BackgroundTissue Doppler index E/è is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure (LVFP) and diastolic dysfunction (DD)/heart failure with preserved ejection fraction (HFpEF). Its diagnostic accuracy is not well studied.Methods and ResultsFrom the PubMed, Scopus, Embase, and Cochrane databases, we identified 24 studies reporting E/è and invasive LVFP in preserved EF (≥50%). In random‐effects models, E/è had poor to mediocre linear correlation with LVFP. Summary sensitivity and specificity (with 95% CIs) for the American Society of Echocardiography–recommended E/è cutoffs (lateral, mean, and septal, respectively) to identify elevated LVFP was estimated by using hierarchical summary receiver operating characteristic analysis. Summary sensitivity was 30% (9–48%), 37% (13–61%), and 24% (6–46%), and summary specificity was 92% (82–100%), 91% (80–99%), and 98% (92–100%). Positive likelihood ratio (LR+) was <5 for lateral and mean E/è. LR+ was slightly >10 for septal E/è obtained from 4 studies (cumulative sample size <220). For excluding elevated LVFP, summary sensitivity for E/è (lateral, mean, and septal, respectively) was 64% (38–86%), 36% (3–74%), and 50% (14–81%), while summary specificity was 73% (54–89%), 83% (49–100%), and 89% (66–100%). Because of data set limitations, meaningful inference for identifying HFpEF by using E/è could not be drawn. With the use of quality assessment tool for diagnostic accuracy studies (Quality Assessment of Diagnostic Accuracy Studies questionnaire), we found substantial risks of bias and/or applicability.ConclusionsThere is insufficient evidence to support that E/è can reliably estimate LVFP in preserved EF. The diagnostic accuracy of E/è to identify/exclude elevated LVFP and DD/HFpEF is limited and requires further validation in a well‐designed prospective clinical trial.

Objectives We assessed myocardial damage in patients with chronic isolated mitral regurgitation (MR) and LV ejection fraction (EF) > 60%. Background MR patients typically have decreased LVEF after mitral valve (MV) repair despite normal pre-operative LVEF. Methods 27 patients with isolated MR had LV biopsies taken at time of MV repair. Magnetic resonance imaging with tissue tagging was performed in 40 normal subjects and in MR patients pre- and 6 months post-MV repair. Results LVEF (66 ± 1 to 54 ± 2% p<0.0001) and LV end-diastolic volume index (108 ± 5 to 78 ± 5 ml/m2 p<0.0001) decreased, while LV end-systolic volume index (ESVI) was 60% above normal pre- and post-MV repair (p<0.05). LV circumferential and longitudinal strain rates decreased below normal post-MV repair (6.38 ± 0.30 vs. 5.11 ± 0.25 p=0.0009, and 7.51 ± 0.50 vs. 5.31 ± 0.30, %RR, p<0.0001), as LVES stress (σ)/LVESVI ratio was depressed at baseline and post-MV repair vs. normals (0.25 ± 0.02 and 0.28 ± 0.01 vs. 0.33 ± 0.02, p < 0.01). LV biopsies demonstrated cardiomyocyte myofibrillar degeneration vs. normals (p=0.0016). Immunostaining and immunoblotting demonstrated increased xanthine oxidase (XO) in MR vs. normals (p<0.05). Lipofuscin deposition was increased in cardiomyocytes of MR vs. normals (0.62 ± 0.04 vs. 0.33 ± 0.04, % area, p <0.01). Conclusions Decreased LV strain rates and LVES σ/ESVI post-MV repair indicate contractile dysfunction, despite pre-surgical LVEF > 60%. Increased oxidative stress could cause myofibrillar degeneration and lipofuscin accumulation resulting in LV contractile dysfunction in MR.

