Septal Function Research Articles

Abstract 18477: Left Ventricular Ejection Fraction is Not Sensitive Enough to Accurately Determine Timing of Surgical Referral for Asymptomatic Patients With Chronic Mitral Regurgitation

The current clinical guidelines for asymptomatic patients with chronic MR, utilize EF to trigger surgical referral. We hypothesize that 1) EF is not sensitive enough to detect the earliest contractile injury in chronic MR and 2) injury associated with chronic MR is not global but rather heterogeneous, occurring regionally and predictably, and prior to the onset of global left ventricular (LV) dysfunction. Asymptomatic: patients with chronic MR and normal left ventricular EF by echocardiography (n=14) underwent cardiac MRI with tissue tagging. The point-specific comparison (at 15,300 LV grid points) of multiple strain parameters to a 60-patient normal human strain database allowed normalization of patient-specific regional contractile function. Data was color-contour mapped over patient-specific 3D geometry, then further averaged across six LV regions (anterior, anterolateral, posterolateral, posterior, posteroseptal, anteroseptal). Global: LV function by multiparametric strain analysis was normal for all 14 MR patients when compared to normal controls. Despite overall preserved global LV function, the LV septum demonstrated significantly worse normalized contractile function when compared to other regions of the LV ( 0.07 ± 0.42 vs -0.40 ± 0.54, p=0.009 ). Hyper-contractile regions (lateral walls) appeared to compensate (p=0.002) for the reduced septal contractile function thereby masking injury detection by global indices. In asymptomatic MR patients with normal global LV function, contractile injury is heterogeneous, with a consistent distribution pattern identifying the LV septum as being injured earliest with contractile compensation by other regions. Rather than relying upon global LV contractile metrics, which does not detect early onset of injury, asymptomatic chronic MR patients should be followed with surveillance of early injury (or “sentinel”) LV regions (LV septum) with high-resolution metrics of regional contractile function.

Risk prediction of ventricular arrhythmias and myocardial function in Lamin A/C mutation positive subjects

Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects. We included 41 Lamin A/C mutation-positive subjects. PR-interval and occurrence of VA were recorded. Left ventricular (LV) myocardial function was assessed as ejection fraction and speckle tracking longitudinal strain by echocardiography. Magnetic resonance imaging was performed to assess fibrosis in a selection of subjects. Ventricular arrhythmias were documented in 21 patients (51%). Prolonged PR-interval was the best predictor of VA (P < 0.001). Myocardial function by strain was reduced in the interventricular septum compared with the rest of the LV segments (-16.7% vs. -18.7%, P = 0.001) and correlated to PR-interval (R = 0.41, P = 0.03). Myocardial fibrosis was found exclusively in the interventricular septum and only in patients with VA (P = 0.007). PR-interval was longer in patients with septal fibrosis compared with those without (320 ± 66 vs. 177 ± 40 ms, P < 0.001). Prolonged PR-interval was the best predictor of VA in Lamin A/C mutation-positive subjects. Electrical, mechanical, and structural cardiac properties were related in these subjects. Myocardial function was most reduced in the interventricular septum and correlated to prolonged PR-interval. Myocardial septal fibrosis was associated with prolonged PR-interval and VA. Localized fibrosis in the interventricular septum may be the mechanism behind reduced septal function, atrioventricular block and VA in Lamin A/C mutation-positive subjects.

Right Ventricular and Septal Function in Patients with Pulmonary Hypertension

Pulmonary hypertension (PHT) exacerbates the functions of both ventricles. This prospective, randomised study was planned to investigate the effects of PHT on kinetics of both ventricles and the septum. Twenty-five patients were randomly selected among the patients who had been planned to undergo mitral valve replacement (MVR) because of isolated mitral stenosis and divided into two groups according to their preoperative pulmonary artery pressure (PAP) values. Blood pool gated single photon emission tomography (BPGS) and transthoracic echocardiography were performed. Ventricles' regional, global and functional parameters were also assessed by using pulsed wave Doppler tissue imaging (DTI). Preoperative and postoperative PAP of the group 1 (PAP < 50 mmHg) were 40.0 ± 2.8 and 30.0 ± 2.6 mmHg (p = 0.03), group 2 (PAP ≥ 50 mmHg) were 71.9 ± 4.7 and 50.6 ± 3.5 mmHg (p < 0.05). The global right and left ventricle scores were decreased after the operation. The decrement was only significant in group 2. Considering the septal kinetics, right ventricle septal score was decreased from 7.6 to 3.3 (p < 0.05) in group 1, from 3.8 to 1.6 (p < 0.05) in group 2 postoperatively. Following MVR, a decrement in PAP values, and an improvement in ventricular function, especially in the right ventricular and septal kinetics were achieved. Furthermore, it was found that both DTI and BPGS techniques are beneficial to investigate the functional changes postoperatively and in the follow-up period of the patients who undergo mitral valve surgery.

