Impaired distensibility of the left ventricle after stiffening of the right ventricle.

Acute and chronic alterations of right ventricular (RV) wall properties can change left ventricular (LV) performance. We investigated whether and how stiffening of the RV free wall alters LV diastolic distensibility. We used cross-circulated isolated hearts, in which the LV and RV were independently controllable. Stiffness of the RV free wall was altered by intramuscular injections of glutaraldehyde into the RV free wall after right coronary artery ligation. We measured circumferential and longitudinal regional lengths in the septum and LV free wall. During data acquisition, RV volume was held constant. After the RV free wall was stiffened by glutaraldehyde, the LV diastolic pressure-volume relation shifted upward and became steeper. Importantly, stiffening of the RV free wall increased the diastolic regional area in the septum and LV free wall under constant LV volume. The augmented regional dimensions may result in enhanced regional tension under constant LV volume and may be related to the observed increase in LV diastolic intracavitary pressure. The impaired LV diastolic distensibility by stiffening of the RV free wall may be at least partly explained by myocardial stretch, probably due to LV deformation.     

A 2D FE model of the heart demonstrates the role of the pericardium in ventricular deformation

During pulmonary artery constriction (PAC), an experimental model of acute right ventricular (RV) pressure overload, the interventricular septum flattens and inverts. Finite element (FE) analysis has shown that the septum is subject to axial compression and bending when so deformed. This study examines the effects of acute PAC on the left ventricular (LV) free wall and the role the pericardium may play in these effects. In eight open-chest anesthetized dogs, LV, RV, aortic, and pericardial pressures were recorded under control conditions and with PAC. Model dimensions were derived from two-dimensional echocardiography minor-axis images of the heart. At control (pericardium closed), FE analysis showed that the septum was concave to the LV; stresses in the LV, RV, and septum were low; and the pericardium was subject to circumferential tension. With PAC, RV end-diastolic pressure exceeded LV pressure and the septum inverted. Compressive stresses developed circumferentially in the septum out to the RV insertion points, forming an arch-like pattern. Sharp bending occurred near the insertion points, accompanied by flattening of the LV free wall. With the pericardium open, the deformations and stresses were different. The RV became much larger, especially with PAC. With PAC, the arch-like circumferential stresses still developed in the septum, but their magnitudes were reduced, compared with the pericardium-closed case. There was no free wall inversion and flattening was less. From these FE results, the pericardium has a significant influence on the structural behavior of the septum and the LV and RV free walls. Furthermore, the deformation of the heart is dependent on whether the pericardium is open or closed.     

Radiofrequency ablation of premature ventricular contractions originating from uncommon sites of right ventricle

Premature Ventricular Contraction (PVC)/ventricular tachycardia (VT) with left bundle branch block (LBBB) morphology and inferior axis has been described classically to originate from the right ventricular outflow tract (RVOT). Some uncommon sites of idiopathic ventricular arrhythmia (VA) origins have been revealed including tricuspid annulus (TA) and right ventricular (RV) inflow free wall region. We present a series of two cases who have undergone electrophysiological study and successful radiofrequency ablation of frequent monomorphic PVCs with LBBB pattern originating from relatively uncommon sites of RV – TA and RV inflow free wall region.     

Compression induced by RV pressure overload decreases regional coronary blood flow in anesthetized dogs

Pulmonary artery constriction (PAC), a model of right ventricular (RV) pressure overload, flattens or inverts the septum and may flatten the left ventricular (LV) free wall. Finite element (FE) analysis predicts that such deformations may cause substantial compression. This study tests the hypothesis that deformation-induced myocardial compressive stress impedes coronary blood flow (CBF). Colored microspheres ( approximately 2 x 10(6)) were injected into the left atrium of 13 open-chest, anesthetized dogs under control conditions and during PAC, which decreased the end-diastolic transseptal pressure gradient (LV - RV) from 1.6 +/- 1.3 to -3.4 +/- 1.7 mmHg. Septal and LV deformation was assessed with the use of two-dimensional echocardiography, and by FE analysis, the hydrostatic component of stress was assessed. Postmortem, a 2.5-cm wide, LV equatorial ring was divided into 16 endocardial and epicardial samples. PAC decreased CBF in the FE-predicted compression zones, areas with the greatest compression having the greatest reductions in CBF. During PAC, compression reached a maximum of 25.3 +/- 1.8 mmHg on the (LV) endocardial sides of the RV insertion points, areas that saw CBF decrease from 1.05 +/- 0.08 to 0.68 +/- 0.05 ml.min(-1).g(-1) (P < 0.001), more than 30%. CBF decreased (from 1.08 +/- 0.07 to 0.81 +/- 0.07 ml.min(-1).g(-1); P < 0.001) on the RV side of the midseptum, an area with as much as 16.0 +/- 1.0 mmHg of compression. Overall, average compressions of 10 mmHg decreased CBF by approximately 30%. We conclude that acute RV pressure overload deforms the septum and LV and induces compressive stresses that reduce CBF substantially. This may help explain why some patients with pulmonary hypertension and no critical coronary disease have chest discomfort indistinguishable from angina pectoris.     

