Chronic Left Ventricular Volume Research Articles

Differences in Left Ventricular Enlargement Secondary to Chronic Volume Loading Between English Springer Spaniels and Two Similar Sporting Breeds

IntroductionEnglish springer spaniels have larger, rounder ventricles than most other breeds. How this geometry impacts responses to volume overload remains unknown. We compared left ventricular size between English springer spaniels and two similarly sized sporting breeds (Border collies and Labrador retrievers) in naturally occurring chronic left ventricular volume loading conditions (mitral regurgitation and patent ductus arteriosus [PDA]) to examine whether differences in remodelling responses exist between these breeds. Animals, materials and methodsWe searched records for cases of mitral regurgitation and PDA in three breeds. We recorded age, sex, presence of congestive heart failure (CHF), body weight and specific echocardiographic variables. We compared normalised measures of left ventricular size between breeds. Cases with CHF were further examined as a separate group. ResultsOne-hundred-and-ninety-one dogs were included: 110 with degenerative mitral valve disease, 42 with mitral dysplasia and 39 with PDA. One third of all cases had CHF. All measures of left ventricular size were larger in English springer spaniels in mitral regurgitation cases (P<0.001), whereas PDA cases did not differ. English springer spaniels with PDA resulting in CHF had larger systolic dimensions and volumes than similarly affected non-English Springer Spaniel dogs (P=0.003). ConclusionsEnglish springer spaniels have greater left ventricular dimensions when exposed to chronic mitral regurgitation, compared with Border collies and Labrador retrievers, but not when exposed to volume overload from a PDA. English springer spaniels differ in their left ventricular morphology from two other sporting breeds, supporting previous studies that they have a unique cardiac morphotype.

IMPACT OF LEFT VENTRICULAR VOLUME OVERLOAD AND SYSTOLIC PULMONARY ARTERY PRESSURE ON RIGHT VENTRICULAR SYSTOLIC FUNCTION IN PATIENTS WITH CHRONIC PRIMARY MITRAL AND AORTIC REGURGITATION USING THREE DIMENSIONAL ECHOCARDIOGRAPHY

Background: To compare the effects of left ventricular volume(LV) overload due to chronic organic mitral(MR) or aortic valve(AR) regurgitation on RV shape and function.Methods: We studied 40 patients with moderate-severe or severe primary MR (60±19 years, 52% were men) and 20 patients with moderate or severe AR (53±18 years, 81% were men). Three-dimensional echocardiography of LV and RV was performed to measure volumes and EF. RV fractional area change (FAC) was calculated and RV shape was assessed by calculating RV eccentricity index .Results: LV end-diastolic volume (EDVi) was significantly larger in the patients with AR than those with MR. RV EF and RV FAC were lower in pts with AR than in those with MR. RV eccentricity index was significantly higher in the AR group (2.5±0.6 vs 2.1±0.5, p=0.003). In both groups, LV EDVi showed positive correlations with RV shape (RV eccentricity: r= 0.693 for AR and r=0.399 for MR; p<0.001) and negative correlations with RV function (RV EF: r= -0.545 for AR and r=- 0.383 for MR, p <0.001; RV FAC: r=-0.816 for AR and r=-0.647 for MR, p<0.001).Moreover, LV sphericity index showed negative correlations with RV function (RVFAC: r= -0.512 for MR and r=-0.608 for AR,P=0.001;RV EF:r=-0.408 for MR and r=-0.469, P=0.004) and positive correlation with the RV shape (RV eccentricity index,r= 0.39 for MR and r=0.511, P<0.001) .On multivariable linear regression analysis, LV EDVi and LV sphericity index were found to be the only independent predictors of RV eccentricity index, EF and FAC.Conclusions: RV remodeling in chronic LV overload due to MR or AR occurs independent on PASP values. LV size and shape are the only independent predictors of RV geometry and function. Accordingly, chronic AR has a greater impact on RV than MR

Invasive assessment of microvascular function in patients with valvular heart disease.