Background The volume overload of isolated mitral regurgitation (MR) in the dog results in left ventricular (LV) dilatation and interstitial collagen loss. To better understand the mechanism of collagen loss we performed a gene array and overlaid regulated genes into Ingenuity Pathway Analysis (IPA). Methods and Results Gene arrays from LV tissue were compared in 4 dogs prior to and 4 months after MR. Cine-magnetic resonance-derived LV end-diastolic volume increased 2-fold (p=0.005) and LV ejection fraction increased from 41 to 53% (p < 0.001). LV interstitial collagen decreased 40% (p<0.05) compared to controls and replacement collagen was in short strands and in disarray. IPA identified Marfan’s syndrome, aneurysm formation, LV dilatation, and myocardial infarction, all of which have extracellular matrix (ECM) protein defects and/or degradation. MMP-1 and -9 mRNA increased 5- (p=0.01) and 10-fold (0.003), while collagen I did not change and collagen III mRNA increased 1.5-fold (p=0.02). However, noncollagen genes important in ECM structure were significantly downregulated, including decorin, fibulin 1, and fibrillin 1. Decorin mRNA downregulation correlated with LV dilatation (r= 0.83 p<0.05). In addition, connective tissue growth factor and plasminogen activator inhibitor were downregulated, along with multiple genes in TGF-β signaling pathway, resulting decreased LV TGF-β1 activity (p=0.03). Conclusions LV collagen loss in isolated, compensated MR is chiefly due to post-translational processing and degradation. The downregulation of multiple noncollagen genes important in global ECM structure, coupled with decreased expression of multiple profibrotic factors, explain the failure to replace interstitial collagen in the MR heart.

Abstract-We have shown previously that patients with resistant hypertension and hyperaldosteronism have increased brain natriuretic peptide suggestive of increased intravascular volume. In the present study, we tested the hypothesis that hyperaldosteronism contributes to cardiac volume overload. Thirty-seven resistant hypertensive patients with hyperaldosteronism (urinary aldosterone Ն12 g/24 hours and plasma renin activity Յ1.0 ng/mL per hour) and 71 patients with normal aldosterone status were studied. Both groups had similar blood pressure and left ventricular mass, whereas left and right ventricular end-diastolic volumes measured by cardiac MRI were greater in high versus normal aldosterone subjects (PϽ0.05). Spironolactone treatment (19 patients in the high aldosterone group and 15 patients from the normal aldosterone group participated in the follow-up) resulted in a significant decrease in clinic systolic blood pressure, right and left ventricular end diastolic volumes, left atrial volume, left ventricular mass, and brain natriuretic peptide at 3 and 6 months of follow-up in patients with high aldosterone, whereas in those with normal aldosterone status, spironolactone decreased blood pressure and left ventricular mass without changes in ventricular or atrial volumes or plasma brain natriuretic peptide. Hyperaldosteronism causes intracardiac volume overload in patients with resistant hypertension in spite of conventional thiazide diuretic use. Mineralocorticoid receptor blockade induces rapid regression of left ventricular hypertrophy irrespective of aldosterone status. In subjects with high aldosterone, mineralocorticoid receptor blockade induces a prominent diuretic effect compared with a greater vasodilatory effect in subjects with normal aldosterone status. (Hypertension. 2010;55:1137-1142.)Key Words: resistant hypertension Ⅲ hyperaldosteronism Ⅲ cardiac volume Ⅲ cardiac hypertrophy A ldosterone excess is increasingly recognized as a common cause of hypertension. [1][2][3][4][5][6][7][8][9][10][11] Compared with patients with similar levels of hypertension, patients with hyperaldosteronism have greater left ventricular (LV) hypertrophy, worse diastolic function, and an increased rate of cardiovascular complications including myocardial infarction, stroke, and atrial fibrillation. [12][13][14][15] In such patients, echocardiographic/Doppler studies provide support for aldosterone-induced myocardial fibrosis and hypertrophy separate from changes in blood pressure (BP). 16 -19 A large body of experimental literature, including landmark studies by Brilla and Weber, 20 clearly demonstrates that aldosterone excess in the presence of high dietary salt intake induces LV hypertrophy and fibrosis. [21][22][23] These effects are attributable, at least in part, to aldosterone-induced urinary and fecal loss of Ca 2ϩ and Mg 2ϩ , with consequent hypocalcemia, hypomagnesia, and secondary hyperparathyroidism. This secondary increase in parathyroid hormone promotes intracellular Ca 2ϩ overloading in various tissues, ...