Changes In Cardiac Size Research Articles

Changes in blood biomarkers correlate with changes in cardiac size and function in patients with tetralogy of Fallot

IntroductionPatients after surgical correction of Tetralogy of Fallot (ToF) often show adverse cardiac remodeling. To better understand the underlying biological processes, we studied the relation between changes in blood biomarkers and changes in biventricular size and function as assessed by cardiac magnetic resonance imaging (CMR). MethodsThis study included 50 ToF patients, who underwent blood biomarker and CMR analysis at least twice between 2002 and 2018.34 (68 %) of these patients were male. Patients had an average age of 16.1 at first visit. Biomarkers were chosen based on earlier research by our group and included: NT-proBNP, ST2, GDF-15, DLK-1, IGFBP-1/7, and FABP-4. Pearson correlations coefficients (rpearson) were determined to quantify the relationship between changes in biomarkers and CMR measurements. ResultsFor changes in parameters of right ventricular (RV) size significant correlations were observed with changes in NT-proBNP, ST-2, GDF-15, IGFBP7 and FABP-4 (rpearson between 0.28 and 0.51). Correlations with NT-proBNP were driven by changes in RV size induced by pulmonary valve replacement (n = 9). For LV serial size changes, significant correlations were noted with changes in NT-pro-BNP, ST-2, GDF-15 and FABP-4 (rpearson between 0.32 and 0.52). ConclusionIn clinically stable ToF patients changes in right and left ventricular size and function correlated with alterations in blood biomarkers of inflammation and immune response to stress.

Exercise-induced changes in myocardial glucose utilization during periods of active cardiac growth

Exercise training can promote physiological cardiac growth, which has been suggested to involve changes in glucose metabolism to facilitate hypertrophy of cardiomyocytes. In this study, we used a dietary, in vivo isotope labeling approach to examine how exercise training influences the metabolic fate of carbon derived from dietary glucose in the heart during acute, active, and established phases of exercise-induced cardiac growth. Male and female FVB/NJ mice were subjected to treadmill running for up to 4 weeks and cardiac growth was assessed by gravimetry. Cardiac metabolic responses to exercise were assessed via in vivo tracing of [13C6]-glucose via mass spectrometry and nuclear magnetic resonance. We found that the half-maximal cardiac growth response was achieved by approximately 1 week of daily exercise training, with near maximal growth observed in male mice with 2 weeks of training; however, female mice were recalcitrant to exercise-induced cardiac growth and required a higher daily intensity of exercise training to achieve significant, albeit modest, increases in cardiac mass. We also found that increases in the energy charge of adenylate and guanylate nucleotide pools precede exercise-induced changes in cardiac size and were associated with higher glucose tracer enrichment in the TCA pool and in amino acids (aspartate, glutamate) sourced by TCA intermediates. Our data also indicate that the activity of collateral biosynthetic pathways of glucose metabolism may not be markedly altered by exercise. Overall, this study provides evidence that metabolic remodeling in the form of heightened energy charge and increased TCA cycle activity and cataplerosis precedes cardiac growth caused by exercise training in male mice.

Toxicity Studies of Cardiac-Targeting Peptide Reveal a Robust Safety Profile.

Targeted delivery of therapeutics specifically to cardiomyocytes would open up new frontiers for common conditions like heart failure. Our prior work using a phage display methodology identified a 12-amino-acid-long peptide that selectively targets cardiomyocytes after an intravenous injection in as little as 5 min and was hence termed a cardiac-targeting peptide (CTP: APHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension to the development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed with the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10 µM of Cyanine-5.5-labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by extensive studies in stably transfected cell lines for several GPCR-coupled receptors. Positive data for GPCR-coupled receptors were interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting CTP (150 µg/Kg) in 60, 6-week-old, wild-type CD1, male/female mice (1:1), with cohorts of mice euthanized on days 0, 1, 2, 7, and 14 with inhalational CO2, followed by blood collection via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal, and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after CTP (150 µg/Kg) injection to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. No significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed using RT-qPCR. CTP (10 mg/Kg) injections led to no change in blood pressure. Blood counts and chemistries showed no evidence of significant hematological, hepatic, or renal toxicities. Lastly, there was no difference in cardiac function, size, or mass acutely in response to CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies using good laboratory practices are needed with prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated.

Abstract P1176: What Is The Nature Of The Hypertrophic Response Contributing To Pregnancy-induced Cardiac Growth And Its Reversal?