The aim of this study was to investigate microvascular function in patients with valvular heart disease (VHD), which causes chronic left ventricular volume and/or pressure overload, therefore change in coronary microvascular hemodynamics. We prospectively enrolled 30 patients with VHD considered for surgery (10 aortic stenosis, 12 aortic regurgitation, and eight mitral regurgitation) and 30 controls. Intracoronary physiological assessments were performed in the unobstructed left anterior descending artery using a pressure-temperature sensor guidewire at rest and hyperemia. The index of microcirculatory resistance (IMR) was similar between the two groups (16.2±6.5 vs. 16.2±8.5, P=0.997), whereas coronary flow reserve (CFR) was lower in the VHD group compared with the controls (3.2±1.4 vs. 4.3±1.7, P=0.005). Resting and hyperemic coronary distal pressure, and hyperemic mean transit time were similar between VHD and controls, whereas resting mean transit time was significantly shorter (0.70±0.29 vs. 0.89±0.39, P=0.035) and baseline resting microvascular resistance was significantly lower in the VHD group compared with the controls (58.1±25.4 vs. 78.1±36.7, P=0.011). Patients with aortic stenosis showed numerically higher IMR values than aortic regurgitation, mitral regurgitation, and controls, although this was not statistically significant (20.4±6.9, P=0.14). CFR was significantly correlated with log high-sensitivity cardiac troponin T levels in patients with VHD (r=-0.523, P=0.004). CFR was reduced in patients with VHD compared with controls, despite similar microvascular function as assessed by IMR. This appeared to be mainly because of an increased resting coronary flow accompanied by a decreased resting coronary microvascular resistance rather than microvascular disease.

Comparison of two-dimensional echocardiography methods of ventricular volume quantification to cardiovascular magnetic resonance in left ventricular volume overload

Assessment of left ventricular dilation plays an important role in the management of left ventricular volume overload lesions. Various echocardiographic methods exist, such as the 5/6 area-length and biplane Simpsons, but their agreement with cardiac magnetic resonance imaging in patients with chronic left ventricular volume overload from a young age has not been assessed. This was a retrospective review of patients with moderate or worse aortic regurgitation, mitral regurgitation, or ventricular septal defect who underwent both studies within 6months. End-diastolic and systolic volumes and dimensions were measured by echocardiography using the 5/6 area-length, biplane Simpsons, and M-mode methods, and compared to cardiac MRI-derived volumes. The 5/6 area-length method showed the best agreement with MRI and remained consistent with increasing ventricular dilation. The biplane Simpsons and M-mode-based Teichholz method underestimated ventricular dilation and performed worse with increasing dilation. When comparing ventricular dimensions by M-mode, there was a non-linear relationship between linear dimension and MRI-derived volume. Linear dimension appeared to plateau with increasing ventricular dilation, leading to underestimation in severity of dilation. The 5/6 area-length method was superior to other echocardiographic methods of ventricular volume quantification when compared with MRI.

Chronic high-fat diet-induced obesity decreased survival and increased hypertrophy of rats with experimental eccentric hypertrophy from chronic aortic regurgitation.

BackgroundThe composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival.MethodsMale Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later.ResultsAs expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet.ConclusionsHF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2261-14-123) contains supplementary material, which is available to authorized users.

Circulation: Heart Failure Editors’ Picks

Summary : Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year. The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure–volume measurements, exercise testing, and cardiac MRI before and after the training. To the authors’ knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans. After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume. Conversely, alagebrium had little effect on exercise capacity or LV geometry. However, alagebrium showed a modest improvement in LV stiffness compared with placebo. This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training. Conclusions : Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.1 Summary : Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival. On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing. This single-center study examined the association of …

Circulation Editors’ Picks

<i>Circulation</i> Editors’ Picks

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Mitral Regurgitation: Current Trends in Diagnosis and Management

