Greater Left Ventricular Wall Thickness Research Articles

Relationship of Subendocardial Perfusion to Myocardial Injury, Cardiac Structure, and Clinical Outcomes Among Patients With Hypertension.

Coronary microvascular dysfunction has been implicated in the development of hypertensive heart disease and heart failure, with subendocardial ischemia identified as a driver of sustained myocardial injury and fibrosis. We aimed to evaluate the relationships of subendocardial perfusion with cardiac injury, structure, and a composite of major adverse cardiovascular and cerebral events consisting of death, heart failure hospitalization, myocardial infarction, and stroke. Layer-specific blood flow and myocardial flow reserve (MFR; stress/rest myocardial blood flow) were assessed by 13N-ammonia perfusion positron emission tomography in consecutive patients with hypertension without flow-limiting coronary artery disease (summed stress score <3) imaged at Brigham and Women's Hospital (Boston, MA) from 2015 to 2021. In this post hoc observational study, biomarkers, echocardiographic parameters, and longitudinal clinical outcomes were compared by tertiles of subendocardial MFR (MFRsubendo). Among 358 patients, the mean age was 70.6±12.0 years, and 53.4% were male. The median MFRsubendo was 2.57 (interquartile range, 2.08-3.10), and lower MFRsubendo was associated with older age, diabetes, lower renal function, greater coronary calcium burden, and higher systolic blood pressure (P<0.05 for all). In cross-sectional multivariable regression analyses, the lowest tertile of MFRsubendo was associated with myocardial injury and with greater left ventricular wall thickness and volumes compared with the highest tertile. Relative to the highest tertile, low MFRsubendo was independently associated with an increased rate of major adverse cardiovascular and cerebral events (adjusted hazard ratio, 2.99 [95% CI, 1.39-6.44]; P=0.005) and heart failure hospitalization (adjusted hazard ratio, 2.76 [95% CI, 1.04-7.32; P=0.042) over 1.1 (interquartile range, 0.6-2.8) years median follow-up. Among patients with hypertension without flow-limiting coronary artery disease, impaired MFRsubendo was associated with cardiovascular risk factors, elevated cardiac biomarkers, cardiac structure, and clinical events.

Anatomical, functional and prognostic correlates of resting coronary flow velocity in patients with hypertrophic cardiomyopathy

Abstract Background The clinical significance of baseline peak diastolic coronary flow velocity (CFV) in the left anterior descending coronary artery (LAD) has not been investigated yet in patients with hypertrophic cardiomyopathy (HCM). Aim To assess the anatomical, functional and prognostic correlates of baseline LAD CFV in HCM. Methods 384 consecutive adult HCM patients (age=52+15 years, 164 [43%] females) with no known coronary artery disease from 8 centers in 5 countries were prospectively analyzed. All patients underwent comprehensive transthoracic echocardiography including CFV measurement with pulse wave Doppler in the mid-distal LAD. All patients had preserved left ventricular (LV) function. LV force was calculated as (peak instantaneous LV outflow tract gradient+systolic blood pressure)/LV end-systolic volume. Patients were followed for a median of 50 months (IQ range 18-97 months), the outcome measure was a composite endpoint of all-cause death and acute heart failure. Results The mean CFV was 36±11 cm/s. CFV was positively correlated with LV maximal wall thickness (r=0.375, p&amp;lt;0.001), LV maximal septal thickness (r=0.320, p&amp;lt;0.001), resting LV outflow tract gradient (r=0.274, p&amp;lt;0.001), LV force (r=0.227, p&amp;lt;0.001), mean E/e’ (r=0.479, p&amp;lt;0.001) and heart rate (r=0.221, p&amp;lt;0.001). During follow-up, 54 events occurred (33 all-cause deaths and 21 acute heart failures). Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (&amp;gt;31 cm/s) to predict the composite endpoint. Patients with CFV &amp;gt;31 cm/s had a significantly worse 10-year event-free survival compared to those with CFV ≤31 cm/s, see Figure. Conclusion Higher resting LAD CFV is associated with greater LV wall thickness, higher LV outflow tract gradient, faster heart rate and more elevated left ventricular filling pressures in HCM. Elevated resting CFV may indicate a coronary microcirculation dysfunction either primary or secondary to anatomical (septal hypertrophy), functional (increased myocardial oxygen demand), or autonomic (increased sympathetic drive) determinants. Whatever the underlying endotype, high resting CFV is related to worse prognosis in the long term.Figure.