Ventricular Septal Dysfunction After Surgical Closure of Multiple Ventricular Septal Defects

We assessed the global and regional ventricular septal functions using conventional echocardiography and two-dimensional speckle tracking imaging in children with postoperative multiple ventricular septal defects. Thirty-six children were studied: 16 with postoperative multiple ventricular septal defects and 20 normal control subjects. In children with multiple ventricular septal defects, 60 ventricular septal defects were closed using one of three different techniques (patch closure, the sandwich technique, direct closure). Speckle tracking imaging was applied to three short-axis echocardiographic images. The total patch area used in the multiple ventricular septal defects group was correlated with the postoperative ejection fraction (r=0.703) and Tei index (r=0.778). The global septal peak systolic radial displacement and global septal peak systolic radial strain in the multiple ventricular septal defects group were significantly lower than those observed in the control subjects. The peak systolic radial strain in the segments closed with patches and the peak systolic radial displacement in the segments closed with the felt sandwich technique were significantly lower than those observed in the intact septal segments. No significant regional functional depressions were identified in the segments that were closed directly. The postoperative ventricular global and septal functions were significantly reduced in children with multiple ventricular septal defects, especially in the cases with complex congenital heart disease and that were closed with large prosthetic materials. These results suggest that an effort to minimize the use of patch materials may lead to preserved postoperative ventricular function.

Right Ventricular Systolic Function in Organic Mitral Regurgitation

Background— To assess the prevalence, determinants, and prognosis value of right ventricular (RV) ejection fraction (EF) impairment in organic mitral regurgitation. Methods and Results— Two hundred eight patients (62±12 years, 138 males) with chronic organic mitral regurgitation referred to surgery underwent an echocardiography and biventricular radionuclide angiography with regional function assessment. Mean RV EF was 40.4±10.2%, ranging from 10% to 65%. RV EF was severely impaired (≤35%) in 63 patients (30%), and biventricular impairment (left ventricular EF&lt;60% and RV EF≤35%) was found in 34 patients (16%). Pathophysiologic correlates of RV EF were left ventricular septal function (β=0.42, P &lt;0.0001), left ventricular end-diastolic diameter index (β=−0.22, P =0.002), and pulmonary artery systolic pressure (β=−0.14, P =0.047). Mitral effective regurgitant orifice size (n=84) influenced RV EF (β=−0.28, P =0.012). In 68 patients examined after surgery, RV EF increased strongly (27.5±4.3–37.9±7.3, P &lt;0.0001) in patients with depressed RV EF, whereas it did not change in others ( P =0.91). RV EF ≤35% impaired 10-year cardiovascular survival (71.6±8.4% versus 89.8±3.7%, P =0.037). Biventricular impairment dramatically reduced 10-year cardiovascular survival (51.9±15.3% versus 90.3±3.2%, P &lt;0.0001; hazard ratio, 5.2; P &lt;0.0001) even after adjustment for known predictors (hazard ratio, 4.6; P =0.004). Biventricular impairment reduced also 10-year overall survival (34.8±13.0% versus 72.6±4.5%, P =0.003; hazard ratio, 2.5; P =0.005) even after adjustment for known predictors ( P =0.048). Conclusions— In patients with organic mitral regurgitation referred to surgery, RV function impairment is frequent (30%) and depends weakly on pulmonary artery systolic pressure but mainly on left ventricular remodeling and septal function. RV function is a predictor of postoperative cardiovascular survival, whereas biventricular impairment is a powerful predictor of both cardiovascular and overall survival.