Mitral regurgitation is the most prevalent heart valve disorder in the United States. Individuals with mitral regurgitation may be asymptomatic or may present with dyspnea, orthopnea, fatigue, and/or heart rhythm disturbances. Long-standing mitral regurgitation causes chronic left ventricular volume overload, which leads to left ventricular dilation and contractile dysfunction. Without treatment, mitral regurgitation results in biventricular failure and death. Echocardiography is the preferred diagnostic test to assess the presence and severity of mitral regurgitation. Mitral valve surgery, the only effective treatment for patients with severe mitral regurgitation, is recommended early in the course of the disease to prevent the development of heart failure. Early recognition of mitral regurgitation and timely referral for mitral valve surgery significantly improve symptoms and long-term survival.

Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation.

This study was designed to answer two questions. First, does the left ventricular contractile dysfunction resulting from mitral regurgitation (MR) reflect a primary defect in the cardiac muscle cell? Second, what is the basis for any change in cellular contractile function that might be observed? Left ventricular volume overload was produced in 10 dogs by catheter transection of mitral chordae tendineae. Three months later in these and in seven control dogs, left ventricular contractile function was characterized by the end-ejection stress-volume relation (EESVR). Investigators who were blinded to these results then characterized the contractile performance of cardiac muscle cells, or cardiocytes, from these same left ventricles in terms of the viscosity (graded external load)-velocity relation. Finally, the tissue and cellular components of these same left ventricles were analyzed morphometrically. Both the left ventricles from the MR group and their constituent cardiocytes showed marked contractile abnormalities. By matching ventricles with cells from the same MR dogs, ventricular EESVR was correlated with cardiocyte peak sarcomere shortening velocity (SSV). The correlation coefficient between EESVR and SSV was 0.63, but between a size-independent measure of active ventricular stiffness and SSV, it was 0.88. No change in left ventricular interstitial volume fraction was found in MR dogs, but both ventricular and cellular contractile dysfunction strongly correlated with a decreased volume fraction of cardiocyte myofibrils. Last, in an attempt to relate the degree of contractile dysfunction to the hypertrophic response, left ventricular mass in the MR dogs was correlated with both cellular and ventricular contractile indexes; no significant correlation was found. Three conclusions are warranted by these studies. First, chronic left ventricular volume overload from mitral regurgitation leads to contractile defects at both the ventricular and cellular levels, the extent of which correlates well in individual animals. Second, no quantitative interstitial change resulted from MR. Taken together, these two findings strongly suggest that the contractile defect is intrinsic to the cardiocyte. Third, while the contractile abnormality in MR remains undefined, the most basic defects appear to be a combination of myofibrillar loss with the failure of compensatory hypertrophy to occur in response to progressive decrements in cellular and ventricular function.

Effect of aging on peak systolic left ventricular wall stress in normal subjects

Studies of cardiac mechanics in compensated heart muscle suggest that muscle hypertrophy is stimulated by long-term increases in peak myocardial wall stress. 1–6 Conditions leading to either chronic left ventricular (LV) pressure or volume overload generally result in an increase in LV wall stress (expressed as force per unit area). Increased systolic stress results in decreased LV performance unless compensatory hypertrophy develops to normalize systolic wall stress. Measurements of LV wall stress in patients with chronic LV volume or pressure overload should provide an excellent index of cardiac compensation that could be followed serially to permit detection of early myocardial decompensation such as an abnormal increase in wall stress due to inadequate hypertrophy. 4–6 The objectives of this study were to examine the relation of LV peak systolic wall stress to age and body surface area in normal subjects and to establish the normal range of values for LV peak systolic stress, taking age and body surface area into account. We have shown that in normal subjects, LV wall thickness increases with increasing age and body surface area, while LV internal dimensions decrease slightly with aging, but increase with increasing body surface area. 7–9 To determine the effect of age and body surface area on LV peak systolic (meridional) wall stress, we analyzed M-mode echocardiographic data previously recorded in an adult population without evidence of cardiovascular disease. 7–9