IMPACT OF DIABETES MELLITUS ON ARTERIAL STIFFNESS, AND PULSATILE HEMODYNAMICS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION

Objective: The aim of the current study was to characterize different parameters of arterial stiffness and pulsatile hemodynamics in patients with arterial hypertension and metabolic syndrome according the presence of diabetes mellitus and diastolic dysfunction. Design and method: 121 consecutive patients with left ventricular ejection fraction &gt; 40% were included in the study. LV diastolic function was assessed using pulsed wave Doppler on transthoracic echocardiography. Brachial-ankle pulse wave velocity (baPWV) and the cardio-ankle vascular index (CAVI) was measured using a VaSera VS-1500® device (Fukuda Denshi). Ambulatory BP monitoring over 24 hours was performed using the Mobilograph device (IEM, Stolberg, Germany) which measures brachial and central (aortic) BP, as well as time-resolved waveforms, allowing for ambulatory pulse wave analysis (including wave separation into forward and backward waves and reflection magnitude) Results: Among 121 patients included, diabetes mellitus was present in 55 (54.5%) and diastolic dysfunction in 54 (45.4%). The presence of impaired myocardial relaxation on echocardiography was associated with markedly increase of arterial stiffness parameters – CAVI (8.7 vs 8.1, p = 0.03), PWV (8.8 vs 7.9, p = 0.001), central hemodynamics - central SBP (129.4 vs 114 mmHg, p&lt;0.001), cardiac output and total peripheral resistance (1.34 vs 1.25, p = 0.001) and pulsatile hemodynamics - with reduced reflection magnitude (60.7 vs 63, p = 0.04). Diabetic subjects with HFpEF exhibited a markedly greater left ventricular wall thickness and left atrium size on echocardiography. Pronounced aortic stiffening was also observed in the diabetic group (pulse wave velocity, 8.7 vs 7.9, p, 0.001; cardio-ankle vascular index, 9.1 vs 7.8, p&lt;0.001), with an adverse pulsatile hemodynamic profile characterized by increased forward and backward wave amplitude and reduced reflection magnitude (61 vs 64.8, p = 0.05). Conclusions: The presence of diastolic dysfunction is associated with changes of arterial stiffness and pulsatile hemodynamics. Diabetes mellitus is a key determinant of left ventricular remodeling, arterial stiffness, adverse pulsatile hemodynamics, and ventricular-arterial interactions in HFpEF.

Sphingosine-1-phosphate levels are inversely associated with left ventricular and atrial chamber volume and cardiac mass in men

AimsSphingosine-1-phosphate (S1P) is a signaling lipid, which is involved in several cellular processes including cell growth, proliferation, migration and apoptosis. The associations of serum S1P levels with cardiac geometry and function are still not clear. We investigated the associations of S1P with cardiac structure and systolic function in a population-based sample.Methods and resultsWe performed cross-sectional analyses of 858 subjects (467 men; 54.4%), aged 22 to 81 years, from a sub-sample of the population-based Study of Health in Pomerania (SHIP-TREND-0). We analyzed the associations of serum S1P with structural and systolic function left ventricular (LV) and left atrial (LA) parameters as determined by magnetic resonance imaging (MRI) using sex-stratified multivariable-adjusted linear regression models. In men, MRI data showed that a 1 µmol/L lower S1P concentration was associated with an 18.1 mL (95% confidence interval [CI] 3.66–32.6; p = 0.014) larger LV end-diastolic volume (LVEDV), a 0.46 mm (95% CI 0.04–0.89; p = 0.034) greater LV wall thickness (LVWT) and a 16.3 g (95% CI 6.55–26.1; p = 0.001) higher LV mass (LVM). S1P was also associated with a 13.3 mL/beat (95% CI 4.49–22.1; p = 0.003) greater LV stroke volume (LVSV), an 18.7 cJ (95% CI 6.43–30.9; p = 0.003) greater LV stroke work (LVSW) and a 12.6 mL (95% CI 1.03–24.3; p = 0.033) larger LA end-diastolic volume (LAEDV). We did not find any significant associations in women.ConclusionsIn this population-based sample, lower levels of S1P were associated with higher LV wall thickness and mass, larger LV and LA chamber sizes and greater stroke volume and work of the LV in men, but not in women. Our results indicate that lower levels of S1P were associated with parameters related with cardiac geometry and systolic function in men, but not in women.Graphical abstract

Left Atrial Reservoir Strain-Based Left Ventricular Diastolic Function Grading and Incident Heart Failure in Hypertrophic Cardiomyopathy