During pregnancy, the maternal heart undergoes physiological cardiac growth, reversing following parturition; however, the contributing underlying processes are largely unknown. Changes in cardiac metabolism appear to be associated with cardiac growth through a reduction in glucose catabolism. We have also shown that several cardiac metabolic transcripts, proteins, and liver-derived metabolites that are elevated during pregnancy are associated with cardiac growth. However, the nature of the hypertrophic response observed in the maternal heart is unclear. Therefore, this study aimed to examine the metabolic and hypertrophic changes associated with pregnancy-induced cardiac growth and reversal. Studies revealed that both heart weight (HW: TL; p < 0.0001) and liver weight (LIV: TL; p <0.0001) were highest in lactating 1-week post-birth (PB) mice versus mid-pregnant (8 d), late-pregnant (LP; 16 d), and non-pregnant (NP) 12-week-old FVB/NJ mice. Of note, we also found that HW: TL ( p < 0.01) and LIV: TL ( p < 0.0001) were significantly reduced in non-lactating 1-week post-birth mice (PBNL) compared with PB mice. However, the changes in cardiac size observed during pregnancy and post-birth were not associated with changes in either cardiomyocyte cross-sectional area or cardiac fluid content. Hearts and livers remained significantly larger, irrespective of lactation status, following parturition through 6 weeks post birth (PB) versus NP. Consistent with these changes, we found significant reductions in Pdk4 protein between 1- and 3-week PB and PBNL groups that were reversed by six weeks postpartum and a substantial increase in Pdk4 expression at six weeks postpartum, respectively. Interestingly, we see a sustained increase in cardiac Bdh1 expression that persisted at six weeks postpartum, which could contribute to the sustained increases in HW: TL versus NP. Changes in lactation status and metabolism are likely contributing to similar patterns of growth seen in the heart and liver during and following pregnancy. The maternal hypertrophic response is considered eccentric due to the absence of changes in myocyte cross-sectional area and cardiac fluid content.

Effects of pregnancy on cardiac structure and function in women with sickle cell anemia: a longitudinal comparative study

Background Sickle cell anemia is the commonest hemoglobinopathy in pregnant Nigerian women, and cardiac manifestations are a significant feature of the disease especially in pregnancy. Pregnant women with sickle cell anemia are at high risk of morbidity and mortality and cardiac dysfunction in them increases this risk and may compromise their post-partum health. Objective To evaluate the cardiac size and function in women with sickle cell anemia (HbSS) during late pregnancy and postpartum. Methodology This was a longitudinal comparative study in which 40 women, consisting of 20 pregnant HBSS and 20 pregnant HBAA women controls, were recruited. Echocardiography was performed in the third trimester of pregnancy and 6 weeks postpartum. Results There was a decrease in the mean left atrial diameter (p < .001), left ventricular diameter in diastole (p = .041), and left ventricular mass (p = .004) of HBSS women in the postpartum period compared to their antepartum state. In contrast, there was no significant difference in most cardiac dimensions of pregnant vs postpartum HBAA women. There was no significant change in cardiac function in the pregnant vs postpartum states in both study groups. There were significant differences in cardiac size but not function when comparing HBSS and HBAA women in pregnancy and postpartum. Conclusion Changes in cardiac size of sickle cell women in pregnancy does not appear to affect cardiac function during pregnancy and in the puerperium, suggesting that the increased size may purely be a response to their chronic anemic state. Studies following women up for longer periods including those with co-morbidities are recommended

Abstract 10080: Myocardial Physiological Responses to the Third Trimester of Healthy Pregnancy