Right and left ventricular adaptation to hypoxia: a tissue Doppler imaging study

Hypoxia has been reported to alter left ventricular (LV) diastolic function, but associated changes in right ventricular (RV) systolic and diastolic function remain incompletely documented. We used echocardiography and tissue Doppler imaging to investigate the effects on RV and LV function of 90 min of hypoxic breathing (fraction of inspired O(2) of 0.12) compared with those of dobutamine to reproduce the same heart rate effects without change in pulmonary vascular tone in 25 healthy volunteers. Hypoxia and dobutamine increased cardiac output and tricuspid regurgitation velocity. Hypoxia and dobutamine increased LV ejection fraction, isovolumic contraction wave velocity (ICV), acceleration (ICA), and systolic ejection wave velocity (S) at the mitral annulus, indicating increased LV systolic function. Dobutamine had similar effects on RV indexes of systolic function. Hypoxia did not change RV area shortening fraction, tricuspid annular plane systolic excursion, ICV, ICA, and S at the tricuspid annulus. Regional longitudinal wall motion analysis revealed that S, systolic strain, and strain rate were not affected by hypoxia and increased by dobutamine on the RV free wall and interventricular septum but increased by both dobutamine and hypoxia on the LV lateral wall. Hypoxia increased the isovolumic relaxation time related to RR interval (IRT/RR) at both annuli, delayed the onset of the E wave at the tricuspid annulus, and decreased the mitral and tricuspid inflow and annuli E/A ratio. We conclude that hypoxia in normal subjects is associated with altered diastolic function of both ventricles, improved LV systolic function, and preserved RV systolic function.     

Heterogeneous connexin43 expression produces electrophysiological heterogeneities across ventricular wall

Recently we found that electrophysiological (EP) heterogeneities between subepicardial and midmyocardial cells can form a substrate for reentrant ventricular arrhythmias. However, cell-to-cell coupling through gap junctions is expected to attenuate transmural heterogeneities between cell types spanning the ventricular wall. Because connexin43 (Cx43) is the principal ventricular gap junction protein, we hypothesized that transmural EP heterogeneities are in part produced by heterogeneous Cx43 expression across the ventricular wall. The left ventricles of eight dogs were sectioned to expose the transmural surface. To determine whether heterogeneous Cx43 expression influenced EP function, high-resolution transmural optical mapping of the arterially perfused canine wedge preparation was used to measure transmural conduction velocity (thetaTM), dV/dt(max), transmural space constant (lambdaTM), and transmural gradients of action potential duration (APD). Relative Cx43 expression, quantified by confocal immunofluorescence, was significantly lower (by 24 +/- 17%; P < 0.05) in subepicardial compared with deeper layers. Importantly, reduced subepicardial Cx43 was associated with transmural heterogeneities of EP function evidenced by selectively reduced subepicardial thetaTM (by 18 +/- 9%; P < 0.05) compared with deeper layers. In subepicardial regions, dV/dt(max) was fastest (by 19 +/- 15%) and lambdaTM was smallest (by 18.1 +/- 2%), which suggests that conduction slowing was attributable to localized uncoupling rather than reduced excitability. The maximum transmural APD gradients occurred in the same regions where Cx43 expression was lowest; this suggests that Cx43 expression patterns served to maintain APD gradients across the transmural wall. These data demonstrate that heterogeneous Cx43 expression is closely associated with functionally significant EP heterogeneities across the transmural wall. Therefore, Cx43 expression patterns can potentially contribute to arrhythmic substrates that are dependent on transmural electrophysiological heterogeneities.     