The echocardiographic assessment of left ventricular (LV) diastolic dysfunction (LVDD) in patients with hypertrophic cardiomyopathy is complex and not well-established. We investigated whether the left atrial reservoir strain (LARS) could be used to categorize LVDD and whether this grading is predictive of heart failure (HF) events in hypertrophic cardiomyopathy. A total of 414 patients with hypertrophic cardiomyopathy (aged 58.3±12.8 years; 65.7% male) were categorized using LARS-defined LVDD (LARS-DD) grades: ≥35% (grade 0), ≥24% to <35%, ≥19% to <24%, and <19% (grade 3). Patients were followed for a median of 6.9 years to assess hospitalization for HF or HF-related death. An increase in LARS-DD grade was associated with worse conventional echocardiographic parameters of LVDD, such as lower e', higher E/e' ratio, greater maximum tricuspid regurgitation velocity, and restrictive mitral inflow pattern. Higher LARS-DD grade was also associated with parameters reflecting increased LV filling pressure, such as greater LV wall thickness, greater extent of fibrosis, obstructive physiology, and decreased LV longitudinal strain. Furthermore, higher LARS-DD grade was associated with worse HF-free survival (log-rank P<0.001). Patients with LARS-DD grades 0, 1, 2, and 3 showed 10-year HF-free survival of 100%, 91.6%, 84.1%, and 67.5%, respectively. LARS-DD grade was an independent predictor of HF events after adjusting for clinical and echocardiographic variables (hazard ratio, 1.53 [95% CI, 1.03-2.28], per 1-grade increase). The LARS-DD grade also had incremental prognostic value for incident HF events over the traditional echocardiographic LVDD parameters and grading system. The prognostic value of advanced LARS-DD grade was consistent in sensitivity analyses and various patient subgroups. LARS can be used as a simple single or supplemental index to categorize LV diastolic function and predict HF events in hypertrophic cardiomyopathy.

Race- and Gender-Based Differences in Cardiac Structure and Function and Risk of Heart Failure

BackgroundAlthough heart failure (HF) risk and cardiac structure/function reportedly differ according to race and gender, limited data exist in late life when risk of HF is highest. ObjectivesThe goal of this study was to evaluate race/gender–based differences in HF risk factors, cardiac structure/function, and incident HF in late life. MethodsThis analysis included 5,149 HF-free participants from ARIC (Atherosclerosis Risk In Communities), a prospective epidemiologic cohort study, who attended visit 5 (2011-2013) and underwent echocardiography. Participants were subsequently followed up for a median 5.5 years for incident HF/death. ResultsPatients’ mean age was 75 ± 5 years, 59% were women, and 20% were Black. Male gender and Black race were associated with lower mean left ventricular ejection fraction. Black race was also associated with greater left ventricular wall thickness and concentricity, differences that persisted after adjusting for cardiovascular comorbidities. After adjusting for cardiovascular comorbidities, men were at higher risk for HF and heart failure with reduced ejection fraction (HFrEF) in Black participants compared with White participants (HF: HR of 2.36 [95% CI: 1.37-4.08] vs 1.16 [95% CI: 0.89-1.51], interaction P = 0.016; HFrEF: HR of 3.70 [95% CI: 1.72-7.95] vs 1.55 [95% CI: 1.01-2.37] respectively, interaction P = 0.039). Black race was associated with a higher incidence of HF overall and HFrEF in men only (HF: 1.65 [95% CI: 1.07-2.53] vs 0.76 [95% CI: 0.49-1.17]; HFrEF: HR of 2.55 [95% CI: 1.46-4.44] vs 0.91 [95% CI: 0.46-1.83]). No race/gender–based differences were observed in risk of incident heart failure with preserved ejection fraction. ConclusionsAmong older persons free of HF, men and Black participants exhibit worse systolic performance and are at heightened risk for HFrEF, whereas the risk of heart failure with preserved ejection fraction is similar across gender and race groups.

Clinical Implications of the Amyloidogenic V122I Transthyretin Variant in the General Population

BackgroundThe V122I variant in transthyretin (TTR) is the most common amyloidogenic mutation worldwide. The aim of this study is to describe the cardiac phenotype and risk for adverse cardiovascular outcomes of young V122I TTR carriers in the general population. Methods and ResultsTTR genotypes were extracted from whole-exome sequence data in participants of the Dallas Heart Study. Participants with African ancestry, available V122I TTR genotypes (N = 1818) and either cardiac magnetic resonance imaging (n = 1364) or long-term follow-up (n = 1532) were included. The prevalence of V122I TTR carriers (45 ± 10 years) was 3.2% (n/N = 59/1818). The V122I TTR carriers had higher baseline left ventricular wall thickness (8.52 ± 1.82 vs 8.21 ± 1.62 mm, adjusted P = .038) than noncarriers, but no differences in other cardiac magnetic resonance imaging measures (P > .05 for all). Although carrier status was not associated with amino terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline (P = .79), V122I TTR carriers had a greater increase in NT-proBNP on follow-up than noncarriers (median 28.5 pg/mL, interquartile range 11.4–104.1 pg/mL vs median 15.9 pg/mL, interquartile range 0.0–43.0 pg/mL, adjusted P = .018). V122I TTR carriers were at a higher adjusted risk of heart failure (hazard ratio 3.82, 95% confidence interval 1.80–8.13, P < .001), cardiovascular death (hazard ratio 2.65, 95% confidence interval 1.14–6.15, P = .023), and all-cause mortality (hazard ratio 1.95, 95% confidence interval 1.08–3.51, P = .026) in comparison with noncarriers. ConclusionsV122I TTR carrier status was associated with a greater increase in NT-proBNP, slightly greater left ventricular wall thickness, and a higher risk for heart failure, cardiovascular death, and all-cause mortality. These findings suggest the need to develop amyloidosis screening strategies for V122I TTR carriers.

