Eccentric Left Ventricular Remodeling Research Articles

Structural and functional abnormalities of left-sided cardiac chambers in Barlow's disease without significant mitral regurgitation.

To explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities in patients with Barlow's disease (BD) without significant mitral regurgitation (MR) and to investigate whether these abnormalities may predict MR progression. Consecutive patients with BD were retrospectively identified from two tertiary centers; those with MR graded from trivial to mild-to-moderate were selected and matched with healthy controls in a 1:1 ratio. Conventional and speckle-tracking echocardiographic data were collected. The development of moderate-to-severe or greater MR was evaluated on follow-up echocardiograms.Patients with BD (n=231) showed increased LV dimensions and indexed LV mass (LVMi) in comparison to controls (p<0.001); LV remodeling worsened with higher MR severity and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Moreover, BD patients had larger LA volumes and more impaired LA reservoir strain versus controls (p<0.001), while LV strain was similar between the two groups. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodeling markers (LV dimensions, LVMi and LA volume), and BD as independent correlate of LA strain.MR progression was observed in 51 BD subjects (out of 170 patients with available follow-up). On Cox regression analysis, age, eLVH, mild-to-moderate MR and mitral annular disjunction (MAD) emerged as independent predictors of MR progression. BD patients without significant MR show early LV and LA remodeling, together with reduced LA strain. MR progression was associated with eccentric LV remodeling, MAD, and MR severity.

Role of biomarkers of collagen metabolism and systemic inflammation in myocardial remodeling in patients with stable chronic coronary artery disease and obstructive sleep apnea

Aim. To study the relationship of biomarkers of collagen metabolism and systemic inflammation with left ventricular (LV) remodeling in patients with stable coronary artery disease (CAD) and obstructive sleep apnea (OSA).Material and methods. The study included 195 patients with stable CAD, of which 63 without OSA and 132 patients with combination of CAD and OSA. The mean age of patients was 63,4±3,7 years. Biomarkers of collagen metabolism and systemic inflammation were assessed by determining the concentration of matrix metalloproteinase (MMP)-9, tissue inhibitor of matrix metalloproteinase-1, monocyte chemoattractant protein-1 (MCP-1) and calculating the neutrophil-to-lymphocyte (NLR) and platelet-tolymphocyte ratio (PLR). Echocardiography was performed according to a standard protocol.Results. There were no significant differences in systemic inflammation parameters (MCP-1, NLR, PLR) between the group of patients with CAD and CAD with mild OSA and a significantly higher level of MCP-1, NLR, PLR in more severe OSA. In patients with CAD and severe OSA, the eccentric LV remodeling was diagnosed in 75% of individuals, while the concentric type was diagnosed in only 25%.Conclusion. In patients with stable CAD, the more severe the OSA, the more pronounced systemic inflammation (MCP-1, NLR, PLR), and there are higher proportion of eccentric LV hypertrophy, which may be associated with an imbalance of fibrosis markers (high concentration of MMP-9 with an almost unchanged level of tissue inhibitor of MMP-1).

Ventricular stiffening and chamber contracture in heart failure with higher ejection fraction.

Ancillary analyses from clinical trials have suggested reduced efficacy for neurohormonal antagonists among patients with heart failure and preserved ejection fraction (HFpEF) and higher ranges of ejection fraction (EF). A total of 621 patients with HFpEF were grouped into those with low-normal left ventricular EF (LVEF) (HFpEF<65% , n = 319, 50% ≤ LVEF <65%) or HFpEF≥65% (n = 302, LVEF ≥65%), and compared with 149 age-matched controls undergoing comprehensive echocardiography and invasive cardiopulmonary exercise testing. A sensitivity analysis was performed in a second non-invasive community-based cohort of patients with HFpEF (n = 244) and healthy controls without cardiovascular disease (n = 617). Patients with HFpEF≥65% had smaller left ventricular (LV) end-diastolic volume than HFpEF<65% , but LV systolic function assessed by preload recruitable stroke work and stroke work/end-diastolic volume was similarly impaired. Patients with HFpEF≥65% displayed an end-diastolic pressure-volume relationship (EDPVR) that was shifted leftward, with increased LV diastolic stiffness constant β, in both invasive and community-based cohorts. Cardiac filling pressures and pulmonary artery pressures at rest and during exercise were similarly abnormal in all EF subgroups. While patients HFpEF≥57% displayed leftward shifted EDPVR, those with HFpEF<57% had a rightward shifted EDPVR more typical of heart failure with reduced EF. Most pathophysiologic differences in patients with HFpEF and higher EF are related to smaller heart size, increased LV diastolic stiffness, and leftward shift in the EDPVR. These findings may help to explain the absence of efficacy for neurohormonal antagonists in this group and raise a new hypothesis, that interventions to stimulate eccentric LV remodelling and enhance diastolic capacitance may be beneficial for patients with HFpEF and EF in the higher range.