Premature ventricular contractions of the right ventricular outflow tract: is there an incipient underlying disease? New insights from a speckle tracking echocardiography study

ContextPremature ventricular contractions (PVCs) originating in the right ventricular outflow tract (RVOT) are traditionally considered idiopathic and benign. Echocardiographic conventional measurements are typically normal.AimsTo assess whether right ventricle longitudinal strain, determined by two-dimensional speckle tracking echocardiography, differ between RVOT PVCs patients (treated with catheter ablation) and healthy controls.MethodsWe retrospectively selected patients with PVCs from the RVOT who underwent electrophysiological study and catheter ablation between 2016 and 2019. Patients with documented structural heart disease were excluded. Transthoracic echocardiography was performed and right ventricle global longitudinal strain (RV-GLS), free wall longitudinal strain (RVFW-LS) and left ventricle global longitudinal strain (LV-GLS) were determined as well as conventional ultrasound measurements of RV and LV function.ResultsWe studied 21 patients with RVOT PVCs and 13 controls. Patients with PVCs from the RVOT had lower values of RV-GLS and RVFW-LS compared with the control group (?19.4% versus ?22.5%, P = 0.015 and ?22.1% versus ?25.5, P = 0.041, respectively). They also had lower values of LV-GLS, although still within the normal range (?19.1% versus ?20.9%, P = 0.047). Regarding RVOT PVCs patients only, RV-GLS and RVFW-LS had no correlation with the PVCs burden prior to catheter ablation and they did not differ between the patients in whom the catheter ablation was successful and those in whom it was not. RV-GLS also had a positive correlation with RVOT proximal diameter (r = 0.487, P = 0.025).ConclusionsIn this group of RVOT PVCs patients, we found worse RV longitudinal strain values (and therefore sub-clinical myocardial dysfunction) when compared to healthy controls.     

Altered expression of connexin43 contributes to the arrhythmogenic substrate during the development of heart failure in cardiomyopathic hamster

Heart failure is known to predispose to life-threatening ventricular tachyarrhythmias even before compromising the systemic circulation, but the underlying mechanism is not well understood. The aim of this study was to clarify the connexin43 (Cx43) gap junction remodeling and its potential role in the pathogenesis of arrhythmias during the development of heart failure. We investigated stage-dependent changes in Cx43 expression in UM-X7.1 cardiomyopathic hamster hearts and associated alterations in the electrophysiological properties using a high-resolution optical mapping system. UM-X7.1 hamsters developed left ventricular (LV) hypertrophy by ages 6 approximately 10 wk and showed a moderate reduction in LV contractility at age 20 wk. Appreciable interstitial fibrosis was recognized at these stages. LV mRNA and protein levels of Cx43 in UM-X7.1 were unaffected at age 10 wk but significantly reduced at 20 wk. The expression level of Ser255-phosphorylated Cx43 in UM-X7.1 at age 20 wk was significantly greater than that in control golden hamsters at the same age. In UM-X7.1 at age 10 wk, almost normal LV conduction was preserved, whereas the dispersion of action potential duration was significantly increased. UM-X7.1 at age 20 wk showed significant reduction of cardiac space constant, significant decrease in conduction velocity, marked distortion of activation fronts, and pronounced increase in action potential duration dispersion. Programmed stimulation resulted in sustained ventricular tachycardia or fibrillation in UM-X7.1. LV activation during polymorphic ventricular tachycardia was characterized by multiple phase singularities or wavebreaks. During the development of heart failure in the cardiomyopathic hamster, alterations of Cx43 expression and phosphorylation in concert with interstitial fibrosis may create serious arrhythmogenic substrate through an inhibition of cell-to-cell coupling.     

Left ventricular effects on right ventricular developed pressure.

The possibility that left ventricular (LV) performance might affect right ventricular (RV) function through the myocardium was examined by using isolated, flow-perfused, paced rabbit hearts beating isovolumically. Reducing LV volume from its optimal volume to zero caused a 5.7% decrease (N = 10, P less than 0.001) in right ventricular developed pressure (RVDP). Ligating the anterior ventricular branches of the left coronary artery which in the rabbit supply the LV free wall resulted in an additional 9.3% decrease in RVDP (N = 5, P = 0.05) within 3 min of ligation. Finally, cutting the LV free wall from the atrioventricular orifice to the apex (thereby preventing any developed LV free wall force during systole) caused a 45% further decrease in RVDP (N = 2, P less than 0.02). Cineradiographic study showed that the alterations in RVDP resulting from changes in LV volume and coronary occlusion correlated significantly (N = 5, P less than 0.01) with the magnitude of septal bulging into the RV cavity during systole. The results indicate that alteration in LV free wall function and changes in LV volume can directly effect RVDP through the myocardium.     