Increased amount of interstitial fibrosis predicts ventricular arrhythmias, and is associated with reduced myocardial septal function in patients with obstructive hypertrophic cardiomyopathy

Reduced echocardiographic strain is associated with ventricular arrhythmias in hypertrophic cardiomyopathy (HCM) patients. The aim of this cross-sectional study was to investigate which type of histological fibrosis contributes to ventricular arrhythmias and reduced septal longitudinal strain, in obstructive HCM-patients with or without additional coronary artery disease (CAD) and/or hypertension (HT). Sixty-three HCM-patients (mean age 57 ± 13 years) were included. Strain by speckle tracking echocardiography was performed prior to either percutaneous transluminal septal ablation (n = 37) or septal myectomy (n = 26). In 24 patients myectomy specimens were available (histology population) and allowed determination of %area of interstitial and replacement fibrosis. Twenty-nine (46%) patients had concomitant CAD and/or HT, and 15 (24%) experienced ventricular arrhythmias defined as documented ventricular tachycardia or arrhythmogenic suspected syncope. The patients with ventricular arrhythmias had lower septal longitudinal strain compared with those without arrhythmias (-9.0 ± 4.0 vs. -13.6 ± 5.6%, P = 0.006). In the histology population reduced septal longitudinal strain correlated to interstitial (R(2) = 0.36 P = 0.003), but not to replacement fibrosis (R(2) = 0.03 P = 0.43). By logistic regression analyses, interstitial fibrosis predicted ventricular arrhythmias (OR 1.16, 95% CI 1.02-1.32, P = 0.03), while replacement fibrosis did not (OR 1.22, 95% CI 0.93-1.59, P = 0.15). Total amount of fibrosis was a marker of ventricular arrhythmias in obstructive HCM-patients. Interstitial fibrosis seemed to be more important compared with replacement fibrosis in arrhythmogenesis, and was related to reduced septal myocardial function. These findings suggest that interstitial fibrosis may play an important role as the arrhythmogenic substrate, and that strain echocardiography can help detection of patients at risk.

156: Prevalence, determinants and prognosis value of right ventricular function impairment in organic mitral regurgitation

Pevalence, determinants and prognosis value of right ventricular (RV) ejection fraction (EF) in organic mitral regurgitation (MR). Two-hundred eight pts (62±13 years, 138 males, AF 57 pts) with organic MR referred to surgery underwent an echocardiography and left ventricular (LV) and RV radionuclide angiography. LV and RV regional function was assessed. Mean RV EF was 40.7±10.1%, ranging from 10 to 65%. Sixty pts (29%) had a RV EF ≤35%. In multivariate analysis, LV septal function (LV EF 8: β=0.56, P<0.0001; LV EF 9: β=0.22, P=0.046), LV EDD index (β=−0.27, P<0.0001) and PASP (r=−0.19, P=0.008) were predictors of RVEF. In the subgroup with MR quantitation (n=85) predictor of RV EF was mitral ERO (β=−0.30, P=0.007). After surgery, RV EF increased strongly (27.5±4.3 to 37.9±7.3, P<0.0001) in pts with preoperative RV EF ≤35% while it did not change in pts with RV EF>35% (46.0±6.9 to 46.1±8.2, P=0.91). Independent predictors of postoperative RV EF were preoperative RV EF (β=0.32, P=0.013) and TR ≥grade 2 (β=–0.22, P=0.036) while LV septal function (LV EF 8, β=0.24, P=0.069) was marginally predictive. Fifty-seven pts died during post-operative follow-up of 7.1±4.3 years. Pts with RV EF ≤35% compared with RVEF>35% had a similar survival rate at 10 years (63.6±8.7% versus 68.8±5.3%, P=0.68), but cardiovascular mortality was higher (25.3±8.0% versus 8.1±3.5%, P=0.03; HR=2.67, 95% CI 1.06-6.76, P=0.037). RV EF was not a predictive factor of operative mortality. In a Cox model, NYHA class, CABG, and left atrial diameter, but not RV EF, were independent predictors of overall mortality. In organic MR RV function depends not only on PASP but mainly on LV remodeling and septal function, and improves strongly after surgery. RV EF is a predictor of cardiovascular mortality in univariate but not in multivariate analysis. Hence, impaired RV EF before surgery is not a sufficient argument to deny surgery in patients with organic MR.

Amniotic Fluid or Its Fatty Acids Produce Actions Similar to Diazepam on Lateral Septal Neurons Firing Rate

Human amniotic fluid (AF) contains eight fatty acids (FATs), and both produce anxiolytic-like effects in adult rats and appetitive responses in human newborns. The medial amygdala and lateral septal nucleus function are related to social behavior, but the action of AF or its FATs in this circuit is known. We obtained 267 single-unit extracellular recordings in Wistar rats treated with vehicle (1 mL, s.c.; n = 12), human AF (1 mL, s.c.; n = 12), a FAT mixture (1 mL, s.c.; n = 13), diazepam (1 mg/kg, i.p.; n = 11), and fluoxetine (1 mg/kg, p.o.; n = 12). Compared with the vehicle group, the spontaneous septal firing rate in the AF, FAT mixture, and diazepam groups was the lowest and in the fluoxetine group the highest. Cumulative peristimulus histograms indicated that the significant change in septal firing occurred only in the AF and FAT mixture groups and exclusively in those neurons that increased their firing rate during amygdala stimulation. We conclude that human AF and its FATs produce actions comparable to anxiolytic drugs and are able to modify the responsivity of a circuit involved in social behavior, suggesting facilitation of social recognition processes by maternal-fetal fluids.