Extent of Left Ventricular Mass Regression and Impact of Global Left Ventricular Afterload on Cardiac Events and Mortality after Aortic Valve Replacement.

Patient-prosthesis mismatch (PPM) causes a high transvalvular pressure gradient and residual left ventricular (LV) hypertrophy, consequently influencing long-term results. This study aimed to find the relationships between hemodynamic parameters and LV mass regression and determine the risk predictors of major adverse cardiovascular and cerebral events (MACCE) after aortic valve replacement (AVR) for aortic stenosis. Methods and Results: Preoperative and postoperative Doppler echocardiography data were evaluated for 120 patients after AVR. The patients' mean age was 67.7 years; 55% of the patients were male. Forty-four (37%) patients suffered from MACCE during a mean follow-up period of 3.6 ± 2 years. The following hemodynamic parameters at follow-up were associated with lower relative indexed LV mass (LVMI) regression: lower postoperative indexed effective orifice area, greater mean transvalvular pressure gradient (MPG), greater stroke work loss (SWL), and concentric or eccentric LV remodeling mode. The following hemodynamic parameters at follow-up were associated with a higher risk of MACCE: higher valvuloarterial impedance (ZVA), greater SWL, greater MPG, greater relative wall thickness, greater LVMI, and hypertrophic LV remodeling mode. Lower relative LVMI regression was associated with a higher risk of MACCE (hazard ratio, 1.01: 95% confidence interval, 1.003-1.03). The corresponding cutoff of relative LVMI regression was -14%. Conclusions: Changes in hemodynamic parameters were independently associated with relative LVMI regression. Impaired reverse remodeling and persistent residual LV hypertrophy were independent risk predictors of MACCE. An LVMI regression lower than 14% indicated higher MACCE. A postoperative ZVA greater than 3.5 mmHg/mL/m2 was an independent risk predictor of cardiac events and mortality after AVR. Preventive strategies should be used at the time of the operation to avoid PPM.

Гендерні та вікові особливості ремоделювання серця у хворих із постінфарктним кардіосклерозом, цукровим діабетом 2-го типу та ожирінням

У статті було визначено гендерні та вікові особливості ремоделювання серця у хворих із постінфарктним кардіосклерозом, цукровим діабетом (ЦД) 2-го типу й ожирінням.Із цією метою проведено обстеження 295 хворих із постінфарктним кардіосклерозом. Гендерні та вікові особливості ремоделювання серця у 215 хворих із постінфарктним кардіосклерозом, цукровим діабетом 2-го типу та ожирінням порівнювали з такими у хворих, які не мали діабету й ожиріння (група порівняння (n = 80)). Усі хворі з постінфарктним кардіосклерозом були розподілені на групи залежно від наявності ЦД 2-го типу (перша група (n = 68)), ожиріння (друга група (n = 76)) та їх поєднаного перебігу (третя група (n = 71)). Усі групи були порівнянні за віком (64,38 ± 1,08; 64,87 ± 1,98; 65,13 ± 1,43 та 63,47 ± 1,28 року відповідно). Верифікацію діагнозу проводили на підставі чинних критеріїв. Усім хворим проводили загальноклінічні та інструментальні обстеження. Ехокардіографічні дослідження проводили за стандартною методикою Х. Фейгенбаума на ультразвуковому апараті RADMIR (Ultima PRO 30) (Харків, Україна).Гендерний аналіз показав вірогідне збільшення розмірів лівого шлуночка та лівого передсердя на тлі більш вираженого зниження систолічної функції у чоловіків із постінфарктним кардіосклерозом, ЦД 2-го типу та ожирінням порівняно з жінками незалежно від віку. У хворих похилого віку спостерігалися такі самі зміни, як у хворих середнього віку. У всіх обстежених хворих виявлялося порушення геометричної адаптації, із них концентричний тип ремоделювання був переважно в осіб жіночої статі, в обстежених чоловіків частіше траплялося ексцентричне ремоделювання лівого шлуночка.Таким чином, у жінок валідними факторами, що визначають тяжкість ураження міокарда лівого шлуночка і перебігу хронічної серцевої недостатності на тлі перенесеного інфаркту міокарда, є ЦД 2-го типу, надлишкова маса тіла й перевага сприятливого концентричного типу ремоделювання лівого шлуночка зі збереженою його систолічною функцією. Тоді як у чоловіків ремоделювання міокарда має менш сприятливий перебіг зі збільшенням розмірів лівого шлуночка та лівого передсердя на тлі більш вираженого зниження систолічної функції.