Opening the pericardium during pulmonary artery constriction improves cardiac function.

During acute pulmonary hypertension, both the pericardium and the right ventricle (RV) constrain left ventricular (LV) filling; therefore, pericardiotomy should improve LV function. LV, RV, and pericardial pressures and RV and LV dimensions and LV stroke volume (SV) were measured in six anesthetized dogs. The pericardium was closed, the chest was left open, and the lungs were held away from the heart. Data were collected at baseline, during pulmonary artery constriction (PAC), and after pericardiotomy with PAC maintained. PAC decreased SV by one-half. RV diameter increased, and septum-to-LV free wall diameter and LV area (our index of LV end-diastolic volume) decreased. Compared with during PAC, pericardiotomy increased LV area and SV increased 35%. LV and RV compliance (pressure-dimension relations) and LV contractility (stroke work-LV area relations) were unchanged. Although series interaction accounts for much of the decreased cardiac output during acute pulmonary hypertension, pericardial constraint and leftward septal shift are also important. Pericardiotomy can improve LV function in the absence of other sources of external constraint to LV filling.     

Tbx5 specifies the left/right ventricles and ventricular septum position during cardiogenesis

Extensive misexpression studies were carried out to explore the roles played by Tbx5, the expression of which is excluded from the right ventricle (RV) during cardiogenesis. When Tbx5 was misexpressed ubiquitously, ventricular septum was not formed, resulting in a single ventricle. In such heart, left ventricle (LV)-specific ANF gene was induced. In search of the putative RV factor(s), we have found that chick Tbx20 is expressed in the RV, showing a complementary fashion to Tbx5. In the Tbx5-misexpressed heart, this gene was repressed. When misexpression was spatially partial, leaving small Tbx5-negative area in the right ventricle, ventricular septum was shifted rightwards, resulting in a small RV with an enlarged LV. Focal expression induced an ectopic boundary of Tbx5-positive and -negative regions in the right ventricle, at which an additional septum was formed. Similar results were obtained from the transient transgenic mice. In such hearts, expression patterns of dHAND and eHAND were changed with definitive cardiac abnormalities. Furthermore, we report that human ANF promoter is synergistically activated by Tbx5, Nkx2.5 and GATA4. This activation was abrogated by Tbx20, implicating the pivotal roles of interactions among these heart-specific factors. Taken together, our data indicate that Tbx5 specifies the identity of LV through tight interactions among several heart-specific factors, and highlight the essential roles of Tbx5 in cardiac development.     

The impact of endurance exercise training on left ventricular systolic mechanics

Although exercise training-induced changes in left ventricular (LV) structure are well characterized, adaptive functional changes are incompletely understood. Detailed echocardiographic assessment of LV systolic function was performed on 20 competitive rowers (10 males and 10 females) before and after endurance exercise training (EET; 90 days, 10.7 +/- 1.1 h/wk). Structural changes included LV dilation (end-diastolic volume = 128 +/- 25 vs. 144 +/- 28 ml, P < 0.001), right ventricular (RV) dilation (end-diastolic area = 2,850 +/- 550 vs. 3,260 +/- 530 mm2, P < 0.001), and LV hypertrophy (mass = 227 +/- 51 vs. 256 +/- 56 g, P < 0.001). Although LV ejection fraction was unchanged (62 +/- 3% vs. 60 +/- 3%, P = not significant), all direct measures of LV systolic function were altered. Peak systolic tissue velocities increased significantly (basal lateral S'Delta = 0.9 +/- 0.6 cm/s, P = 0.004; and basal septal S'Delta = 0.8 +/- 0.4 cm/s, P = 0.008). Radial strain increased similarly in all segments, whereas longitudinal strain increased with a base-to-apex gradient. In contrast, circumferential strain (CS) increased in the LV free wall but decreased in regions adjacent to the RV. Reductions in septal CS correlated strongly with changes in RV structure (DeltaRV end-diastolic area vs. DeltaLV septal CS; r2 = 0.898, P < 0.001) and function (Deltapeak RV systolic velocity vs. DeltaLV septal CS, r2 = 0.697, P < 0.001). EET leads to significant changes in LV systolic function with regional heterogeneity that may be secondary to concomitant RV adaptation. These changes are not detected by conventional measurements such as ejection fraction.     