'Athlete's Heart' in Prepubertal Children

Bradycardia, cardiomegaly, heart murmurs, and ECG changes are typically observed in adult endurance athletes, but frequency of such changes among children involved in sports training is unclear. Pediatricians need to be aware of whether these features of the "athlete's heart" occur in their patients, because such features may mimic those of cardiac disease. Fourteen prepubertal competitive male swimmers were evaluated by physical examination, ECG and echocardiogram, and findings were compared to those of a group of active but nontrained control boys. Lower resting heart rates and echocardiographic manifestations of chronic left ventricular volume overload were observed among the swimmers. These changes were not manifest on physical examination, however, and no significant ECG alterations were identified among the athletes. These findings indicate that, although features of the athlete's heart are present in children involved in endurance training, seldom will these findings simulate heart disease or be apparent on routine clinical examination.

Effect of captopril on left ventricular dynamics in patients with chronic left ventricular volume overload.

In order to evaluate the acute effects of pharmacological blockade of the renin-angiotensinogen system in patients with chronic left ventricular volume overload, 50 mg of the converting enzyme inhibitor captopril were administered to 4 patients with aortic insufficiency and 5 patients with mitral regurgitation. Mean aortic pressure decreased from 108±17 to 89±18 mmHg (P<0.001) and systemic vascular resistance decreased from 2,300±1,087 to 1,540±547 dyn s cm−5 (p<0.01). Left ventricular filling pressures decreased significantly. This resulted in an increase in cardiac index from 2.6±0.8 to 2.9±0.7 1/min/m2 (p<0.001) and an increase in the forward stroke volume index from 31±7 to 37±7 ml/m2 (p<0.001). Left ventricular end-diastolic and end-systolic volumes decreased significantly (p<0.05). No changes in left ventricular ejection fractions and heart rate were observed. Regurgitant stroke volume was reduced from 58±27 to 32±9 ml/m2 (p<0.01) and the regurgitant fraction from 64±13 to 46±8% (p<0.001). Coronary sinus blood flow decreased from 174±57 to 144±58 ml/min (p<0.05); coronary vascular resistance remained constant. Myocardial oxygen consumption was reduced from 26±11 to 21±12 mlO2/min (p<0.05). Captopril, therefore, has benefical hemodynamic effects in patients with chronic left ventricular volume overload due to aortic or mitral incompetence. Cardiac performance is increased at reduced metabolic costs.

Comparative hemodynamic effects of digoxin vs nitroprusside in conscious dogs with aortocaval fistula-induced chronic left ventricular volume overload and normal systolic performance

We compared the effects of IV digoxin (0.04 mg/kg) and nitroprusside (NP) (1.2 and 1.8 μg/kg/min) on left ventricular (LV) performance in six preinstrumented conscious dogs with chronic volume overload and congestive heart failure (CHF) produced by an aortocaval fistula. At 3 and 6 hours after digoxin administration (serum level, 3.5 ± 0.6 ng/ml), there were no changes in heart rate, LV systolic (LVSP) and end-diastolic (LVEDP) pressures, LV dimensions, LV dP dt max , or percent minor diameter shortening as compared to control values in the resting state, after beta blockade, or during phenylephrine infusion. By contrast, NP produced a significant reduction ( p < 0.05) in LVEDP (16 ± 3 to 10 ± 3 mm Hg) at the smaller dose which caused no change in mean aortic pressure. The larger dose of NP further reduced LVEDP and evoked significant ( p < 0.05) decreases in LVSP (124 ± 5 to 117 ± 7 mm Hg), mean aortic pressure (85 ± 3 to 78 ± 5 mm Hg), and LV end-diastolic dimension (LVEDD) (53.0 ± 5.5 to 52.0 ± 5.7 mm), while augmenting LV dP dt max (3288 ± 266 to 3647 ± 130 mm Hg/sec). Beta blockade with IV propranolol (2.0 mg/kg) prevented the rise in LV dP dt max after high-dose NP administration but did not alter the reductions in mean aortic pressure, LVEDP, and LVEDD. This study indicates that NP, but not digitalis, has a favorable effect on LV hemodynamics in the volume-overloaded heart with normal LV systolic contraction and high-output CHF resulting from increased blood volume and reduced LV diastolic compliance. At least part of the apparent improvement in LV performance observed with high-dose NP is sympathetically mediated since it can be attenuated by beta blockade.