Effect of concomitant aortic regurgitation on early hypoattenuated leaflet thickening after transcatheter aortic valve replacement in patients with symptomatic severe aortic stenosis

Identification of hypoattenuated leaflet thickening (HALT) and subacute leaflet thrombosis has become widely recognized. Patients with anatomical changes associated with moderate or greater aortic regurgitation (larger sinus of Valsalva and eccentric left ventricular remodeling) appear to have less HALT early postprocedure compared with those without. Further research on the risk factors including anatomical and hemodynamic variables should further our knowledge of these entities so we can better manage patient both pre and post TAVR.

Abstract 14952: Hemodynamic Comparison of Left Ventricular Function in Pressure Overload- versus Volume Overload-Induced Heart Failure Models by Invasive Pressure-Volume Analysis

Introduction: Both sustained left ventricular (LV) pressure overload (PO) and volume overload (VO) induces LV remodeling and eventually development of heart failure (HF). Using rat models, the present study aimed to provide a detailed comparison of distinct aspects of LV function in PO- and VO-induced HF. Methods: PO and VO was induced by transverse aortic constriction (TAC, n=12) and aortocaval shunt (AV-shunt, n=12) creation respectively. Controls underwent corresponding sham operations (n=11). LV remodeling was characterized by echocardiography, histology, qRT PCR, and western blot. LV function was assessed by invasive pressure-volume (P-V) analysis. Results: Both sustained PO and VO resulted in the development of HF, as evidenced by increased LV BNP mRNA expression, pulmonary edema, and characteristic symptoms. While the extent of LV hypertrophy was comparable between the HF models, PO induced concentric while VO evoked eccentric LV remodeling. P-V analysis revealed impaired systolic function in both HF models. Accordingly, decreased ejection fraction and impaired ventriculo-arterial coupling (calculated as the ratio of arterial elastance/LV contractility [VAC]: 0.38±0.05 vs. 1.30±0.13, ShamTAC vs. TAC and 0.52±0.08 vs. 1.17±0.13, ShamAV-Shunt vs. AV-shunt; p&lt;0.05) was detected in both HF models. However, in case of VO the severely reduced LV contractility (slope of end-systolic P-V relationship: 1.79±0.19 vs. 0.52±0.06, ShamAV-Shunt vs. AV-shunt, p&lt;0.05 and 2.14±0.28 vs. 2.03±0.21, ShamTAC vs. TAC p&gt;0.05) underpinned the contractility-afterload mismatch, while in case of PO the increased afterload (arterial elastance: 0.77±0.07 vs. 2.64±0.28, ShamTAC vs. TAC and 0.80±0.07 vs. 0.54±0.05, ShamAV-Shunt vs. AV-shunt; p&lt;0.05) was the main determinant. Furthermore, prolongation of active relaxation occurred to a greater extent in case of PO. In addition, increased myocardial stiffness was only observed in PO-induced HF. Conclusion: Systolic function was reduced in both HF models. However, different factors underpinned the impaired VAC in case of VO (reduced LV contractility) and PO (increased arterial elastance). Furthermore, although diastolic function deteriorated in both models, it occurred to a greater extent in case of PO.