Abstract 9463: Septal Myocardial Function is reduced in Carriers of Lamin A/C mutations and related to Atrioventricular Block, Ventricular Tachycardia and Septal Fibrosis

Background: Mutations in the Lamin A/C gene may cause dilated cardiomyopathy accompanied by atrioventricular (AV) block, atrial fibrillation and ventricular tachycardia (VT). VTs are frequent and commonly occur before development of dilated cardiomyopathy. Mechanisms of AV block and VT in these patients are not fully understood. Methods: We included 41 Lamin A/C mutation carriers with LV (left ventricular) EF 55±13%. PR interval from resting ECG and occurrence of VT by Holter monitoring and ICDs were recorded. Global and LV septal myocardial function were assessed by echocardiographic speckle tracking strain analysis. Nine patients were eligible for magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE) to assess presence and distribution of myocardial fibrosis. Results: VT was documented in 21 patients (51%). Prolonged PR interval (p&lt;0.001), presence of AV block (p&lt;0.001) and reduced global longitudinal strain (p=0.01) were markers of VT, while LVEF was not (p=0.55). LV septal function was markedly reduced compared to function in the rest of the left ventricle (strain -16.7% vs. -18.7%, p=0.001). Prolonged PR interval correlated with reduced LV septal function (R=0.41, p=0.03). By LGE MRI, 4/5 patients (80%) with documented VT showed LV septal fibrosis while no fibrosis was detected in 4/4 (100%) patients without VT (p=0.05). Fibrosis by MRI was located exclusively in the LV septum. PR interval was longer in patients with LV septal fibrosis compared to those without (320±26 vs. 172±66ms, p=0.002). Conclusion: In Lamin A/C mutation carriers, myocardial function was most decreased in the LV septum and correlated to prolonged PR interval. Prolonged PR interval was a marker of VT. Myocardial LV septal fibrosis was associated with prolonged PR interval and VT. Localized fibrosis in the LV septum may be the mechanism behind AV block, VT and reduced LV septal function in Lamin A/C mutation carriers.

Systems genetics of the lateral septal nucleus in mouse: heritability, genetic control, and covariation with behavioral and morphological traits.

The lateral septum has strong efferent projections to hypothalamic and midbrain regions, and has been associated with modulation of social behavior, anxiety, fear conditioning, memory-related behaviors, and the mesolimbic reward pathways. Understanding natural variation of lateral septal anatomy and function, as well as its genetic modulation, may provide important insights into individual differences in these evolutionarily important functions. Here we address these issues by using efficient and unbiased stereological probes to estimate the volume of the lateral septum in the BXD line of recombinant inbred mice. Lateral septum volume is a highly variable trait, with a 2.5-fold difference among animals. We find that this trait covaries with a number of behavioral and physiological phenotypes, many of which have already been associated with behaviors modulated by the lateral septum, such as spatial learning, anxiety, and reward-seeking. Heritability of lateral septal volume is moderate (h 2 = 0.52), and much of the heritable variation is caused by a locus on the distal portion of chromosome (Chr) 1. Composite interval analysis identified a secondary interval on Chr 2 that works additively with the Chr 1 locus to increase lateral septum volume. Using bioinformatic resources, we identified plausible candidate genes in both intervals that may influence the volume of this key nucleus, as well as associated behaviors.