Background: Pregnancy requires significant cardiometabolic adaptation and is therefore considered a “stress test” for future cardiovascular disease. Cardiovascular magnetic resonance (CMR) allows evaluation of cardiac structure, function and tissue characteristics with excellent reproducibility. There is scarcity of CMR data on pregnancy-associated cardiovascular adaptive changes. Moreover, no studies to date assessed the physiological impact of pregnancy on cardiac high energy phosphate metabolism, measured as the phosphocreatine (PCr)/ATP ratio, using 31 Phosphorus magnetic resonance spectroscopy ( 31 P-MRS). Objectives: We aimed to investigate the physiological effects of pregnancy in women in the third trimester of a healthy singleton pregnancy on cardiac energetics, function and tissue characteristics using 31 P-MRS and CMR at 3T. Methods: Thirty pregnant women and fifteen age-matching nulliparous healthy female controls were recruited. Results: Clinical characteristics and CMR/ 31 P-MRS results are provided in Table1.Resting heart rates and cardiac output were higher in pregnancy, with no significant differences in left-ventricular volumes, mass or ejection fraction, diastolic function (mitral in-flow E/A), global longitudinal strain or MAPSE. There were subtle reductions in cardiac PCr/ATP in pregnancy. Compared to non-pregnant controls, myocardial T1 was 2% higher in pregnant women, whilst T2 was 5% lower. Conclusions: Healthy pregnancy was associated with no significant changes in cardiac size, mass or function. Consistent with the haemodynamic changes in pregnancy, subtle reductions in cardiac energetics were detected, though these remained within normal range.CMR is well tolerated in pregnancy and may play a role in assessing cardiac involvement in women at risk of perinatal complications, offering the opportunity of early initiation of risk modifying treatment and prevention of adverse maternal cardiovascular outcomes.

2706 km cycling in 2 weeks: effects on cardiac function in 6 elderly male athletes

ABSTRACTObjectives: Physiological effects of exercise on trained and untrained individuals have been studied extensively. Typically, young or middle-aged individuals are examined before and after short periods of vigorous exertion.Methods: We studied 6 elderly male athletes (61 ± 8 years (mean ± SD); baseline O2max 48 ± 5 ml·kg−1·min−1) with focus on cardiac function and biomarkers following 14 consecutive days of moderate intensity exercise. Cardiac dimensions, function, biomarkers, and other measures of cardiovascular health were examined at baseline and 2 and 28 h after the last day of cycling a total of 2706 km.Results: Data collected after the cessation of exercise on the 14th day revealed significant increases in average size of the left atrium (3.5 ± 0.4 to 4.0 ± 0.3 cm; p = 0.02) and left ventricular end systolic volume (47 ± 2 to 52 ± 5 ml; p = 0.004), with no other significant changes in cardiac size or function. Small, transient increases in cardiac biomarkers (troponin T, creatine kinase myocardial band, and N-terminal pro-brain natriuretic peptide) (p < 0.01) were observed 2 h after completion of cycling but no changes in systolic (including strain-analyses) or diastolic cardiac function were observed at rest. O2max was significantly lower at the 28 h time point than at baseline (p < 0.02). Plasma concentrations of total- (p < 0.01) and low-density lipoprotein-cholesterol (p < 0.01) were markedly lower after exercise. Systolic blood pressure was unchanged, but diastolic pressure was significantly lower after exercise than at baseline.Conclusions: The results suggest that repeated moderate intensity exercise in elderly men was associated with a transient increase in cardiac biomarkers while cardiac function remained unaltered. A favorable reduction in blood lipids and diastolic blood pressure were seen for >28 h after the end of activity. An unexplained symptomless severe plasma hyponatremia developed in 3 of 6 subjects 28 h after the end of activity.

Onset and Regression of Pregnancy-Induced Cardiac Alterations in Gestationally Hypertensive Mice: The Role of the Natriuretic Peptide System1

Pregnancy induces cardiovascular adaptations in response to increased volume overload. Aside from the hemodynamic changes that occur during pregnancy, the maternal heart also undergoes structural changes. However, cardiac modulation in pregnancies complicated by gestational hypertension is incompletely understood. The objectives of the current investigation were to determine the role of the natriuretic peptide (NP) system in pregnancy and to assess alterations in pregnancy-induced cardiac hypertrophy between gestationally hypertensive and normotensive dams. Previously we have shown that mice lacking the expression of atrial NP (ANP; ANP(-/-)) exhibit a gestational hypertensive phenotype. In the current study, female ANP(+/+) and ANP(-/-) mice were mated with ANP(+/+) males. Changes in cardiac size and weight were evaluated across pregnancy at Gestational Days 15.5 and 17.5 and Postnatal Days 7, 14, and 28. Nonpregnant mice were used as controls. Physical measurement recordings and histological analyses demonstrated peak cardiac hypertrophy occurring at 14 days postpartum in both ANP(+/+) and ANP(-/-) dams with little to no change during pregnancy. Additionally, left ventricular expression of the renin-angiotensin system (RAS) and NP system was quantified by real-time quantitative polymerase chain reaction. Up-regulation of Agt and AT(1a) genes was observed late in pregnancy, while Nppa and Nppb genes were significantly up-regulated postpartum. Our data suggest that pregnancy-induced cardiac hypertrophy may be influenced by the RAS throughout gestation and by the NP system postpartum. Further investigations are required to gain a complete understanding of the mechanistic aspects of pregnancy-induced cardiac hypertrophy.

Effect of Treadmill Training on Cardiac Size, Heart Rate and Muscle Mass in Healthy Dogs

The aim of this study was to evaluate changes in heart rate, cardiac size and muscle mass in healthy dogs during an aerobic training program. Dogs (n=9) had 10-min treadmill sessions twice a week for 12 weeks. Data were analyzed as repeated measures (SAS 9.0). Vertebral heart score (P<0.05) and left and right thigh circumferences (P<0.01) increased progressively, suggesting an adaptive response of dogs to aerobic treadmill training. We concluded that changes in cardiac size and muscle mass are usefulcan help to assess the effect of aerobic training in dogs.

Does echocardiography accurately reflect CMR-determined changes in left ventricular parameters following exercise training? A prospective longitudinal study

Cardiac adaptation in response to exercise has historically been described using echocardiography. Cardiac magnetic resonance (CMR), however, has evolved as a preferred imaging methodology for cardiac morphological assessment. While direct imaging modality comparisons in athletes suggest that large absolute differences in cardiac dimensions exist, it is currently unknown whether changes in cardiac morphology in response to exercise training are comparable when using echocardiography and CMR. Twenty-two young men were randomly assigned to undertake a supervised and intensive endurance or resistance exercise-training program for 24 wk. Echocardiography and CMR assessment of left ventricular (LV) mass, LV end-diastolic volume, internal cavity dimensions, and wall thicknesses were completed before and after training. At baseline, pooled data for all cardiac parameters were significantly different between imaging methods, while LV mass (r = 0.756, P < 0.001) and volumes (LV end-diastolic volume, r = 0.792, P < 0.001) were highly correlated across modalities. Changes in cardiac morphology data with exercise training were not significantly related when echocardiographic and CMR measures were compared. For example, posterior wall thickness increased by 8.3% (P < 0.05) when assessed using echocardiography, but decreased by 2% when using CMR. In summary, echocardiography and CMR imaging modalities produce findings that differ with respect to changes in cardiac size and volume following exercise training.

The effect of exercise training on left ventricular relaxation and diastolic suction at rest and during orthostatic stress after bed rest

A marked reduction in upright stroke volume (SV) contributes substantially to orthostatic intolerance after exposure to spaceflight or bed rest. It is unclear whether slowed left ventricular (LV) relaxation and diastolic suction contribute to the reduction in SV or whether these changes are influenced by exercise training while in bed. Twenty-seven healthy adults completed 5 weeks of -6 deg head-down bed rest (HDBR). During HDBR, nine subjects were sedentary (NOEX), while 18 performed near-daily rowing ergometry (EX). Left ventricular mass, SV, LV end-diastolic volume (LVEDV), pulmonary capillary wedge pressure and Doppler ultrasound indices of LV function were collected pre- and post-HDBR during supine rest (twice) and during reduced LV loading (lower body negative pressure; LBNP) and increased LV loading (saline infusion). Post-HDBR, LV mass increased in the EX group, but decreased in the NOEX group. The reduction in SV and LVEDV during supine rest and LBNP were greater with NOEX in comparison to EX after HDBR. Peak early mitral annular velocity, isovolumic relaxation time, early propagation velocity, a non-invasive index of early diastolic filling and ventricular diastolic suction, and peak global longitudinal early strain rate were slowed during supine rest after HDBR with NOEX; however, these variables were either unaltered or the reduction was less prominent with EX. Doppler ultrasound measures of early diastolic filling, ventricular relaxation and diastolic suction were not significantly affected during LV unloading by LBNP after HDBR in either group. All Doppler indices were restored to pre-HDBR levels in both groups during saline infusion to normalize LV filling pressure after HDBR. It is concluded that Doppler indices of dynamic LV filling were reduced in both groups after HDBR; however, these effects were more pronounced in the NOEX group. Irrespective of group, post-HDBR Doppler parameters were restored when LV filling pressure was increased to pre-HDBR levels during saline infusion. Therefore, the reduction in upright SV after HDBR is more influenced by changes in LV loading conditions, namely left atrial pressure in the setting of LV remodelling, rather than ventricular relaxation and diastolic suction.