NADPH oxidase-4 promotes eccentric cardiac hypertrophy in response to volume overload.

AimsChronic pressure or volume overload induce concentric vs. eccentric left ventricular (LV) remodelling, respectively. Previous studies suggest that distinct signalling pathways are involved in these responses. NADPH oxidase-4 (Nox4) is a reactive oxygen species-generating enzyme that can limit detrimental cardiac remodelling in response to pressure overload. This study aimed to assess its role in volume overload-induced remodelling.Methods and resultsWe compared the responses to creation of an aortocaval fistula (Shunt) to induce volume overload in Nox4-null mice (Nox4−/−) vs. wild-type (WT) littermates. Induction of Shunt resulted in a significant increase in cardiac Nox4 mRNA and protein levels in WT mice as compared to Sham controls. Nox4−/− mice developed less eccentric LV remodelling than WT mice (echocardiographic relative wall thickness: 0.30 vs. 0.27, P < 0.05), with less LV hypertrophy at organ level (increase in LV weight/tibia length ratio of 25% vs. 43%, P < 0.01) and cellular level (cardiomyocyte cross-sectional area: 323 µm2 vs. 379 μm2, P < 0.01). LV ejection fraction, foetal gene expression, interstitial fibrosis, myocardial capillary density, and levels of myocyte apoptosis after Shunt were similar in the two genotypes. Myocardial phospho-Akt levels were increased after induction of Shunt in WT mice, whereas levels decreased in Nox4−/− mice (+29% vs. −21%, P < 0.05), associated with a higher level of phosphorylation of the S6 ribosomal protein (S6) and the eIF4E-binding protein 1 (4E-BP1) in WT compared to Nox4−/− mice. We identified that Akt activation in cardiac cells is augmented by Nox4 via a Src kinase-dependent inactivation of protein phosphatase 2A.ConclusionEndogenous Nox4 is required for the full development of eccentric cardiac hypertrophy and remodelling during chronic volume overload. Nox4-dependent activation of Akt and its downstream targets S6 and 4E-BP1 may be involved in this effect.

Myocardial Adaptations to Competitive Swim Training

Swim training is performed in the prone or supine position and obligates water immersion, factors that may augment cardiac volume loading more than other endurance sports. At present, prospective data defining the cardiac responses to swim training are lacking. We therefore studied myocardial adaptations among competitive swimmers to establish a causal relationship between swim training and left ventricular (LV) remodeling. Collegiate swimmers were studied before and after a 90-d period of training intensification. Transthoracic echocardiography was used to examine LV structural and functional adaptations under resting conditions and during an acute LV afterload challenge generated by isometric handgrip testing (IHGT). A sedentary control population was identically studied with IHGT. In response to a discrete period of swim training intensification, athletes (n = 17, 47% female, 19 ± 0.4 yr old) experienced eccentric LV remodeling, characterized by proportionally more chamber dilation than wall thickening, with attendant enhancements of resting LV systolic (LV twist) and diastolic (early and late phase tissue velocities) function. Compared with baseline and controls, athletes posttraining demonstrated greater systolic twist impairment during IHGT. However, training-induced LV dilation coupled with gains in diastolic function offsets this acquired systolic susceptibility to acute afterload, resulting in the relative preservation of stroke volume during IHGT. Swim training, a sport characterized by unique cardiac loading conditions, stimulates eccentric LV remodeling with the concomitant augmentation of systolic twist and diastolic relaxation. This volume-mediated cardiac remodeling appears to result in greater systolic susceptibility to acute afterload challenge. Further work is required to establish how training-induced changes in function translate to human performance and whether these are accompanied by physiologic trade-offs with relevance to common forms of heart disease.

Relationship between Aortic Compliance and Impact of Cerebral Blood Flow Fluctuation to Dynamic Orthostatic Challenge in Endurance Athletes.