NADH Fluorescence Imaging of Isolated Biventricular Working Rabbit Hearts

Since its inception by Langendorff1, the isolated perfused heart remains a prominent tool for studying cardiac physiology2. However, it is not well-suited for studies of cardiac metabolism, which require the heart to perform work within the context of physiologic preload and afterload pressures. Neely introduced modifications to the Langendorff technique to establish appropriate left ventricular (LV) preload and afterload pressures3. The model is known as the isolated LV working heart model and has been used extensively to study LV performance and metabolism4-6. This model, however, does not provide a properly loaded right ventricle (RV). Demmy et al. first reported a biventricular model as a modification of the LV working heart model7, 8. They found that stroke volume, cardiac output, and pressure development improved in hearts converted from working LV mode to biventricular working mode8. A properly loaded RV also diminishes abnormal pressure gradients across the septum to improve septal function. Biventricular working hearts have been shown to maintain aortic output, pulmonary flow, mean aortic pressure, heart rate, and myocardial ATP levels for up to 3 hours8. When studying the metabolic effects of myocardial injury, such as ischemia, it is often necessary to identify the location of the affected tissue. This can be done by imaging the fluorescence of NADH (the reduced form of nicotinamide adenine dinucleotide)9-11, a coenzyme found in large quantities in the mitochondria. NADH fluorescence (fNADH) displays a near linearly inverse relationship with local oxygen concentration12 and provides a measure of mitochondrial redox state13. fNADH imaging during hypoxic and ischemic conditions has been used as a dye-free method to identify hypoxic regions14, 15 and to monitor the progression of hypoxic conditions over time10. The objective of the method is to monitor the mitochondrial redox state of biventricular working hearts during protocols that alter the rate of myocyte metabolism or induce hypoxia or create a combination of the two. Hearts from New Zealand white rabbits were connected to a biventricular working heart system (Hugo Sachs Elektronik) and perfused with modified Krebs-Henseleit solution16 at 37 °C. Aortic, LV, pulmonary artery, and left & right atrial pressures were recorded. Electrical activity was measured using a monophasic action potential electrode. To image fNADH, light from a mercury lamp was filtered (350±25 nm) and used to illuminate the epicardium. Emitted light was filtered (460±20 nm) and imaged using a CCD camera. Changes in the epicardial fNADH of biventricular working hearts during different pacing rates are presented. The combination of the heart model and fNADH imaging provides a new and valuable experimental tool for studying acute cardiac pathologies within the context of realistic physiological conditions.

NADH Fluorescence Imaging of Isolated Biventricular Working Rabbit Hearts

Since its inception by Langendorff1, the isolated perfused heart remains a prominent tool for studying cardiac physiology2. However, it is not well-suited for studies of cardiac metabolism, which require the heart to perform work within the context of physiologic preload and afterload pressures. Neely introduced modifications to the Langendorff technique to establish appropriate left ventricular (LV) preload and afterload pressures3. The model is known as the isolated LV working heart model and has been used extensively to study LV performance and metabolism4-6. This model, however, does not provide a properly loaded right ventricle (RV). Demmy et al. first reported a biventricular model as a modification of the LV working heart model7, 8. They found that stroke volume, cardiac output, and pressure development improved in hearts converted from working LV mode to biventricular working mode8. A properly loaded RV also diminishes abnormal pressure gradients across the septum to improve septal function. Biventricular working hearts have been shown to maintain aortic output, pulmonary flow, mean aortic pressure, heart rate, and myocardial ATP levels for up to 3 hours8.When studying the metabolic effects of myocardial injury, such as ischemia, it is often necessary to identify the location of the affected tissue. This can be done by imaging the fluorescence of NADH (the reduced form of nicotinamide adenine dinucleotide)9-11, a coenzyme found in large quantities in the mitochondria. NADH fluorescence (fNADH) displays a near linearly inverse relationship with local oxygen concentration12 and provides a measure of mitochondrial redox state13. fNADH imaging during hypoxic and ischemic conditions has been used as a dye-free method to identify hypoxic regions14, 15 and to monitor the progression of hypoxic conditions over time10.The objective of the method is to monitor the mitochondrial redox state of biventricular working hearts during protocols that alter the rate of myocyte metabolism or induce hypoxia or create a combination of the two. Hearts from New Zealand white rabbits were connected to a biventricular working heart system (Hugo Sachs Elektronik) and perfused with modified Krebs-Henseleit solution16 at 37 °C. Aortic, LV, pulmonary artery, and left & right atrial pressures were recorded. Electrical activity was measured using a monophasic action potential electrode. To image fNADH, light from a mercury lamp was filtered (350±25 nm) and used to illuminate the epicardium. Emitted light was filtered (460±20 nm) and imaged using a CCD camera. Changes in the epicardial fNADH of biventricular working hearts during different pacing rates are presented. The combination of the heart model and fNADH imaging provides a new and valuable experimental tool for studying acute cardiac pathologies within the context of realistic physiological conditions.

The onion skin-like organization of the septum arises from multiple embryonic origins to form multiple adult neuronal fates

In the past several decades, tremendous progress has been achieved through developmental studies of the central nervous system structures such as the cerebral cortex. The septum, which receives reciprocal connections from a variety of brain structures, contains diverse projection neurons but few interneurons. However, the mechanisms underlying its development remain poorly understood. Here we show that the septum is organized into an onion skin-like structure composed of five groups of neurons. These neurons are parvalbumin, choline acetyltransferase, neuronal nitric oxide synthase, calretinin and calbindin immunoreactive. Using the BrdU birth-dating method, we found that these five groups of neurons in the septum are grossly generated following an outside-in pattern. Interestingly, the distinct molecular identities of these neuronal subtypes correspond to their heterogeneous subpallial origins. Using three specific transgenic mouse lines and focal in utero electroporation of Cre-reporter plasmid, we showed that septal neurons originate from not only local progenitor regions but also neighboring progenitor regions including the medial ganglionic eminence and preoptic area. Thus, the neuronal diversity of the septum is achieved through both temporal and spatial control. Our results also suggest that multiple neuronal subtypes arrive to the septum through both radial and tangential migration. Based on these findings, we proposed a novel developmental model involving multiple spatial–temporal origins of septal neurons. This study presents new perspectives for comprehensively exploring septal functions in brain circuits.

Regional Left Ventricular Systolic Function and the Right Ventricle: The Multi-Ethnic Study of Atherosclerosis Right Ventricle Study

Dysfunction of the interventricular septum has been implicated in right ventricular (RV) failure. However, little is known about the relationship between ventricular septal and RV function in patients without clinical cardiovascular disease. We hypothesized that better septal function would be associated with higher RV ejection fraction and lower RV mass and volume by cardiac MRI.In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac MRI was performed on community-based participants without clinical cardiovascular disease. Images were analyzed by the harmonic phase method to measure peak circumferential systolic midventricular strain for each wall (anterior, lateral, inferior, and septal). Multivariable linear regression and generalized additive models were used to assess the relationship between septal strain and RV morphology.There were 917 participants (45.7% women) with a mean age of 65.7 years. Better septal function was associated with higher RV ejection fraction in a nonlinear fashion after adjustment for all covariates (P = .03). There appeared to be a threshold effect for the contribution of septal strain to RV systolic function, with an almost linear decrement in RV ejection fraction with septal strain from -18% to -10%. Septal function was not related to RV mass or volume.Interventricular septal function was linked to RV systolic function independent of other left ventricular regions, even in individuals without clinical cardiovascular disease. This finding confirms animal and human research suggesting the importance of septal function to the right ventricle and implies that changes in septal function could herald RV dysfunction.ClinicalTrials.gov; No.: NCT00005487; URL: www.clinicaltrials.gov.

Early Changes in Left Ventricular Long-Axis Function in Friedreich Ataxia: Relation with the FXN Gene Mutation and Cardiac Structural Change

Friedreich ataxia (FRDA) is an autosomal recessive condition due to a GAA triplet expansion in the FXN gene that causes increased left ventricular (LV) wall thickness and can progress to LV systolic dysfunction. However, the changes in myocardial function that occur before a reduction in LV ejection fraction are incompletely understood. LV long-axis function was assessed by measurement of tissue Doppler imaging (TDI) peak systolic (S`), early diastolic (E`), and atrial velocities (A`) at the septal and lateral borders of the mitral annulus in 60 subjects homozygous for a GAA expansion in the FXN gene who had preserved LV ejection fraction. Comparison was made with 60 sex- and age-matched controls. TDI velocities at 5 years were compared with baseline values in 17 FRDA subjects with follow-up studies who still had preserved ejection fraction. S` and E` were reduced in FRDA subjects at both the septal and the lateral mitral annular borders. Lateral E` was independently and inversely related to age, blood pressure, septal wall thickness, and the number of GAA repeats in the smaller allele of the FXN gene, whereas septal E` was not correlated with GAA repeat number. At 5 years, there was a reduction in lateral S` and E` but no change in septal TDI velocities. Subjects with FRDA have impairment of septal and lateral long-axis LV function, but there also seem to be regional differences in the effects of this condition that are at least partly related to the degree of genetic abnormality.