Association of Left Ventricular Hypertrophy and Atrial Fibrillation with Hemorrhagic Evolution of Small Vessel Disease

ObjectivesCerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood. Materials and MethodsThis retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography. ResultsIn multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18–0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated. ConclusionsMost SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).

Loss of Rubicon ameliorates doxorubicin-induced cardiotoxicity through enhancement of mitochondrial quality

BackgroundThe therapeutic potential of doxorubicin (DOX) is limited by cardiotoxicity. Rubicon is an inhibitory interacting partner of autophagy protein UVRAG. Currently, the role of Rubicon in DOX-induced cardiotoxicity is unknown. In this study, we test the hypothesis that loss of Rubicon attenuates DOX-induced cardiotoxicity. MethodsA mouse model of acute DOX-induced cardiotoxicity was established by a single intraperitoneal injection of DOX at a dose of 20 mg/kg. Rubicon expression was detected by Western blot. Cardiac damage was determined by measuring activities of lactate dehydrogenase and myocardial muscle creatine kinase in the serum, cytoplasmic vacuolization, collagen deposition, ROS levels, ATP content and mitochondrial damage in the heart. Cardiac morphometry and function were assessed by echocardiography. Markers for autophagy, mitophagy and mitochondrial dynamics were evaluated by Western blot and real time reverse transcription polymerase chain reaction. ResultsRubicon expression was reduced in the heart 16 h after DOX treatment. DOX induced accumulation of cytoplasmic vacuolization and collagen, increased serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, enhanced ROS levels, reduced ATP content, pronounced mitochondrial damage and greater left ventricular wall thickness in wild type mice, which were mitigated by Rubicon deficiency. Mechanistically, loss of Rubicon improved DOX-induced impairment of autophagic flux, Parkin-mediated mitophagy and mitochondrial fission and fusion in the heart. ConclusionsLoss of Rubicon ameliorates DOX-induced cardiotoxicity through enhancement of mitochondrial quality by improving autophagic flux, mitophagy and mitochondrial dynamics. Rubicon is a potential molecular target for prevention and therapy of DOX cardiotoxicity.

Reduced Estimated GFR and Cardiac Remodeling: A Population-Based Autopsy Study

Evidence suggests that cardiac remodeling, including left ventricular hypertrophy and myocardial fibrosis, develops with progression of kidney disease. Few studies have examined cardiac pathology across a range of estimated glomerular filtration rates (eGFRs), which was the objective of this investigation. Population-based cross-sectional study of deceased patients undergoing autopsy. 334 of 694 consecutive deceased patients undergoing autopsy with available cardiac tissue, with a prior health examination within 6 years and without a prior diagnosis of heart disease. eGFR. The thickness of the left ventricular wall, sizes of cardiac cells, and percentages of fibrosis, estimated from pathology examination of autopsy samples. Generalized estimating equations. Lower eGFRs were associated with greater left ventricular wall thickness. Deceased patients with eGFRs≥60, 45 to 59, 30 to 44, and<30mL/min/1.73m2 had left ventricular wall thicknesses of 9.1, 9.5, 9.8, and 10.3mm, respectively (P for trend<0.05). Lower eGFRs were also significantly associated with greater mean values of cardiac cell size in the left ventricular wall after adjusting for confounders: 15.3, 16.1, 16.4, and 17.4μm for eGFRs≥60, 45 to 59, 30 to 44, and<30mL/min/1.73m2 (P for trend<0.01). Patients with lower eGFRs had significantly higher multivariable-adjusted geometric mean values for fibrosis percentage in the left ventricular wall: 3.22%, 4.33%, 3.83%, and 6.14% for eGFRs≥60, 45 to 59, 30 to 44, and<30mL/min/1.73m2 (P for trend<0.001). The negative association of eGFR with multivariable-adjusted mean values of cardiac cell width was stronger among patients with than those without anemia. Cross-sectional study with a high proportion of elderly patients, no available information for severity or duration of hypertension and other cardiovascular risk factors, no information for medication use. These findings suggest that reduced eGFR is associated with cardiac hypertrophy and fibrosis of the left ventricle, cardiac cell enlargement, and cardiac fibrosis.