Differences in the pattern of ventricular activation in small rodents determined by morphological organization of the cardiac ventricular conduction system

Ventricular activation of the mouse heart differs significantly compared to activation in larger mammals. Knowledge of structural and functional characteristics of laboratory animals is essential for evaluation of results obtained from experiments. The present study was performed to evaluate whether the different pattern of activation is common to small rodents or unique for mice. Hearts of adult Wistar rats were isolated and Langendorff perfused. After removing the right and left ventricular free wall, extracellular activity of the septum and bundle branches (BB) was determined using a multi-terminal electrode harboring 247 terminals. Immunolabeling on cryosections was performed to assess expression and distribution of the gap junction proteins Connexin40 (Cx40), Cx43, Cx45, contractile (Desmin, alpha-actinin) and intercalated disk-related (N-cadherin, beta-catenin) proteins. Collagen distribution was assessed by Sirius Red staining. Reconstruction of the left and right bundle branch (LBB and RBB) using immuno-labeling revealed that the LBB spreads all over the septal surface. The RBB too is broad, albeit to a lesser extend than LBB. A sheet of connective tissue electrically separates the common bundle and proximal BB from the septal working myocardium. Immunolabeling revealed clear differences between the conduction system and the working myocardium with respect to expression level and distribution of the different proteins analyzed. The morphological organization of the area resulted in an electrical activation pattern of the septum comparable to what is common in larger mammals: earliest activation at the midseptum via the bundle branches. From our data we conclude that the pattern of ventricular activation in the rat heart and the structure of the conduction system fit to data described for larger mammals and differ from the different pattern previously found in mouse heart.     

Differential effects of left ventricular pacing sites in an acute canine model of contraction dyssynchrony

The goal of the present study was to assess the effects of left ventricular (LV) pacing sites (apex vs. free wall) on radial synchrony and global LV performance in a canine model of contraction dyssynchrony. Ultrasound tissue Doppler imaging and hemodynamic (LV pressure-volume) data were collected in seven anesthetized, opened-chest dogs. Right atrial (RA) pacing served as the control, and contraction dyssynchrony was created by simultaneous RA and right ventricular (RV) pacing to induce a left bundle-branch block-like contraction pattern. Cardiac resynchronization therapy (CRT) was implemented by adding simultaneous LV pacing to the RV pacing mode at either the LV apex (CRTa) or free wall (CRTf). A new index of synchrony was developed via pair-wise cross-correlation analysis of tissue Doppler radial strain from six midmyocardial cross-sectional regions, with a value of 15 indicating perfect synchrony. Compared with RA pacing, RV pacing significantly decreased radial synchrony (11.1 +/- 0.8 vs. 4.8 +/- 1.2, P < 0.01) and global LV performance (cardiac output: 2.0 +/- 0.3 vs. 1.4 +/- 0.1 l/min and stroke work: 137 +/- 22 vs. 60 +/- 14 mJ, P < 0.05). Although both CRTa and CRTf significantly improved radial synchrony, only CRTa markedly improved global function (cardiac output: 2.1 +/- 0.2 l/min and stroke work: 113 +/- 13 mJ, P < 0.01 vs. RV pacing). Furthermore, CRTa decreased LV end-systolic volume compared with RV pacing without any change in LV end-systolic pressure, indicating an augmented global LV contractile state. Thus, LV apical pacing appears to be a superior pacing site in the context of CRT. The dissociation between changes in synchrony and global LV performance with CRTf suggests that regional analysis from a single plane may not be sufficient to adequately characterize contraction synchrony.     