Early changes in left ventricular size and function after correction of left ventricular volume overload

The ability to predict early postoperative left ventricular size and function in patients with isolated aortic or mitral regurgitation was determined utilizing multigated blood pool imaging before and 2 to 4 weeks after valve replacement (aortic valve, 20 patients; mitral valve, 20 patients). Early postoperatively, ejection fraction decreased significantly (p <0.001) in both patient groups (from 0.55 ± 12 to 0.40 ± 0.14 [mean ± 1 standard deviation] in patients with aortic regurgitation and from 0.66 ± 0.09 to 0.48 ± 0.11 in patients with mitral regurgitation). The decrease in ejection fraction was associated with a large decrease in stroke volume with minimal or no change in end-systolic volume; it was unrelated to the preoperative ejection fraction. Early postoperative ejection fraction correlated best with preoperative end-systolic volume and was normal in 14 (67 percent) of 21 patients with a preoperative ejection fraction above 0.60; 4 (27 percent) of 15 patients with a preoperative ejection fraction of 0.50 to 0.60; and in 0 of 4 patients with a preoperative ejection fraction below 0.50 (p <0.05). In addition, a repeated scan in 16 patients late (1 to 2 years) after operation showed a further reduction in endsystolic volume in patients with aortic regurgitation with an increase in ejection fraction toward preoperative values. There was no significant change in patients with mitral regurgitation. End-diastolic volume decreased significantly (p <0.001) early postoperatively (from 162 ± 60 to 102 ± 41 ml/m 2 in patients with aortic regurgitation and from 131 ± 40 to 78 ± 30 ml/m 2 in patients with mitral regurgitation). This decrease was closely related to a decrease in stroke volume and was unrelated to preoperative ejection fraction. Early postoperative end-diastolic volume correlated best with the preoperative end-systolic volume. The major part of the reduction in end-diastolic volume occurred within 2 weeks of valve replacement. Removal of chronic left ventricular volume overload due to aortic or mitral regurgitation produces a decrease in ejection fraction and end-diastolic volume. The early reduction is in part a result of altered loading conditions and may not necessarily imply alterations in myocardial contractile function. The reduction in ejection fraction appears to persist in patients with mitral regurgitation.

Ventricular volume overload alters cardiac output distribution in rats during exercise.

A rat model for chronic left ventricular volume overload (a-v fistula, 2 mo) was used to test the effects of acute exhaustive treadmill exercise (EX) (5 min, 70 ft/min, 0 degrees grade) on cardiocirculatory hemodynamics and cardiac output (CO) distribution during heart failure (HF). Control (C) and HF rats were studied at rest (R) and during the last minute of EX. Heart rate (HR), mean arterial pressure (MAP), and left ventricular end-diastolic (LVEDP) pressure were recorded and CO, blood flow (BF) to various regions, and total CO distribution were determined by the radioactive microsphere technique. In HF, biventricular hypertrophy and elevated LVEDP at R were correlated with an average shunt size equaling 37% of total CO. In both groups, CO and HR rose during EX with no change in MAP. Systemic CO in HF was reduced compared to C during both R and EX. BF to splanchnic, renal, cutaneous, and testicular circulations was compromised at R in HF, whereas only skeletal muscle BF was compromised in HF during EX. Data for CO distribution suggest that the major effect of HF during R was increased delivery to the coronary and the skeletal muscle beds at the expense of the cutaneous and renal beds, whereas %CO to the cerebral, hepatic, and gastrointestinal beds was spared. During EX, %CO to skeletal muscle beds in HF was attenuated compared to C, whereas that to the coronary bed was increased with no change in other regions.