The Burden of Early Phenotypes and the Influence of Wall Thickness in Hypertrophic Cardiomyopathy Mutation Carriers

Sarcomere mutations and left ventricular (LV) hypertrophy (LVH) are cardinal features of hypertrophic cardiomyopathy (HCM). However, little is known about the full spectrum of phenotypic manifestations or how LVH influences disease expression. (1) To characterize and assess phenotypic burden in sarcomere mutation carriers (genotype positive [G+]) and (2) to investigate the correlation between LV wall thickness (LVWT) and other disease features in mutation carriers. This investigation was a cross-sectional, multicenter observational study in the setting of the HCMNet network of HCM clinical centers. Mutation carriers with LVH (G+/LVH+), mutation carriers without LVH (G+/LVH-), and healthy related control individuals (G-/LVH-) were enrolled through HCMNet sites. A total of 193 participants were enrolled and underwent study procedures. Participants were enrolled between April 9, 2010, and January 30, 2012. Study analysis was performed between June 2015 and May 2016. The primary stratifying variables were the presence of a sarcomere mutation and measures of LVWT. Variables from standardized exercise testing, echocardiography, cardiac magnetic resonance imaging, serum biomarker measurement, and electrocardiography were compared across study cohorts. Analyses were performed in 178 participants, including 81 G+/LVH+ (mean [SD] age at baseline, 27 [14] years), 55 G+/LVH- (20 [10] years), and 42 G-/LVH- (18 [8] years). All mutation carriers had smaller LV cavity, higher ratio of LVWT to diastolic diameter, and higher echocardiographic LV ejection fraction than controls. A phenotypic burden score was evaluated as the cumulative number of 7 traits (changes on electrocardiography; decreased LV systolic, diastolic diameter, or septal E' velocity; higher ratio of LVWT to diastolic diameter; serum troponin level; and natriuretic peptide level) in each individual. The mean (SE) phenotypic burden was 4.9 (0.2) phenotypes per individual in G+/LVH+, 2.4 (0.2) in G+/LVH-, and 1.3 (0.2) in controls (P < .001). Classification and regression tree analysis identified an LV end-diastolic dimension z score less than -1.85 or the combination of an LV end-diastolic dimension z score of -1.85 or higher and a septal E' velocity z score less than -0.52 as having 74% accuracy in discriminating G+/LVH- participants from controls. In mutation carriers, clinical variables demonstrated a continuous correlation with LVWT, generally without a clear cutoff signifying pathologic transition. G+/LVH- individuals demonstrated altered cardiac dimensions and function and a higher burden of early phenotypes than healthy G- controls. Two methods discriminated phenotypic subgroups, namely, a sum across 7 traits and a regression tree-based rule that identifies constellations of distinguishing factors. Greater LVWT is associated with more prominent cardiac abnormalities in a continuous, although not always linear, manner. A single value of LVWT could not dichotomize the presence or absence of disease.

Left Ventricular Structure and Function in Transthyretin-Related Versus Light-Chain Cardiac Amyloidosis

Immunoglobulin amyloid light-chain (AL)-related cardiac amyloidosis (CA) has a worse prognosis than either wild-type (ATTRwt) or mutant (ATTRm) transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in AL amyloidosis but not in TTR amyloidosis and might give insight into this difference. We assessed cardiac structure and function and outcome in a large population of patients with CA and compared findings in TTR and AL-related disease. We analyzed 172 patients with CA (AL amyloidosis, n=80; ATTRm, n=36; ATTRwt, n=56) by standard echocardiography and 2-dimensional speckle-tracking imaging-derived left ventricular (LV) longitudinal (LS), radial, and circumferential strains. Despite a preserved LV ejection fraction (55±12%), LS was severely impaired in CA. Standard measures of LV function and speckle-tracking imaging worsened as wall thickness increased, whereas apical LS was preserved regardless of the pathogenesis of CA and the degree of wall thickening. Compared with ATTRm and AL amyloidosis, ATTRwt was characterized by greater LV wall thickness and lower ejection fraction. LS was more depressed in both ATTRwt and AL amyloidosis (-11±3% and -12±4%, respectively, P=0.54) than in ATTRm (-15±4%, P<0.01 versus AL amyloidosis and ATTRwt). TTR-related causes were favorable predictors of survival, whereas LS and advanced New York Heart Association class were negative predictors. In patients with CA, worsening LV function correlated with increasing wall thickness regardless of pathogenesis. Patients with ATTRwt had a statistically greater wall thickness but lesser mortality than those with AL amyloidosis, despite very similar degrees of LS impairment. This paradox suggests an additional mechanism for LV dysfunction in AL amyloidosis, such as previously demonstrated light-chain toxicity.