Residual Cx45 and its relationship to Cx43 in murine ventricular myocardium

Gap junction channels in ventricular myocardium are required for electrical and metabolic coupling between cardiac myocytes and for normal cardiac pump function. Although much is known about expression patterns and remodeling of cardiac connexin(Cx)43, little is known about the less abundant Cx45, which is required for embryonic development and viability, is downregulated in adult hearts, and is pathophysiologically upregulated in human end-stage heart failure. We applied quantitative immunoblotting and immunoprecipitation to native myocardial extracts, immunogold electron microscopy to cardiac tissue and membrane sections, electrophysiological recordings to whole hearts, and high-resolution tandem mass spectrometry to Cx45 fusion protein, and developed two new tools, anti-Cx45 antisera and Cre+;Cx45 floxed mice, to facilitate characterization of Cx45 in adult mammalian hearts. We found that Cx45 represents 0.3% of total Cx protein (predominantly 200 fmol Cx43 protein/μg ventricular protein) and colocalizes with Cx43 in native ventricular gap junctions, particularly in the apex and septum. Cre+;Cx45 floxed mice express 85% less Cx45, but do not exhibit overt electrophysiologic abnormalities. Although the basal phosphorylation status of native Cx45 remains unknown, CaMKII phosphorylates 8 Ser/Thr residues in Cx45 in vitro. Thus, although downregulation of Cx45 does not produce notable deficits in electrical conduction in adult, disease-free hearts, Cx45 is a target of the multifunctional kinase CaMKII, and the phosphorylation status of Cx45 and the role of Cx43/Cx45 heteromeric gap junction channels in both normal and diseased hearts merits further investigation.     

Expression of gap junction protein connexin43 in the adult rat cochlea: comparison with connexin26.

To elucidate whether the two different gap junction proteins connexin43 (Cx43) and connexin26 (Cx26) are expressed and localized in a similar manner in the adult rat cochlea, we performed three-dimensional confocal microscopy using cryosections and surface preparations. In the cochlear lateral wall, Cx43-positive spots were localized mainly in the stria vascularis and only a few spots were present in the spiral ligament, whereas Cx26-positive spots were detected in both the stria vascularis and the spiral ligament. In the spiral limbus, Cx43 was widely distributed, whereas Cx26 was more concentrated on the side facing the scala vestibuli and in the basal portion. In the organ of Corti, Cx43-positive spots were present between the supporting cells but they were fewer and much smaller than those of Cx26. These data demonstrated distinct differences between Cx43 and Cx26 in expression and localization in the cochlea. In addition, the area of overlap of zonula occludens-1 (ZO-1) immunolabeling with Cx43-positive spots was small, whereas it was fairly large with Cx26-positive spots in the cochlear lateral wall, suggesting that the differences are not associated with the structural difference between carboxyl terminals, i.e., those of Cx43 possess sequences for binding to ZO-1, whereas those of Cx26 lack these binding sequences.     

Residual Cx45 and its relationship to Cx43 in murine ventricular myocardium

Gap junction channels in ventricular myocardium are required for electrical and metabolic coupling between cardiac myocytes and for normal cardiac pump function. Although much is known about expression patterns and remodeling of cardiac connexin(Cx)43, little is known about the less abundant Cx45, which is required for embryonic development and viability, is downregulated in adult hearts, and is pathophysiologically upregulated in human end-stage heart failure. We applied quantitative immunoblotting and immunoprecipitation to native myocardial extracts, immunogold electron microscopy to cardiac tissue and membrane sections, electrophysiological recordings to whole hearts, and high-resolution tandem mass spectrometry to Cx45 fusion protein, and developed two new tools, anti-Cx45 antisera and Cre(+);Cx45 floxed mice, to facilitate characterization of Cx45 in adult mammalian hearts. We found that Cx45 represents 0.3% of total Cx protein (predominantly 200 fmol Cx43 protein/μg ventricular protein) and colocalizes with Cx43 in native ventricular gap junctions, particularly in the apex and septum. Cre(+);Cx45 floxed mice express 85% less Cx45, but do not exhibit overt electrophysiologic abnormalities. Although the basal phosphorylation status of native Cx45 remains unknown, CaMKII phosphorylates 8 Ser/Thr residues in Cx45 in vitro. Thus, although downregulation of Cx45 does not produce notable deficits in electrical conduction in adult, disease-free hearts, Cx45 is a target of the multifunctional kinase CaMKII, and the phosphorylation status of Cx45 and the role of Cx43/Cx45 heteromeric gap junction channels in both normal and diseased hearts merits further investigation.     

Mammoth interatrial septal aneurysm in the ICE age

Background

Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon.

Case Presentation

A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM) was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II), but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest); and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient), but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death.

Conclusion

Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM).