to have adverse events, and larger researches with longer follow-up are required.

Background: Impaired diastolic function and increased left ventricular mass are common findings in hypertensive patients and may occur early in the natural history of essential hypertension. In this study, we aimed to investigate the relationship between diastolic function parameters and coronary artery calcification (CAC) in hypertensive patients., Methods: The study was carried out on 128 asymptomatic hypertensive patients (58 women and 70 men). Diastolic function was evaluated by the mean ratio of peak of early (E) and peak of late (A) mitral inflow (E/A ratio), deceleration time, and isovolumic relaxation time. Patients were classified into two groups on the basis of the presence of CAC and were also divided into two groups on the basis of the presence of left ventricular hypertrophy., Results: The mean E/A ratio, deceleration time, and isovolumic relaxation time of CAC+ patients were 0.87±0.34, 143.93±29.11, and 87.86±16.34 ms, respectively, and 0.92±0.31, 140.80±27.90, 86.40±13.96 ms in CAC- patients, respectively. Diastolic function was not found to be related to the presence of CAC. The mean left ventricular mass index (LVMI) was determined to be 115.60±18.16 g/m in CAC+ patients and 104.93±29.54 g/m in CAC- patients, and the correlation between the presence of CAC and LVMI was statistically significant (P=0.019). A multivariate analysis showed that the E/A ratio was inversely related to age, blood pressure, pulse pressure, and LVMI (P<0.001) in CAC+ patients. In stepwise regression analysis, LVMI was the strongest determinant for the E/A ratio in CAC+ hypertensive patients (R=0.26, P<0.001)., Conclusion: Our results identify that diastolic functions are not affected by the presence of CAC in hypertensive patients; however, left ventricular diastolic function is impaired in the presence of left ventricular hypertrophy.

Background: Prevalent atrial fibrillation (AF) is associated with a higher sudden cardiac death (SCD) rate in some populations, and incident AF predicts increased mortality risk in the general population and after myocardial infarction. However, the relationship of SCD to new-onset AF is unclear., Methods and Results: The relationship of SCD to new-onset AF was evaluated in 8831 hypertensive patients with electrocardiographic left ventricular hypertrophy with no history of AF, in sinus rhythm on their baseline electrocardiogram, randomly assigned to losartan- or atenolol-based treatment. During 4.7±1.1 years mean follow-up, new-onset AF occurred in 701 patients (7.9%) and SCD in 151 patients (1.7%). In univariate Cox analyses, new-onset AF was associated with a >4-fold higher risk of SCD (hazard ratio, 4.69; 95% CI interval, 2.96-7.45; P<0.001). In multivariate Cox analyses adjusting for age, sex, race, diabetes mellitus, history of heart failure, myocardial infarction, ischemic heart disease, stroke, smoking, serum high-density lipoprotein cholesterol, creatinine, glucose, and urine albumin/creatinine ratio as standard risk factors, and for incident myocardial infarction, in-treatment use of digoxin, systolic and diastolic pressure, heart rate, QRS duration, Cornell voltage-duration product, and Sokolow-Lyon voltage left ventricular hypertrophy treated as time-varying covariates, new-onset AF remained associated with a >3-fold increased risk of SCD (hazard ratio, 3.13; 95% confidence interval, 1.87-5.24; P<0.001)., Conclusions: Development of new-onset AF identifies hypertensive patients at increased risk of SCD., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00338260.

Rationale: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring protein, junctophilin-2. MicroRNA (miR)-24, a junctophilin-2 suppressing miR, is upregulated in hypertrophied and failing cardiomyocytes., Objective: To test whether miR-24 suppression can protect the structural and functional integrity of L-type Ca(2+) channel-ryanodine receptor signaling in hypertrophied cardiomyocytes., Methods and Results: In vivo silencing of miR-24 by a specific antagomir in an aorta-constricted mouse model effectively prevented the degradation of heart contraction, but not ventricular hypertrophy. Electrophysiology and confocal imaging studies showed that antagomir treatment prevented the decreases in L-type Ca(2+) channel-ryanodine receptor signaling fidelity/efficiency and whole-cell Ca(2+) transients. Further studies showed that antagomir treatment stabilized junctophilin-2 expression and protected the ultrastructure of T-tubule-sarcoplasmic reticulum junctions from disruption., Conclusions: MiR-24 suppression prevented the transition from compensated hypertrophy to decompensated hypertrophy, providing a potential strategy for early treatment against heart failure.

Background and Purpose: Familial transmission of stroke and myocardial infarction (MI) is partially mediated by transmission of cerebrovascular and cardiovascular risk factors. We examined relationships between family risk of stroke and MI with risk factors for these phenotypes., Methods: A cross-sectional association between the stratified log-rank family score for stroke and MI with prevalent risk factors was assessed in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort., Results: Individuals in the fourth quartile of stratified log-rank family scores for stroke were more likely to have prevalent risk factors including hypertension (OR, 1.43; 95% CI, 1.30-1.58), left ventricular hypertrophy (OR, 1.42; 95% CI, 1.16-1.42), diabetes (OR, 1.26; 95% CI, 1.12-1.43), and atrial fibrillation (OR, 1.23; 95% CI, 1.03-1.45) compared with individuals in the first quartile. Likewise, individuals in the fourth quartile of stratified log-rank family scores for MI were more likely to have prevalent risk factors including hypertension (OR, 1.57; 95% CI, 1.27-1.94) and diabetes (OR, 1.29; 95% CI, 1.12-1.43) than the first quartile. In contrast to stroke, the family risk score for MI was associated with dyslipidemia (OR, 1.38; 95% CI, 1.23-1.55) and overweight/obesity (OR, 1.22; 95% CI, 1.10-1.37)., Conclusions: Family risk of stroke and MI is strongly associated with the majority of risk factors associated with each disease. Family history and genetic studies separating nonspecific contributions of intermediate phenotypes from specific contributions to the disease phenotype may lead to a more thorough understanding of transmission for these complex disorders.

Background: The prognostic impact of ECG left ventricular strain and left ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well described., Methods and Results: Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve replacement, or cardiovascular death. The predictive value of ECG left ventricular strain (defined as T-wave inversion in leads V(4) through V(6)) and LVH, assessed by Sokolow-Lyon voltage criteria (R(V5-6)+S(V1) ≥35 mV) and Cornell voltage-duration criteria {[RaVL+S(V3)+(6 mV in women)]×QRS duration ≥2440 mV · ms}, was evaluated by adjustment for other prognostic covariates. A total of 1533 patients were followed for 4.3±0.8 years (6592 patient-years of follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340 patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left ventricular strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval, 1.4-6.8; P=0.004). Similarly, ECG LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of heart failure (95% confidence interval, 2.0-16.8), 2.0-fold higher risk of aortic valve replacement (95% confidence interval, 1.3-3.1; both P=0.001), and 2.5-fold higher risk of a combined end point of myocardial infarction, heart failure, or cardiovascular death (95% confidence interval, 1.3-4.9; P=0.008)., Conclusions: ECG left ventricular strain and LVH were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis., Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00092677., (© 2011 American Heart Association, Inc.)

Rationale: Pressure overload cardiac hypertrophy, a risk factor for heart failure, is associated with reduced mitochondrial fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) proteins that correlate in rodents with reduced PGC-1α expression., Objective: To determine the role of PGC-1β in maintaining mitochondrial energy metabolism and contractile function in pressure overload hypertrophy., Methods and Results: PGC-1β deficient (KO) mice and wildtype (WT) controls were subjected to transverse aortic constriction (TAC). Although LV function was modestly reduced in young KO hearts, there was no further decline with age so that LV function was similar between KO and WT when TAC was performed. WT-TAC mice developed relatively compensated LVH, despite reduced mitochondrial function and repression of OXPHOS and FAO genes. In nonstressed KO hearts, OXPHOS gene expression and palmitoyl-carnitine-supported mitochondrial function were reduced to the same extent as banded WT, but FAO gene expression was normal. Following TAC, KO mice progressed more rapidly to heart failure and developed more severe mitochondrial dysfunction, despite a similar overall pattern of repression of OXPHOS and FAO genes as WT-TAC. However, in relation to WT-TAC, PGC-1β deficient mice exhibited greater degrees of oxidative stress, decreased cardiac efficiency, lower rates of glucose metabolism, and repression of hexokinase II protein., Conclusions: PGC-1β plays an important role in maintaining baseline mitochondrial function and cardiac contractile function following pressure overload hypertrophy by preserving glucose metabolism and preventing oxidative stress.

Background: Polymorphisms in 11-β hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) have been reported to be associated with obesity-related cardiovascular risk factors, such as type II diabetes and hypertension. Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular death associated with these factors but has significant additional heritability, the cause of which is undetermined. The 11β-HSD1 is believed to maintain tonic inhibition of the mineralocorticoid receptor in cardiomyocytes, and mineralocorticoid receptor activation is involved in the pathophysiology of LVH. We assessed the association between polymorphisms in the HSD11B1 gene and left ventricular mass (LVM) in 248 families ascertained through a proband with hypertension., Methods and Results: LVM was measured by electrocardiography and echocardiography in 868 and 829 participants, respectively. Single-nucleotide polymorphisms (SNPs) tagging common variation in the HSD11B1 gene were genotyped by mass spectrometry. The rs846910 SNP, which lies in the flanking region 5' to exon 1B of HSD11B1, was associated with LVM both by electrocardiography (≈5% lower LVM per copy of the rare allele, P=0.02) and by echocardiography (≈10% lower LVM per copy of the rare allele, P=0.003). Genotype explained 1% to 2% of the population variability in LVM, or approximately 5% of the heritable fraction. There were no significant associations between any HSD11B1 SNP and blood pressure or body mass index that could have confounded the association with LVM., Conclusions: Genotype at HSD11B1 has a small, but significant effect on LVM, apparently independently of any effect on obesity-related traits. These findings suggest a novel action of 11β-HSD1 in the human cardiomyocyte, which may be of therapeutic importance.

Background: Blacks have a higher prevalence of heart failure (HF) than nonblacks, possibly reflecting a greater burden of HF risk factors, including hypertension. Although HF incidence is significantly higher in blacks during long-term follow-up of young adults, the relationship of incident HF to race in hypertensive patients undergoing treatment is unclear., Methods and Results: Incident HF was evaluated in 497 black and 8199 nonblack hypertensive patients with no history of HF randomly assigned to losartan- or atenolol-based treatment. During 4.7±1.1 years mean follow-up, HF hospitalization occurred in 265 patients (3.0%); 5-year HF incidence was significantly greater in black than nonblack patients (7.0 versus 3.1%, P<0.001). In Cox multivariate analyses adjusting for randomized treatment, age, sex, the presence of the strain pattern on the baseline ECG, and other HF risk factors treated as standard covariates, and for incident myocardial infarction, in-treatment QRS duration, diastolic and systolic pressure, Cornell product, and Sokolow-Lyon voltage criteria for left ventricular hypertrophy (LVH) treated as time-varying covariates, black race remained associated with a 130% increased risk of developing new HF (hazard ratio 2.30, 95% confidence interval 1.24 to 4.28)., Conclusions: Incident HF is substantially more common among black than nonblack hypertensive patients. The increased risk of developing new HF in blacks persists after adjusting for the higher prevalence of HF risk factors in blacks, for treatment effects and in-treatment blood pressure, and for the known predictive value of the ECG strain pattern and in-treatment ECG LVH and QRS duration for incident HF in this population. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00338260.

Background: Data regarding the familial aggregation of left ventricular (LV) geometry and its relations to parental heart failure (HF) are limited., Methods and Results: We evaluated concordance of LV geometry within 1093 nuclear families in 5758 participants of the original (parents) (n=2351) and offspring (n=3407) cohorts of the Framingham Heart Study undergoing routine echocardiography in mid- to late adulthood. LV geometry was categorized based on cohort- and sex-specific 80th percentile cutoffs of LV mass and relative wall thickness (RWT) into normal (both <80th percentile), concentric remodeling (LV mass <80th percentile; RWT >80th percentile), concentric hypertrophy (both >80th percentile), and eccentric hypertrophy (LV mass >80th percentile; RWT <80th percentile). Within nuclear families, LV geometry was concordant among related pairs (parent-child, sibling-sibling) (P=0.0015) but not among unrelated spousal pairs (P=0.60), a finding that remained unchanged after adjusting for clinical covariates known to influence LV remodeling (age, systolic blood pressure, body mass index), excluding individuals with prevalent HF and myocardial infarction, and varying the thresholds for defining LV geometry. The prevalence of abnormal LV geometry was higher in family members of affected individuals, with recurrence risks of 1.4 for concentric remodeling (95% CI, 1.2 to 1.7) and eccentric hypertrophy (95% CI, 1.1 to 1.8) and 3.9 (95% CI, 3.2 to 4.6) for concentric hypertrophy. In a subset of 1497 offspring, we observed an association between parental HF (n=458) and eccentric hypertrophy in offspring (P<0.0001)., Conclusions: Our investigation of a 2-generational community-based sample demonstrates familial aggregation of LV geometry, with the greatest recurrence risk for concentric LV geometry, and establishes an association between eccentric LV geometry and parental HF.

Background and Aim: Limited information is available on the association between left ventricular (LV) geometric patterns defined according to updated criteria and blood pressure (BP) levels and extra-cardiac organ damage (OD) in human hypertension. Thus, in untreated essential hypertensives we assessed the relationship between LV geometry, ambulatory BP and markers of vascular and renal OD., Methods: A total of 669 hypertensives were categorized in four groups according to LV geometric patterns defined by two sets of sex-specific criteria (i.e. LV mass indexed to body surface area and height) and by the relative wall thickness (RWT) partition value of 0.42. Ambulatory BP variables were derived from two 24-h monitoring sessions performed within 4 weeks., Results: Lower clinic and ambulatory BP values were associated with normal LV geometry, intermediate values with either LV concentric remodelling or eccentric LV hypertrophy (LVH) and higher values with concentric LVH, regardless of the criteria used to categorize these cardiac phenotypes. A decrease in nocturnal BP dip occurred from normal LV geometry to concentric LVH and this was associated with a parallel increase in the prevalence of carotid and renal OD, which was highest in concentric LVH. In a multivariate analysis age (beta=0.204, P<0.0001), followed by LDL cholesterol (beta=0.113, P=0.004), and night-time BP (beta=0.101, P=0.009) turned out to be the best independent correlates of RWT., Conclusion: These findings indicate that LV geometric patterns, regardless of categorization criteria, reflect different degrees of BP load and subclinical extra-cardiac alterations and may be regarded, in addition to absolute values of LV mass, as a reliable marker of cardiovascular (CV) risk.

Background: The impact of alcohol septal ablation (ASA)-induced scar is not known. This study sought to examine the long-term outcome of ASA among patients with obstructive hypertrophic cardiomyopathy., Methods and Results: Ninety-one consecutive patients (aged 54+/-15 years) with obstructive hypertrophic cardiomyopathy underwent ASA. Primary study end point was a composite of cardiac death and aborted sudden cardiac death including appropriate cardioverter-defibrillator discharges for fast ventricular tachycardia/ventricular fibrillation. Secondary end points were noncardiac death and other nonfatal complications. Outcomes of ASA patients were compared with 40 patients with hypertrophic cardiomyopathy who underwent septal myectomy. During 5.4+/-2.5 years, primary and/or secondary end points were seen in 35 (38%) ASA patients of whom 19 (21%) patients met the primary end point. The 1-, 5-, and 8-year survival-free from the primary end point was 96%, 86%, and 67%, respectively in ASA patients versus 100%, 96%, and 96%, respectively in myectomy patients during 6.6+/-2.7 years (log-rank, P=0.01). ASA patients had a approximately 5-fold increase in the estimated annual primary end point rate (4.4% versus 0.9%) compared with myectomy patients. In a multivariable model including a propensity score, ASA was an independent predictor of the primary end point (unadjusted hazard ratio, 5.2; 95% CI, 1.2 to 22.1; P=0.02 and propensity score-adjusted hazard ratio, 6.1; 95% CI, 1.4 to 27.1; P=0.02)., Conclusions: This study shows that ASA has potentially unwanted long-term effects. This poses special precaution, given the fact that ASA is practiced worldwide at increasing rate. We recommend myectomy as the preferred intervention in patients with obstructive hypertrophic cardiomyopathy.

Background: Data regarding the relationships of diabetes, insulin resistance, and subclinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations., Methods and Results: A total of 1603 Framingham Heart Study Offspring participants (age, 64+/-9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction, cardiac output, and left atrial size. Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, prediabetes, and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hour insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht(2.7) and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with prediabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable adjustment only in men. LVM/LVEDV was significantly associated with 2-hour insulin in men only, and RWT was significantly associated with 2-hour glucose in women only. In multivariable stepwise selection analyses, the inclusion of body mass index led to a loss in statistical significance., Conclusions: Although insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling.