Relationship of Delayed Enhancement by Magnetic Resonance to Myocardial Perfusion by Positron Emission Tomography in Hypertrophic Cardiomyopathy

Presence of delayed enhancement (DE) on cardiac magnetic resonance (CMR) is associated with worse clinical outcomes in hypertrophic cardiomyopathy. We investigated the relationship between DE on CMR and myocardial ischemia in hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy patients (n=47) underwent CMR for assessment of DE and vasodilator stress ammonia positron emission tomography to quantify myocardial blood flow and coronary flow reserve. The summed difference score for regional myocardial perfusion was also assessed. Patients in the DE group (n=35) had greater left ventricular wall thickness (2.09±0.44 versus 1.78±0.34 cm; P=0.03). Stress myocardial blood flow (2.25±0.46 versus 1.78±0.43 mL/min per gram; P=0.01) and coronary flow reserve (2.78±0.32 versus 2.01±0.52; P<0.001) were significantly lower in DE-positive patients. Summed difference score (7.3±6.6 versus 0.9±1.4; P<0.0001) was significantly higher in patients with DE. A coronary flow reserve <2.00 was seen in 18 patients (51%) with DE but in none of the DE-negative patients (P<0.0001). CMR and positron emission tomography showed visually concordant DE and regional myocardial perfusion abnormalities in 31 patients and absence of DE and perfusion defects in 9 patients. Four DE-positive patients demonstrated normal regional myocardial perfusion, and 3 DE-negative patients had (apical) regional myocardial perfusion abnormalities. We found a close relationship between DE by CMR and microvascular function in most of the patients studied. However, a small proportion of patients had DE in the absence of perfusion abnormalities, suggesting that microvascular dysfunction and ischemia are not the sole causes of DE in hypertrophic cardiomyopathy patients.

Enhanced resistance to permeability transition in interfibrillar cardiac mitochondria in dogs: effects of aging and long-term aldosterone infusion

Functional differences between subsarcolemmal and interfibrillar cardiac mitochondria (SSM and IFM) have been observed with aging and pathological conditions in rodents. Results are contradictory, and there is little information from large animal models. We assessed the respiratory function and resistance to mitochondrial permeability transition (MPT) in SSM and IFM from healthy young (1 yr) and old (8 yr) female beagles and in old beagles with hypertension and left ventricular (LV) wall thickening induced by 16 wk of aldosterone infusion. MPT was assessed in SSM and IFM by Ca(2+) retention and swelling. Healthy young and old beagles had similar mitochondrial structure, respiratory function, and Ca(2+)-induced MPT within SSM and IFM subpopulations. On the other hand, oxidative capacity and resistance to Ca(2+)-induced MPT were significantly greater in IFM compared with SSM in all groups. Old beagles treated with aldosterone had greater LV wall thickness and worse diastolic filling but normal LV chamber volume and systolic function. Treatment with aldosterone did not alter mitochondrial respiratory function but accelerated Ca(2+)-induced MPT in SSM, but not IFM, compared with healthy old and young beagles. In conclusion, in a large animal model, oxidative capacity and resistance to MPT were greater in IFM than in SSM. Furthermore, aldosterone infusion increased susceptibility to MPT in SSM, but not IFM. Together this suggests that SSM are less resilient to acute stress than IFM in the healthy heart and are more susceptible to the development of pathology with chronic stress.

The relationship between renal impairment and left ventricular structure, function, and ventricular–arterial interaction in hypertension

Our objective was to define the relationship between renal dysfunction--both albuminuria and reduced estimated glomerular filtration rate (eGFR)--and cardiac structure and diastolic dysfunction among patients with chronic hypertension. Both albuminuria and eGFR were measured in 540 asymptomatic patients with hypertension and diastolic dysfunction assessed by reduced early mitral annular relaxation velocity (E'). The majority of patients were white, mean age was 60 ± 10 years, mean SBP was 149 ± 18 mmHg, and there was a low prevalence comorbid conditions. Albuminuria was undetectable in 148 (27%), within the normal to low range [urine albumin-to-creatinine ratio (UACR) 1-25 mg/g for men, 1-17 mg/g for women] in 292 (54%), and high or very high (UACR >25 mg/g for men, >17 mg/g for women) in 100 (19%). Estimated GFR was 60 ml/min per 1.73 m² or less in 75 (14%), 61-90 ml/min per 1.73 m² in 244 (45%), and more than 90 ml/min per 1.73 m² in 221 (41%). Albuminuria, even within the normal range, was associated with greater left ventricular wall thickness (P = 0.01), higher relative wall thickness (P = 0.004), worse diastolic function reflected in lower E' (P = 0.01), greater arterial and left ventricular end-systolic stiffness (P < 0.0001 and P = 0.003, respectively), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) level (P = 0.0025), even after adjustment for differences in baseline characteristics. In contrast, no independent relationship was observed between eGFR and parameters of cardiac structure or function. Among asymptomatic hypertensive patients with evidence of diastolic dysfunction, the presence of albuminuria, even within the normal range, is associated with greater concentric remodeling, greater left ventricular end-systolic stiffness, and worse diastolic function.