Effect of Cardiac Resynchronization Therapy on Reverse Remodeling and Relation to Outcome

Cardiac resynchronization therapy (CRT) plus implantation of an implantable cardioverter defibrillator (ICD) reduced the risk of death or heart failure event in patients with mildly symptomatic heart failure, left ventricular dysfunction, and wide QRS complex compared with an ICD only. We assessed echocardiographic changes in patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial: Cardiac Resynchronization Therapy) to evaluate whether the improvement in outcomes with CRT plus an ICD was associated with favorable alterations in cardiac size and function. A total of 1,820 patients were randomly assigned to CRT plus an ICD or to an ICD only in a 3:2 ratio. Echocardiographic studies were obtained at baseline and 12 months later in 1,372 patients. We compared changes in cardiac size and performance between treatment groups and assessed the relationship between these changes over the first year, as well as subsequent outcomes. Compared with the ICD-only group, the CRT-plus-ICD group had greater improvement in left ventricular end-diastolic volume index (-26.2 versus -7.4 mL/m(2)), left ventricular end-systolic volume index (-28.7 versus -9.1 mL/m(2)), left ventricular ejection fraction (11% versus 3%), left atrial volume index (-11.9 versus -4.7 mL/m(2)), and right ventricular fractional area change (8% versus 5%; P<0.001 for all). Improvement in end-diastolic volume at 1 year was predictive of subsequent death or heart failure, with adjustment for baseline covariates and treatment group; each 10% decrease in end-diastolic volume was associated with a 40% reduction in risk (P<0.001). CRT resulted in significant improvement in cardiac size and performance compared with an ICD-only strategy in patients with mildly symptomatic heart failure. Improvement in these measures accounted for the outcomes benefit. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Pulmonary Artery Thrombosis in Experimental Angiostrongylus vasorum Infection Does Not Result in Pulmonary Hypertension and Echocardiographic Right Ventricular Changes

Dogs experimentally inoculated with Angiostrongylus vasorum develop severe pulmonary parenchymal lesions and arterial thrombosis at the time of patency. A. vasorum-induced thrombosis results in arterial hypoxemia, pulmonary hypertension (PH), and altered cardiac morphology and function. Six healthy Beagles experimentally inoculated with A. vasorum. Thoracic radiographs and arterial blood gas analyses were performed 8 and 13 weeks postinoculation (wpi) and 9 weeks posttherapy (wpt). Echocardiography was done before and 2, 5, 8, 13 wpi and 9 wpt. Invasive pulmonary artery pressure (PAP) measurements were obtained 8 wpi. Two untreated dogs were necropsied 13 wpi and 4 treated dogs 9 wpt. All dogs had patent infections at 7 wpi and clinical respiratory signs at 8 wpi. Moderate hypoxemia (median PaO2 of 73 and 74 mmHg) present at 8 and 13 wpi had resolved by 9 wpt. Echocardiographically, no evidence of PH and no abnormalities in cardiac size and function were discernible at any time point. PAP invasively measured at 8 wpi was not different from that of control dogs. Severe radiographic pulmonary parenchymal and suspected thrombotic lesions at 13 wpi were corroborated by necropsy. Most histopathologic changes had resolved at 9 wpt, but focal inflammatory, thrombotic, and fibrotic changes still were present in all dogs. In experimentally infected Beagles, pulmonary and vascular changes induced by A. vasorum are reflected by marked radiographic changes and arterial hypoxemia. These did not result in PH and echocardiographic changes in cardiac size and function.

Reduced cardiac functional reserve and quality of life in adults with GH deficiency

Patients with severe GH deficiency (GHD) suffer with a reduced quality of life in addition to diverse changes in cardiac size and performance. So far, the cardiac reserve ability to maintain the circulation during peak exercise has not been measured. We tested the hypothesis that patients with severe GHD have reduced cardiac reserve function compared with healthy controls and that this could explain, in part, their reduced quality of life. Eighteen patients with severe GHD and an assessment of GHD in adults (AGHDA) score > or =11 (mean 20.0, range 12-25) were studied and compared with 18 age-, sex- and body mass index-matched healthy controls. Peak cardiac power and cardiorespiratory fitness were investigated using noninvasive haemodynamic measurements during maximal cardiopulmonary exercise testing. Compared with matched controls, the cardiac power of GHD patients during exercise to volitional exhaustion was significantly reduced by 15% (mean +/- SD 4.4 +/- 1.0 W vs. 5.2 +/- 1.0 W, P = 0.02). Patients with GHD also had lower cardiac chronotropic reserve (peak heart rate 154 +/- 21/min vs. 174 +/- 11/min, P = 0.001) and a lower cardiac pressure-generating capacity (systolic blood pressure 160 +/- 25 mmHg vs. 200 +/- 15 mmHg, P < 0.0001). We found no correlation between any measure of peak cardiac power or function and the AGHDA score. Using this robust noninvasive method of assessing functional cardiac pumping capacity, we have for the first time shown that, while patients with severe GHD have a significantly impaired cardiac functional reserve associated with chronotropic incompetence and impaired pressure-generating capacity, this does not correlate with their reduced quality of life assessed using the current standard AGHDA score.