Tetralogy of Fallot: Impact of the Excursion of the Interventricular Septum on Left Ventricular Systolic Function and Fibrosis after Surgical Repair

To quantify the excursion of interventricular septum (IVS) in patients after repair of tetralogy of Fallot (TOF), a marker of interventricular interaction, and assess its association with left ventricular (LV) ejection fraction, LV septal wall thickening, and LV fibrosis. The HIPAA-compliant protocol received institutional board review approval. IVS excursion was measured at cardiovascular magnetic resonance (MR) imaging in 82 patients after repair of TOF and in 10 healthy volunteers. IVS excursion was correlated with LV ejection fraction, LV septal wall thickening, and LV delayed gadolinium enhancement. Independent predictors of reduced LV ejection fraction were identified, including significant univariable predictors with use of a multivariable logistic regression model. IVS excursion was greater in patients than in healthy volunteers (5.3 mm ± 3.1 vs 1.2 mm ± 0.4, P < .01). Patients (n = 68) with abnormal excursion of the IVS had reduced LV ejection fraction (57% ± 7 vs 61% ± 4, P < .01) and reduced LV septal wall thickening (24% ± 10 vs 29% ± 5, P = .01) compared with patients with normal IVS excursion. Maximal IVS excursion (odds ratio = 1.27 per millimeter, P = .03) and right ventricular (RV) ejection fraction (odds ratio = 0.92 per percentage, P = .031) were independent predictors of reduced LV ejection fraction (<55%). Among the 44 patients with delayed enhancement images, those with abnormal excursion of the IVS had higher LV delayed enhancement scores (median, 1.5 [interquartile range, 0-2] vs 0 [interquartile range, 0-0]; P < .01] than patients with normal IVS excursion. Notably, in all but one patient the delayed enhancement was located at the RV-LV hinge points. Abnormal IVS excursion after repair of TOF is associated with reduced global and septal LV systolic function and LV fibrosis at the RV-LV hinge points, suggesting a mechanism of adverse interventricular interaction.

Effect of pericardial repair after aortic valve replacement on septal and right ventricular function

BackgroundAortic valve replacement (AVR) is associated with reversed septal motion and right ventricular (RV) dysfunction but the cause remains uncertain. The aim of this study was to investigate the role of pericardial repair after AVR on septal and RV function. MethodsThirty patients (62±11years, 18 males) with severe aortic stenosis were studied before and after AVR surgery using echocardiography. Patients were randomly allocated to pericardial repair vs. open pericardium. RV long axis displacement and outflow tract fractional shortening (fs) were measured. RV and right atrial (RA) tissue Doppler and strain rate (SR) were measured as well as RA area. Systolic interventricular septal motion towards and away from the RV was also determined. Stroke volume (SV) was measured by conventional Doppler method. Pre-operative data were compared with those from 30 normal gender and age matched controls. ResultsPost-operatively, global RV ejection function was preserved as shown by SV. However, RV outflow tract fs and long axis displacement both fell (p<0.01) but not SR. RA area remained unchanged but RA SR fell (p<0.01). RV displacement correlated with the extent of reversed septal motion (r=0.60, p<0.001) as well as RA SR (r=0.54, p<0.001). None of the RV or septal measurements was affected by the pericardial repair procedure. ConclusionAfter AVR, septal motion is reversed and correlated directly with RV long axis function. The latter is not affected by pericardial repair but likely related to right atrial surgery injury.

Septal rebound stretch reflects the functional substrate to cardiac resynchronization therapy and predicts volumetric and neurohormonal response

To develop a novel myocardial deformation index that is highly sensitive to the effect of cardiac resynchronization therapy (CRT) and that can be used to predict response to CRT. Before and 6.5 +/- 2.3 months after implantation of a CRT device, longitudinal shortening and stretch were timed and quantified by speckle tracking echocardiography in a cohort of 62 patients. Distinction was made between systolic total stretch (STS; all systolic stretch) and systolic rebound stretch (SRS; only systolic stretch following initial shortening). Systolic total stretch and SRS could be measured in all wall segments in 41 of 62 patients. Septal SRS quantification was possible in all 62 patients and was performed by a blinded observer. Cardiac resynchronization therapy reduced STS (-55 +/- 30%) but reduced SRS (-77 +/- 21%) significantly more (P < 0.01). The largest amount of baseline SRS and the largest reductions in SRS (-90 +/- 22%) were found in the septum. Reductions in local SRS were paralleled by increases in local systolic shortening that were twice as large (r = 0.79), thereby strongly improving septal function. Baseline values of septal SRS correlated with reductions in left ventricular end-systolic volume index (Delta LVESVi; r = 0.62) and brain-type natriuretic peptide (BNP) (Delta log(10)BNP; r = 0.57). Septal SRS was an independent predictor of CRT response in linear regression analysis and predicted Delta LVESVi of >or=15% with a sensitivity and specificity of 81% at ROC analysis (areas under the curve 0.89 +/- 0.04). Septal rebound stretch appears to be a sensitive and practical diagnostic criterion to quantify the functional substrate amenable to CRT and to predict response.