Ethnic Differences in Physiological Cardiac Adaptation to Intense Physical Exercise in Highly Trained Female Athletes

Ethnicity is an important determinant of cardiovascular adaptation in athletes. Studies in black male athletes reveal a higher prevalence of electric repolarization and left ventricular hypertrophy than observed in white males; these frequently overlap with those observed in cardiomyopathy and have important implications in the preparticipation cardiac screening era. There are no reports on cardiac adaptation in highly trained black females, who comprise an increasing population of elite competitors. Between 2004 and 2009, 240 nationally ranked black female athletes (mean age 21+/-4.6 years old) underwent 12-lead ECG and 2-dimensional echocardiography. The results were compared with 200 white female athletes of similar age and size participating in similar sports. Black athletes demonstrated greater left ventricular wall thickness (9.2+/-1.2 versus 8.6+/-1.2 mm, P<0.001) and left ventricular mass (187.2+/-42 versus 172.3+/-42 g, P=0.008) than white athletes. Eight black athletes (3%) exhibited a left ventricular wall thickness >11 mm (12 to 13 mm) compared with none of the white athletes. All athletes revealed normal indices of systolic and diastolic function. Black athletes exhibited a higher prevalence of T-wave inversions (14% versus 2%, P<0.001) and ST-segment elevation (11% versus 1%, P<0.001) than white athletes. Deep T-wave inversions (-0.2 mV) were observed only in black athletes and were confined to the anterior leads (V(1) through V(3)). Systematic physical exercise in black female athletes is associated with greater left ventricular hypertrophy and higher prevalence of repolarization changes than in white female athletes of similar age and size participating in identical sporting disciplines. However, a maximal left ventricular wall thickness >13 mm or deep T-wave inversions in the inferior and lateral leads are rare and warrant further investigation.

Concentric left ventricular morphology in aerobically trained kayak canoeists

The aim of the present study was to test the hypothesis that upper body aerobically trained athletes (kayak canoeists) would have greater left ventricular wall thickness, but similar left ventricular diastolic chamber dimensions, compared with recreationally active and sedentary men. Ultrasound echocardiography was used to determine cardiac structure and function in highly trained kayak canoeists (n = 10), moderately active (n = 10) and sedentary men (n = 10). The septal and posterior left ventricular walls were ∼0.2 cm thicker in kayak canoeists (P < 0.05), and left ventricular mass was 51% and 32% greater (P < 0.05) in canoeists than in the sedentary and moderately trained participants, respectively. There were no differences in left ventricular chamber dimension, suggesting that the kayak canoeists had a concentric pattern of left ventricular adaptation to aerobic upper body training. Scaling the data to body composition indices had no effect on the outcome of the statistical analysis. There were no differences in resting Doppler left ventricular diastolic or systolic function among the groups. Ejection fraction was lower in the kayak canoeists, but the magnitude of the difference was within the normal variability for this measurement. Thus aerobically upper body trained athletes demonstrated a concentric pattern of cardiac enlargement, but resting left ventricle function was not different between athletes, moderately active and sedentary individuals.

Echocardiographic parameters in 14 healthy English Bull Terriers.

To determine the range of various cardiac parameters using echocardiography in apparently normal, healthy English Bull Terriers. Fourteen English Bull Terriers were selected for study. Cardiac auscultation of the parents of these dogs was normal. Echocardiographic examination of one parent of each animal showed: no mitral or aortic valve abnormalities; no myocardial lesions; no two dimensional evidence of fixed or dynamic left ventricular outflow tract obstruction; and no systolic aortic or left ventricular outflow tract turbulence on colour flow Doppler examination. The 14 selected dogs did not have arrhythmias or murmurs, and on echocardiographic examination had similar findings to their parents. Systolic blood pressure was measured in all dogs and they had no clinical evidence of Bull Terrier polycystic kidney disease or Bull Terrier hereditary nephritis. All dogs were auscultated and subjected to a sequential global echocardiographic assessment of the heart, including two dimensional long and short axis, and colour flow Doppler interrogation of the mitral and aortic valves. Dimensional measurements, including those from the left atrium, aortic annulus and left ventricle, were taken from a right parasternal window, and derived values such as fractional shortening, stroke volume and left atrial to aortic annulus ratio were calculated. Peak systolic aortic velocity was measured from the left parasternal window using two dimensional-guided pulsed wave Doppler with angle correction. Systolic blood pressure was measured using a Doppler monitor. The absence of Bull Terrier polycystic kidney disease was determined using renal ultrasonography, and of Bull Terrier hereditary nephritis using urinary protein to creatinine ratio. These 14 dogs had greater left ventricular wall thickness and smaller aortic root diameters than those reported as normal for other breeds of comparable body size. Left atrial dimensions were also larger, however this may have been due to the "maximising" method of measurement. These apparently normal English Bull Terriers also had higher aortic velocities than those reported for other breeds, possibly due to a smaller aortic root diameter or other anatomic substrate of the left ventricular outflow tract, lower systemic vascular resistance, or breed-specific "normal" left ventricular hypertrophy. While these dogs were selected to be as close to normal as possible, the breed may have a particular anatomy that produces abnormal left ventricular echocardiographic parameters. These echocardiographic parameters may be used to diagnose left ventricular outflow tract obstruction and left ventricular hypertrophy, and inaccurate diagnoses may result if breed-specific values are not used.