Aorta effectively buffers cardiac pulsatile fluctuation generated from the left ventricular (LV) which could be a mechanical force to high blood flow and low-resistance end-organs such as the brain. A dynamic orthostatic challenge may evoke substantial cardiac pulsatile fluctuation via the transient increases in venous return and stroke volume (SV). Particularly, this response may be greater in endurance-trained athletes (ET) who exhibit LV eccentric remodeling. The aim of this study was to determine the contribution of aortic compliance to the response of cerebral blood flow fluctuation to dynamic orthostatic challenge in ET and age-matched sedentary (SED) young healthy men. ET (n = 10) and SED (n = 10) underwent lower body negative pressure (LBNP) (−30 mmHg for 4 min) stimulation and release the pressure that initiates a rapid regain of limited venous return and consequent increase in SV. The recovery responses of central and middle cerebral arterial (MCA) hemodynamics from the release of LBNP (~15 s) were evaluated. SV (via Modeflow method) and pulsatile and systolic MCA (via transcranial Doppler) normalized by mean MCA velocity (MCAv) significantly increased after the cessation of LBNP in both groups. ET exhibited the higher ratio of SV to aortic pulse pressure (SV/AoPP), an index of aortic compliance, at the baseline compared with SED (P < 0.01). Following the LBNP release, SV was significantly increased in SED by 14 ± 7% (mean ± SD) and more in ET by 30 ± 15%; nevertheless, normalized pulsatile, systolic, and diastolic MCAv remained constant in both groups. These results might be attributed to the concomitant with the increase in aortic compliance assessed by SV/AoPP. Importantly, the increase in SV/AoPP following the LBNP release was greater in ET than in SED (P < 0.01), and significantly correlated with the baseline SV/AoPP (r = 0.636, P < 0.01). These results suggest that the aortic compliance in the endurance athletes is able to accommodate the additional SV and buffer the potential increase in pulsatility at end-organs such as the brain.

Strategy for Prevention of Left Ventricular Remodeling in Predialysis and Dialysis Patients.

Currently, left ventricular (LV) hypertrophy and dysfunction are considered the strongest predictors of cardiovascular mortality in chronic kidney disease (CKD) patients. We investigated the factors associated with elevated LV mass index (LVMI) using echocardiography and assessed the strategies used to treat CKD (stages 1-5D) patients. In study 1, we prospectively determined correlations among biochemical values, physical specimens, and LVMI using echocardiography in hemodialysis (HD) and peritoneal dialysis (PD) patients (stage 5D). In study 2, biochemical and physical values were collected over a period of more than 120 days prior to the initiation of dialysis in predialysis patients. LVMI was evaluated by echocardiography twice (at baseline and during follow-up at the initiation of the dialysis period). In study 3, physical, biochemical, and LVMI data were also retrospectively analyzed in 930 CKD (stages 1-5) patients. Results 1: In HD patients, LVMI values at 24 months were not significantly decreased compared with those at baseline. Systolic blood pressure (SBP) and hemoglobin (Hb) levels were identified as independent risk factors for LVMI after 24 months. In PD patients, LVMI values at 24 months were significantly decreased compared with those at baseline. Results 2: A lower LVMI at the initiation of dialysis and improved LVMI during the observation period were detected in the highest tertile of average Hb (10.4 g/dL). Results 3: In early CKD (stages 1-3) patients, LVMI, urinary protein, and Hb levels were independently associated with factors for progression to dialysis. In CKD (stages 1-5) patients, LVMI increased with decreasing renal function, and eccentric LV remodeling was increased. Levels of SBP and Hb were independent risk factors for LVMI. In the patients who showed worsening LVMI, the rates of change in SBP, proteinuria, and Hb were identified as independent risk factors for LVMI changes. Key Messages: It is important to treat hypertension and anemia to prevent LV remodeling not only during the dialysis stage but also from early CKD stages to initiation of dialysis in CKD patients. Our findings may offer potential therapeutic strategies for treating predialysis and dialysis patients.