Background: Congestive heart failure (CHF) is associated with a change in cardiac energy metabolism. However, the mechanism by which this change is induced and causes the progression of CHF is unclear., Methods and Results: We analyzed the cardiac energy metabolism of Dahl salt-sensitive rats fed a high-salt diet, which showed a distinct transition from compensated left ventricular hypertrophy to CHF. Glucose uptake increased at the left ventricular hypertrophy stage, and glucose uptake further increased and fatty acid uptake decreased at the CHF stage. The gene expression related to glycolysis, fatty acid oxidation, and mitochondrial function was preserved at the left ventricular hypertrophy stage but decreased at the CHF stage and was associated with decreases in levels of transcriptional regulators. In a comprehensive metabolome analysis, the pentose phosphate pathway that regulates the cellular redox state was found to be activated at the CHF stage. Dichloroacetate (DCA), a compound known to enhance glucose oxidation, increased energy reserves and glucose uptake. DCA improved cardiac function and the survival of the animals. DCA activated the pentose phosphate pathway in the rat heart. DCA activated the pentose phosphate pathway, decreased oxidative stress, and prevented cell death of cultured cardiomyocytes., Conclusions: Left ventricular hypertrophy or CHF is associated with a distinct change in the metabolic profile of the heart. DCA attenuated the transition associated with increased energy reserves, activation of the pentose phosphate pathway, and reduced oxidative stress.

Objective: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol., Methods: We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol., Results: ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH., Conclusion: ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.

Objectives: Conducting system defects are common in patients with aortic valve disease. Aortic valve replacement may result in further conduction abnormalities requiring permanent pacemaker implantation. The aim of our study was to identify the incidence and predictors for postoperative 30-day permanent pacemaker implantation in patients undergoing isolated aortic valve replacement, and the effect of an accurate surgical technique in order to prevent permanent pacemaker implantation., Methods: Data from 261 consecutive patients (mean age 69 +/- 12 years, 136 men) undergoing isolated aortic valve replacement from January 2004 to January 2008 were analyzed retrospectively. Indications for aortic valve replacement were aortic valve stenosis (n = 156), stenoinsufficiency (n = 63), regurgitation (n = 42). Aortic bicuspid valve was present in 25% of cases (n = 64), redo operation was the indication in 7% (n = 18). Preoperative conducting system disease, defined as first-degree atrioventricular block, left or right bundle-branch block or left anterior hemiblock, was present in 25.6% (n = 67) of patients. An accurate surgical technique for debridement of calcific material was performed., Results: In-hospital mortality was 0.8% (2 out of 261 patients). Postoperatively, 8 out of 261 patients (3%) required permanent pacemaker implantation, for second-degree (n = 1) or complete atrioventricular block (n = 7). Incidence of permanent pacemaker implantation was similar for patients either with or without preoperative conducting system disease (25 vs. 25.7%, P = NS). Independent predictors of permanent pacemaker implantation were greater preoperative end-systolic diameter (P = 0.026) and left ventricular septum hypertrophy (P = 0.041)., Conclusions: Need of permanent pacemaker implantation after aortic valve replacement seems to be related more to preoperative advanced aortic valve disease rather than pre-existing conducting system abnormalities. An accurate surgical technique for aortic valve replacement probably helps to prevent further impairment of conducting system function requiring early postoperative permanent pacemaker implantation.

Background: Age and left ventricular (LV) hypertrophy are risk factors for the development of LV dysfunction and congestive heart failure. Our goal was to study the relationships of LV mass and age with myocardial dyssynchrony among asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis., Methods and Results: A total of 1100 individuals underwent tagged magnetic resonance imaging. Regional LV function was analyzed with the use of harmonic phase imaging. Time to peak systolic circumferential strain and strain rate were measured in 12 segments, and myocardial dyssynchrony was expressed as the SD of time to peak strain and strain rate. Relationships of age, LV mass, and myocardial perfusion with timing of strain, strain rate, and dyssynchrony were studied. There was a positive relationship between age and time to peak strain before (regression coefficient=0.37 ms/year of age; 95% confidence interval, 0.05 to 0.70; P=0.025) and after adjustment for demographic characteristics and risk factors (P=0.007). Positive associations between age and SD of time to peak strain (regression coefficient=0.33 ms/year of age; P=0.002) and SD of time to peak systolic strain rate were documented (P=0.045). Importantly, we found that LV mass index is directly related to time to peak strain (P<0.001), time to peak strain rate, and the SD of time to strain rate (P=0.001 for all). Finally, decreased myocardial perfusion at rest was associated with delayed contraction and increased extent of dyssynchrony., Conclusions: In asymptomatic individuals, age, increased LV mass, and decreased myocardial perfusion are related to delayed myocardial contraction and greater extent of dyssynchrony. Increased dyssynchrony may mediate the association of myocardial dysfunction with age and LV hypertrophy.