Maternally transmitted susceptibility to non–insulin-dependent diabetes mellitus and left ventricular hypertrophy

OBJECTIVESWe studied the association of diabetes transmission with left ventricular hypertrophy (LVH) in patients with non–insulin-dependent diabetes mellitus (NIDDM).BACKGROUNDIt is suggested that NIDDM has a strong genetic basis and that maternally transmitted NIDDM is associated with mitochondrial deoxyribonucleic acid (DNA) mutations. However, genetic factors for LVH in NIDDM are unknown.METHODSWe investigated the family history of diabetes and the prevalence of LVH using electrocardiography in 834 patients with NIDDM, of whom 199 also underwent echocardiography.RESULTSOf the 834 patients, 121 had diabetic mothers, 122 had diabetic fathers and 30 had both. The LVH criterion of SV1+ RV5or RV6>35 mm was met in 148 patients. The percentage of patients having diabetic mothers was higher in those with LVH criterion (29%) than without it (16%) (p < 0.001), but the percentage of patients having diabetic fathers was similar in those with LVH (18%) and without it (18%). Compared with the 683 patients with nondiabetic mothers, the 151 patients with diabetic mothers were younger and had earlier onset of diabetes. The percentage of patients having diabetic siblings was also higher in those with diabetic mothers (31%) than in those with nondiabetic mothers (18%) (p < 0.001). On electrocardiograms, the prevalence of LVH was higher in patients with diabetic mothers (28%) than in those with nondiabetic mothers (15%) (p < 0.001). Echocardiograms showed that patients with diabetic mothers had greater left ventricular wall thickness and mass than those with nondiabetic mothers. In multivariate analysis, the family history of diabetes in mothers was an independent factor to LVH, but the family history of diabetes in fathers was not.CONCLUSIONSMaternal transmission of diabetes was associated with LVH in patients with NIDDM. Some genetic factors of diabetes, such as mitochondrial DNA abnormalities, may contribute to the development of LVH in maternally transmitted NIDDM.

Do echocardiographic changes explain the age-associated increase in exercise-induced supraventricular arrhythmias?

Although exercise-induced supraventricular arrhythmias (EISVA) increase with advancing age, it is unclear whether age-associated changes in cardiac structure or function play a major role in this increase. To address this question, we examined the relationship between M-mode echocardiographic variables and EISVA occurring during maximal treadmill exercise in 366 healthy volunteers aged 20 to 90 years from the Baltimore Longitudinal Study of Aging. Simple (i.e., isolated) EISVA were detected in 69 subjects (19%), and complex EISVA (i.e., comprising > 10% of beats in any minute or occurring in runs) in another 29 subjects (8%). Univariate predictors of any EISVA, whether simple or complex, were older age (p < 0.0001), male gender (p < 0.05), greater left atrial size (p < 0.01), left ventricular mass index (p < 0.0001), interventricular septal thickness (p < 0.001), isovolumic relaxation time (p < 0.01), atrial filling fraction (p < 0.01), reduced mitral E-F closure slope (p < 0.001), peak E velocity (p < 0.02), and peak E/A ratio (p < 0.0001). Lesser exercise duration (p < 0.01), lower maximal heart rate (p < 0.0001), and higher peak systolic and diastolic blood pressures (p < 0.001) were also associated with EISVA. However, by multiple logistic regression analysis, age (p < 0.0001) was the only independent predictor of any EISVA. Univariate predictors of complex EISVA were greater age (p < 0.0001), and atrial filling fraction (p < 0.001), diastolic blood pressure (p < 0.05), lesser mitral E-F slope (p < 0.004), exercise duration (p < 0.005) and maximal heart rate (p < 0.01). However, only age (p < 0.0001) independently predicted complex EISVA. Thus, in healthy volunteers undergoing maximal treadmill exercise. EISVA are associated with greater left ventricular wall thickness, reduced early diastolic performance, diminished exercise capacity and elevated exercise blood pressure. However, none of these variables are independent predictors of EISVA over and above the powerful effect of age.