Serum apolipoprotein B is inversely associated with eccentric left ventricular hypertrophy in peritoneal dialysis patients

The study aimed to examine the relationship of serum apolipoprotein B level with left ventricular (LV) structural and functional characteristics, in particular, LV remodeling parameters in peritoneal dialysis (PD) patients. A total of 182 patients with end-stage renal disease (ESRD) receiving PD were identified. Conventional echocardiography was performed for each patient, and echocardiographic characteristics were analyzed according to apo B quartile groups. Multivariate linear regression models were used to determine the associations between serum apo B and LV remodeling indices. A high serum apo B level was significantly related to the reduction in left atrium dimension (r=-0.20, P=0.011), LV dimensions (end-diastolic: r=-0.27, P=0.001; end-systolic: r=-0.24, P=0.003), peak velocities of early filling divided by peak velocities of atrial filling (r=-0.38, P<0.001), and LV volumetric dimension (end-diastolic: r=-0.27, P<0.001; end-systolic: r=-0.28, P<0.001). After adjustment for clinical confounding factors, the effect of serum apo B on LV eccentric remodeling modestly weakened but remained statistically significant (P=0.038), while other associations were not significant. In multivariate linear regression analysis, conventional lipid profiles were not significantly associated with LV eccentric remodeling, whereas serum apo B was an independent determinant of LV dilatation (β: -42.10, 95% CI -74.82 to -9.38, P=0.012). Serum apo B was significantly and inversely associated with LV dilatation, independently of conventional lipids and other CV risk factors in our ESRD patients undergoing PD. It suggested that low serum apo B level could be a powerful risk marker for eccentric left ventricular geometry remodeling and could be potentially used to risk-stratify PD patients.

P4929Femoral pulse wave velocity relates to eccentric left ventricular remodeling in masked hypertension: The African-PREDICT study

P4929Femoral pulse wave velocity relates to eccentric left ventricular remodeling in masked hypertension: The African-PREDICT study

Exercise training ameliorates matrix metalloproteinases 2 and 9 messenger RNA expression and mitigates adverse left ventricular remodeling in streptozotocin-induced diabetic rats.

The aim was to investigate whether exercise training (ExT) would ameliorate expression of key genes for myocardial morphostructure and mitigate adverse left ventricular (LV) remodeling in experimental type 1 diabetes (T1D). Male Wistar rats were divided into four groups: sedentary control (SC, n=9), trained control (TC, n=13), sedentary diabetic (SD, n=20), and trained diabetic (TD, n=17). T1D was induced by 40 mg/kg streptozotocin (single dose, i.v.). Training program consisted of 4-week treadmill running (60 min/day, 5 days/wk). Structure of the LV was evaluated using histomorphometric techniques. Gene expression changes of LV collagens I and III, metalloproteinases (MMPs) 2 and 9, and transforming growth factor-β1 were detected by reverse transcriptase quantitative polymerase chain reaction. Compared with SC, SD rats presented LV eccentric remodeling, myocyte hypertrophy, and fibrosis, whereas TD animals showed normal LV geometry and collagen content but thinner myocytes. Expression of collagens and type I/III collagen messenger RNA (mRNA) ratio were diminished in diabetic hearts compared with SC. MMP-2 gene was down-regulated in SD, whereas TD group showed decreased MMP-9 mRNA levels and MMP-2 expression comparable to that of SC rats. Attenuation of MMP-2 down-regulation and reduction in MMP-9 mRNA expression may constitute an underlying mechanism by which ExT counteracts progression of adverse LV remodeling in T1D.

Changes in Body Weight and Composition Are Associated With Changes in Left Ventricular Geometry and Function in the General Population: SHIP (Study of Health in Pomerania).

The different effects of total body weight (TBW), fat-free mass (FFM), and fat mass (FM) on left ventricular (LV) geometry and function are complex. We investigated the associations of changes over time in TBW, FM, and FFM with changes in LV geometry and function. We analyzed data from 1189 subjects (694 women), aged 44 to 86 years, from the baseline and the 5-year follow-up examination of the population-based SHIP (Study of Health in Pomerania). TBW was measured, and FFM and FM were calculated based on height-weight models derived from bioelectrical impedance studies. Echocardiographic measurements of LV geometry and function were performed according to the guidelines of the American Society of Echocardiography. Changes in body composition measures were associated with changes in LV geometry and function by multivariable-adjusted linear regression models. A 1-kg increase/decrease in TBW or FM was associated, respectively, with an increase/decrease of 0.89 g or 1.84 g in LV mass, whereas there was no such association on changes in FFM. Moreover, an increase in FM was associated with LV concentric remodeling and impairment of systolic and diastolic function parameters, whereas an increase in FFM was associated with LV eccentric remodeling and improved systolic and diastolic functional variables. Our findings indicate that changes in LV morphology and function depend on the type of body mass composition. Prospective data need to address whether specific changes in body composition over time may affect the risk for heart dysfunction more precisely than the change in TBW.

Aortic stenosis with abnormal eccentric left ventricular remodeling secondary to hypothyroidism in a Bourdeaux Mastiff

ABSTRACT: This paper describes a case of congenital aortic stenosis with eccentric left ventricular hypertrophy associated with hypothyroidism in a 1-year-old Bourdeaux Mastiff dog. The dog had ascites, apathy, alopecic and erythematous skin lesions in different parts of the body. A two-dimensional echocardiogram revealed aortic valve stenosis, with poststenotic dilation in the ascending aorta. The same exam showed eccentric hypertrophy and dilation of the left ventricle during systole and diastole. Aortic stenosis usually results in concentric left ventricular hypertrophy instead of eccentric hypertrophy; and therefore, this finding was very unusual. Hypothyroidism, which is uncommon in young dogs, may be incriminated as the cause of ventricular dilation, making this report even more interesting. Because hypothyroidism would only result in dilatation, the eccentric hypertrophy was attributed to pressure overload caused by aortic stenosis. Thus, cardiac alterations of this case represent a paradoxical association of both diseases.

Sex-Specific Effects of Adrenergic-Induced Left Ventricular Remodeling in Spontaneously Hypertensive Rats

ObjectiveThe aim of this work was to determine whether adrenergic-induced left ventricular (LV) dilation and eccentric remodeling in pressure-overload hypertrophy is sex specific. Methods and ResultsChronic β-adrenoreceptor activation was produced in male and female spontaneously hypertensive rats (SHRs) by means of daily administration of isoproterenol (ISO; 0.04 mg/kg daily) from 9 to 15 months of age. LV chamber dimensions were determined in vivo by means of echocardiography and ex vivo in isolated perfused heart preparations. The acute hemodynamic response to ISO, the degree of myocardial necrosis and apoptosis, and collagen distribution were also assessed. Female SHRs demonstrated inotropic and chronotropic responses to ISO similarly to male SHRs. Compared with control subjects (saline solution vehicle), following chronic ISO administration, LV end-diastolic diameter (mm) was increased in male (ISO 7.8 ± 0.3 vs control 6.6 ± 0.2; P < .001) but not in female (ISO 6.3 ± 0.2 vs control 6.2 ± 0.2; P = .23) SHRs. Similarly, compared with control, ISO administration increased the volume intercept of the LV end-diastolic pressure-volume relation (mL) in male (ISO 0.31 ± 0.02 vs control 0.22 ± 0.01; P < .0001) but not in female (ISO 0.17 ± 0.01 vs control 0.17 ± 0.01; P = 1.00) SHRs. Relative wall thickness was also decreased in male SHRs receiving ISO but not in female SHRs receiving ISO. Chronic ISO administration increased the percentage of area covered by interstitial collagen in male but not in female SHRs. Finally, chronic adrenergic stimulation failed to influence LV chamber or myocardial systolic function in either male or female SHRs. ConclusionsMale SHRs are more susceptible to adrenergic-induced LV dilation and eccentric LV remodeling than female SHRs. These effects are associated with increased collagen deposition. In pressure-overload hypertrophy, LV dilation and eccentric LV remodeling occur before LV dysfunction in male rats.