Is there a cardiomyopathy of obesity?

Obesity is associated with structural and functional changes in the heart. These changes may be precursors to more overt forms of cardiac dysfunction and heart failure. However, it is not known 1) whether cardiac hypertrophy in obese individuals results directly from increased adioposity or from the effects of comorbid conditions such as hypertension, diabetes, and sleep-disordered breathing and 2) whether functional changes (eg, mild reductions in systolic and diastolic function) in obese patients progress over time to the point where they cause heart failure, unless ischemic heart disease develops. Establishing a clear link between obesity and heart failure is complicated by the fact that obesity must be present for many decades before the risk of heart failure increases substantially. At present, there are no longitudinal studies of changes in cardiac size and function in humans with obesity. This article reviews data showing structural and functional changes in the heart in obesity and the evidence that these are or are not progressive over time. At present, we believe it is uncertain whether there is a true "cardiomyopathy of obesity."

Competition for Intrathoracic Space Reduces Lung Capacity in Patients With Chronic Heart Failure: A Radiographic Study

The purpose of this study was to determine the influence of changes in cardiac size on total lung volume in patients with chronic heart failure compared to control subjects.Forty-four patients and age-, gender-, and height-matched control participants were recruited. All participants underwent posteroanterior and lateral chest radiography for volumetric estimations of the total thoracic cavity (TTC), diaphragm, heart, and lungs. To assess the relationship between chronic heart failure severity and cardiac enlargement, patients with chronic heart failure were classified into groups based on New York Heart Association class, as follows: class I and II, n = 26 (group A); class III and IV, n = 18 (group B).There was no difference between the groups for TTC volume (TTCV) [p = 0.56]. Cardiac volumes were significantly different between all groups for both the absolute volumes (p < 0.001) were calculated as a percentage of TTCV (p < 0.001), with the largest cardiac volumes in group B (twice the volume of healthy control subjects). When expressed as a percentage of TTCV, there also was a clear reduction in lung volumes as a function of disease severity (p < 0.001).The present study demonstrates a close relationship between the severity of heart failure and cardiac size. These changes in cardiac size within a closed thoracic cavity may pose significant constraints on the lungs, resulting in reductions in lung volumes that likely play a major role in the restrictive breathing patterns often reported in patients with chronic heart failure.

Pericardial adaptation in severe chronic pulmonary hypertension. An intraoperative transesophageal echocardiographic study.

The pericardium both limits cardiac distension and accentuates ventricular interdependence. Although this effect appears minimal under normal circumstances, the pericardium markedly restricts acute cardiac enlargement. Animal studies have demonstrated gradual pericardial adaptation and expansion in chronic volume overload and cardiomegaly, but the pericardial response in humans with cardiac hypertrophy and enlargement has not been examined fully. To investigate this further, 14 patients with right ventricular hypertrophy and cardiomegaly secondary to chronic pulmonary thromboembolic disease and severe pulmonary hypertension were studied during pulmonary thromboendarterectomy. Simultaneous intraoperative transesophageal Doppler echocardiography and direct biventricular hemodynamic measurements were performed at steady state immediately before and after pericardiotomy. All hemodynamic variables showed no significant change before and after pericardiotomy, including heart rate (76 +/- 16 versus 75 +/- 15 beats per minute), mean pulmonary arterial pressure (46.3 +/- 11.1 versus 45.5 +/- 11.7 mm Hg), cardiac index (1.8 +/- 0.5 versus 2.0 +/- 0.6 l/min/m2), left ventricular end-diastolic pressure (5.9 +/- 5.7 versus 7.1 +/- 5.0 mm Hg), and right ventricular end-diastolic pressure (7.9 +/- 6.6 versus 8.0 +/- 6.7 mm Hg). Similarly, there were no significant changes in all Doppler echocardiographic parameters, including right ventricular end-diastolic area (23.2 +/- 5.7 versus 22.6 +/- 5.4 cm2), left ventricular end-diastolic area (15.3 +/- 5.9 versus 15.5 +/- 4.4 cm2), the position of the interventricular septum, and the Doppler-derived mitral inflow measures of diastolic function. The pericardium appears to have little influence on the marked cardiac and septal deformations seen in patients with chronic, severe right ventricular pressure overload and cardiomegaly. This study confirms that the human pericardium is capable of adapting over time to changes in cardiac size and geometry.

Cardiac and skeletal muscle adaptations to training in systemic hypertension and effect of beta blockade (metoprolol or propranolol)

Cardiovascular and peripheral adaptations to an aerobic conditioning program were studied in 30 hypertensive adults taking either placebo, β 1-selective β-adrenergic blocker (metoprolol) or β 1-nonselective β-adrenergic blocker (propranolol). The placebo group increased aerobic capacity (VO 2max) 24% (p < 0.002), largely explained by an increased peripheral arteriovenous (AV) oxygen difference with minimal changes in cardiac size and function. Resting blood pressure and total systemic resistance also decreased. The group taking a β-selective β blocker increased V̇O 2max 8% (p < 0.05), reduced resting blood pressure but had no significant change of AV oxygen difference or cardiac size or function. The group taking the β 1-nonselective β blocker propranolol had no increase inV̇O 2max, no decrease in resting blood pressure and no cardiovascular or peripheral adaptations to the exercise program. Thus, β 1-selective and β 1-nonselective β blockers attenuate conditioning in hypertensive patients to differing degrees, in each case by blocking peripheral mechanisms of conditioning.

Cardiovascular effects of intermittent drinking: assessment of a novel animal model of human alcoholism.

The development of a novel model of human alcoholism has involved the presentation of a 30% alcohol solution to Sprague-Dawley rats via a syringe-feeding needle apparatus. With twice daily intermittent drinking, rats consumed an equivalent of 7-8 g/kg body weight of alcohol, which represented 25% of total daily caloric intake. Alcohol was absorbed rapidly, as significant circulating concentrations were observed within 15 min of gavage, eventually peaking at approximately 200 mg% 1 h later. Hemodynamic recordings in the conscious state after a 10-week drinking program indicated a normotensive blood pressure at peak blood alcohol levels, yet a hypertensive response 24 h after the final drink at a time when blood alcohol was not detected. Alcoholic rats continued to gain weight in parallel with controls fed ad libitum throughout the study, and changes in cardiac size and indices of contractility were not affected by 10 weeks of intermittent drinking. Additionally, no histological evidence of cardiac muscle damage was observed in alcoholic animals. Our animal model closely resembles the clinical situation in terms of the pattern of alcohol consumption, circulating concentrations of alcohol and the percentage of caloric intake in the form of alcohol. The hemodynamic changes observed support the hypothesis that alcoholic hypertension may be a manifestation of withdrawal, as opposed to any direct pressor effect of alcohol itself.

Thyroxine-induced cardiac hypertrophy: time course of development and inhibition by propranolol.

To investigate the mechanism of thyroid hormone-induced cardiac hypertrophy, we have studied the in vivo changes in cardiac size and total myocardial content of both membrane and cytoskeletal enzymes in the rat after the administration of excess thyroid hormone. In response to 50 micrograms T4/day, there is a significant increase in heart rate and heart work associated with an increase in total heart size and protein content. Measurements of the specific activity of Na,K-ATPase and p-nitrophenol phosphatase demonstrate a small but significant increase in specific activity, while the specific activity of myosin ATPase is unchanged. To further probe the mechanism for T4-mediated hypertrophy we studied the in vivo effects of beta-adrenergic blockade on rat heart size. When animals were treated with both T4 and propranolol (10 mg/animal.day) cardiac hypertrophy was prevented. Propranolol alone at this dose did not affect heart rate, heart weight, or serum levels of T4 and T3. The present data suggest that 1) the hypertrophic response of the myocardium to excess thyroid hormone involves cytoplasmic as well as membrane proteins, 2) the increase in total myocardial protein, which can be blocked by propranolol, is indirectly mediated by increases in cardiac work rather than a direct effect of thyroid hormone.