Effect of Transcatheter Pulmonary Valve Implantation on Short-Term Right Ventricular Function as Determined by Two-Dimensional Speckle Tracking Strain and Strain Rate Imaging

Transcatheter pulmonary valve implantation (PVI) is an emerging therapy for right ventricular (RV) outflow dysfunction in congenital heart disease. We investigated, for the first time in children after surgery for congenital heart disease, the short-term effects of PVI on RV and left ventricular (LV) function using 2-dimensional speckle tracking echocardiography and tissue Doppler imaging. We hypothesized that the short-term RV and LV function would improve. Two-dimensional speckle tracking echocardiograms and pulsed tissue Doppler images were obtained before and 1 to 2 days after PVI (18-mm Melody valve). The catheter right heart hemodynamics were recorded. The strain and strain rate of the basal lateral left ventricle, lateral right ventricle, and interventricular septum were measured by 2-dimensional speckle tracking echo, and the pre- and postprocedure values were compared. Of the 16 eligible patients (age 16 +/- 2 years), the scans of 10 had correct image format and adequate quality. PVI was performed for volume (n = 4) or combined pressure-volume (n = 6) loading. After PVI, the RV to pulmonary artery pressure gradient (33 +/- 22 to 12 +/- 4 mm Hg, p = 0.02), pulmonary regurgitation, and RV end-diastolic volume (3.2 +/- 0.8 to 2.8 +/- 0.6 cm, p = 0.02) decreased, and the septal systolic velocities (3.5 +/- 1.1 to 4.7 +/- 1.1 cm/s, p = 0.04), strain (-7.6 +/- 9.3% to -15.6% +/- 6.7%, p = 0.01) and strain rate (-0.3 +/- 1.1 to -1.1 +/- 0.5 1/s, p = 0.04) and RV free wall strain increased (-17.4 +/- 8.6% to -23.4% +/- 6.2%, p = 0.03). The LV tissue velocities, strain, and strain rate were unchanged. In conclusion, PVI leads to RV unloading and acutely improves RV and septal function.

Right Ventricular Failure Resulting from Pressure Overload: Role of Intra-Aortic Balloon Counterpulsation and Vasopressor Therapy

Augmentation of coronary perfusion may improve right ventricular (RV) failure following acute increases of RV afterload. We investigated whether intra-aortic balloon counterpulsation (IABP) can improve cardiac function by enhancing myocardial perfusion and reversing compromised biventricular interactions using a model of acute pressure overload. In 10 anesthetized pigs, RV failure was induced by pulmonary artery constriction and systemic hypertension strategies with IABP, phenylephrine (PE), or the combination of both were tested. Systemic and ventricular hemodynamics [cardiac index(CI), ventricular pressures, coronary driving pressures (CDP)] were measured and echocardiography was used to assess tricuspid valve regurgitation, septal positioning (eccentricity index (ECI)), and changes in ventricular and septal dimensions and function [myocardial performance index (MPI), peak longitudinal strain]. Pulmonary artery constriction resulted in doubling of RV systolic pressure (54 ± 4mm Hg), RV distension, severe TR (4+) with decreased RV function (strain: -33%; MPI: +56%), septal flattening (Wt%: -35%) and leftward septal shift (ECI:1.36), resulting in global hemodynamic deterioration (CI: -51%; SvO(2): -26%), and impaired CDP (-30%; P<0.05). IABP support alone failed to improve RV function despite higher CDP (+33%; P<0.05). Systemic hypertension by PE improved CDP (+70%), RV function (strain: +22%; MPI: -21%), septal positioning (ECI:1.12) and minimized TR, but LV dysfunction (strain: -25%; MPI: +31%) occurred after LV afterloading (P<0.05). With IABP, less PE (-41%) was needed to maintain hypertension and CDP was further augmented (+25%). IABP resulted in LV unloading and restored LV function, and increased CI (+46%) and SvO(2) (+29%; P<0.05). IABP with minimal vasopressors augments myocardial perfusion pressure and optimizes RV function after pressure-induced failure.