Light to Moderate Habitual Alcohol Consumption Is Associated with Subclinical Ventricular and Left Atrial Mechanical Dysfunction in an Asymptomatic Population: Dose-Response and Propensity Analysis

The effects of light to moderate alcohol consumption on cardiac mechanics remain poorly understood. The aim of this study was to investigate the dose-response relationship between alcohol consumption and left ventricular (LV) and left atrial (LA) function using myocardial deformation. In total 3,946 asymptomatic participants (mean age, 49.7±10.7years; 65% men) were consecutively studied using comprehensive echocardiography and two-dimensional speckle-tracking in a cross-sectional, retrospective manner. Global LV longitudinal and circumferential strain and LA strain were assessed and related to habitual alcohol consumption pattern (fewer than one, one to six, or more than six drinks per week) before and after propensity matching. With increasing weekly alcohol consumption, participants displayed greater LV eccentric remodeling, impaired diastolic function, and more attenuated global longitudinal strain, LA strain (adjusted coefficients, -1.07 [95% CI, -1.95 to -0.19] and -3.73 [95% CI, -5.36 to -2.11]), and early diastolic strain rates (adjusted coefficients, 0.07 [95% CI, 0.03-0.11] and 0.33 [95% CI, 0.24-0.42]) for one to six and more than six drinks per week, respectively (P<.05 for all) in a dose-response manner. Participants with recent alcohol abstinence displayed cardiac mechanics intermediate between those of nondrinkers and current drinkers. After propensity matching (n=1,140), participants currently consuming more than one drink per week continued to have significantly attenuated global longitudinal strain and all LA mechanics compared with those consuming fewer than one drink per week (P<.05 for all). Habitual alcohol consumption, even at light to moderate doses, is associated with both reduced LV and LA mechanics in a dose-dependent manner. Whether such observations are reversible or related to future atrial fibrillation deserves further study.

High-Output Heart Failure: A 15-Year Experience

BackgroundHigh-output heart failure (HF) is an unusual cause of cardiac failure that has not been well-characterized. ObjectivesThis study sought to characterize the etiologies, pathophysiology, clinical and hemodynamic characteristics, and outcomes of high-output HF in the modern era. MethodsWe performed a retrospective analysis of all consecutive patients referred to the Mayo Clinic catheterization laboratory for hemodynamic assessment between 2000 and 2014. Subjects with definite HF, as defined by the Framingham criteria, were compared to controls of similar age and sex. ResultsThe most common etiologies of high-output HF (n = 120) were obesity (31%), liver disease (23%), arteriovenous shunts (23%), lung disease (16%), and myeloproliferative disorders (8%). Compared with controls (n = 24), subjects with high-output HF displayed eccentric left ventricular remodeling, greater natriuretic peptide activation, higher filling pressures, pulmonary hypertension, and increased cardiac output, despite similar ejection fraction. Elevated cardiac output in high-output HF patients was related to both lower arterial afterload (decreased systemic vascular resistance) and higher metabolic rate. Mortality was increased in high-output HF as compared with controls (hazard ratio: 3.4; 95% confidence interval: 1.6 to 7.6). Hemodynamics and outcomes were poorest amongst patients with the lowest systemic vascular resistance. ConclusionsHigh-output HF is an important cause of clinical HF in the modern era that is related to excessive vasodilation, and most frequently caused by obesity, arteriovenous shunts, and liver disease. Given the high mortality and increasing prevalence of these comorbidities in Western countries, high-output HF must be considered in the differential diagnosis of patients presenting with dyspnea, congestion, and a normal ejection fraction.

The Multiple Mechanistic Faces of a Pure Volume Overload: Implications for Therapy

Mitral regurgitation and other conditions marked by a pure isolated volume overload (VO) of the heart result in a progressive form of eccentric left ventricular remodeling and dysfunction. As opposed to the more extensively studied pressure overload, there are no approved medical therapies because an understanding of the underlying pathological mechanisms at work in VO is lacking. Over the past 20 years, our laboratory has identified multiple key biological functions involved in the pathological remodeling in VO. Specifically, we have noted perturbed matrix homeostasis, detrimental adrenergic signaling, increased intracellular reactive oxygen species and an intense inflammatory response that implicates mast cells and their product chymase, which seems to cause extensive remodeling both inside and outside the cardiomyocyte. How these multiple pathways intersect over the course of VO and their response to various single and combined interventions are now the subject of intense investigation.