SHROOM3 is downstream of the planar cell polarity pathway and loss-of-function results in congenital heart defects.

Congenital heart disease (CHD) is the most common birth defect, and the leading cause of death due to birth defects, yet causative molecular mechanisms remain mostly unknown. We previously implicated a novel CHD candidate gene, SHROOM3, in a patient with CHD. Using a Shroom3 gene trap knockout mouse (Shroom3gt/gt) we demonstrate that SHROOM3 is downstream of the noncanonical Wnt planar cell polarity signaling pathway (PCP) and loss-of-function causes cardiac defects. We demonstrate Shroom3 expression within cardiomyocytes of the ventricles and interventricular septum from E10.5 onward, as well as within cardiac neural crest cells and second heart field cells that populate the cardiac outflow tract. We demonstrate that Shroom3gt/gt mice exhibit variable penetrance of a spectrum of CHDs that include ventricular septal defects, double outlet right ventricle, and thin left ventricular myocardium. This CHD spectrum phenocopies what is observed with disrupted PCP. We show that during cardiac development SHROOM3 interacts physically and genetically with, and is downstream of, key PCP signaling component Dishevelled 2. Within Shroom3gt/gt hearts we demonstrate disrupted terminal PCP components, actomyosin cytoskeleton, cardiomyocyte polarity, organization, proliferation and morphology. Together, these data demonstrate SHROOM3 functions during cardiac development as an actomyosin cytoskeleton effector downstream of PCP signaling, revealing SHROOM3's novel role in cardiac development and CHD.

Effects of Septal Reduction Therapy on Acute Cardiovascular Events and All-Cause Mortality in Patients with Hypertrophic Cardiomyopathy.

Septal reduction therapy (SRT) -i.e. septal myectomy and alcohol septal ablation-has been performed to treat medically refractory hypertrophic cardiomyopathy (HCM) for decades. However, it is largely unknown whether SRT prevents HCM-related cardiovascular events or death. The objective was to examine the effects of SRT on acute cardiovascular events and all-cause mortality in HCM. We performed a propensity score (PS) -matched study using databases that capture all hospitalizations and outpatient visits in New York state. We identified patients with HCM who underwent SRT between 2007 and 2014 (i.e. the SRT group) and those who had never had SRT but had at least one hospitalization for HCM during the same period (i.e. the control group). We performed PS matching at a 1:1 ratio. The primary outcome was a composite of acute cardiovascular events and all-cause mortality during 0-180 days and 181-360 days. The secondary outcome was 180- and 360-day all-cause mortality. We included 846 patients with HCM (423 PS-matched pairs). Patients who underwent SRT had a lower risk of the primary outcome event (0-180 days: odds ratio [OR], 0.54; 95% confidence intervals (CI), 0.37-0.80; P = 0.002 and 181-360 days: OR, 0.33; 95% CI, 0.22-0.51; P < 0.0001). Furthermore, the risk of all-cause mortality was lower at 180 days (OR, 0.37; 95% CI, 0.22-0.63; P = 0.0003) and 360 days post-SRT (OR, 0.32; 95% CI, 0.20-0.51; P < 0.0001). In conclusion, our PS-matched study using population-based datasets demonstrated that SRT was associated with a reduced risk of a composite of acute cardiovascular events and all-cause mortality in HCM during the first post-SRT year.

Intracardiac Delineation of Septal Conduction in Left Bundle-Branch Block Patterns.

BACKGROUND: Septal activation in patients with left bundle-branch block (LBBB) patterns has not been described previously. We performed detailed intracardiac mapping of left septal conduction to assess for the presence and level of complete conduction block (CCB) in the His-Purkinje system. Response to His bundle pacing was assessed in patients with and without CCB in the left bundle. METHODS: Left septal mapping was performed with a linear multielectrode catheter in consecutive patients with LBBB pattern referred for device implantation (n=38) or substrate mapping (n=47). QRS width, His duration, His-ventricular (HV) intervals, and septal conduction patterns were analyzed. The site of CCB was localized to the level of the left-sided His fibers (left intrahisian) or left bundle branch. Patients with ventricular activation preceded by Purkinje potentials were categorized as having intact Purkinje activation. RESULTS: A total of 88 left septal conduction recordings were analyzed in 85 patients: 72 LBBB block pattern and 16 controls (narrow QRS, n=11; right bundle-branch block, n=5). Among patients with LBB block pattern, CCB within the proximal left conduction system was observed in 64% (n=46) and intact Purkinje activation in the remaining 36% (n=26). Intact Purkinje activation was observed in all controls. The site of block in patients with CCB was at the level of the left His bundle in 72% and in the proximal left bundle branch in 28%. His bundle pacing corrected wide QRS in 54% of all patients with LBBB pattern and 85% of those with CCB (94% left intrahisian, 62% proximal left bundle-branch). No patients with intact Purkinje activation demonstrated correction of QRS with His bundle pacing. CCB showed better predictive value (positive predictive value 85%, negative predictive value 100%, sensitivity 100%) than surface ECG criteria for correction with His bundle pacing. CONCLUSIONS: Heterogeneous septal conduction was observed in patients with surface LBBB pattern, ranging from no discrete block to CCB. When block was present, we observed pathology localized within the left-sided His fibers (left intrahisian block), which was most amenable to corrective His bundle pacing by recruitment of latent Purkinje fibers. ECG criteria for LBBB incompletely predicted CCB, and intracardiac data might be useful in refining patient selection for resynchronization therapy.

Congenitally corrected transposition of the great arteries: is it really a transposition? An anatomical study of the right ventricular septal surface.

Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital malformation which associates discordant atrioventricular and ventriculo-arterial connections. Although frequently associated with a ventricular septal defect (VSD), its anatomy remains controversial. This could be due in hearts with usual atrial arrangement to the apparently different anatomy of the left-sided right ventricle compared with a right-sided right ventricle. We wanted to compare the RV septal anatomy between ccTGA, transposition of the great arteries and normal heart and to determine the anatomy of the VSD in ccTGA. We analysed 102 human heart specimens: 31 ccTGA, 36 transpositions of the great arteries, 35 normal hearts. According to the last classification of VSD (ICD-11), VSD were classified as outlet if located above the superoseptal commissure of the tricuspid valve and inlet if underneath. We measured the lengths of the superior and inferior limbs of the septal band and the angle between the two limbs. To assess the orientation of the septal band, we also measured the angle between superior limb and the arterial valve above. A VSD was present in 26 ccTGA (84%) and was an outlet VSD in 16 cases (61%). The mean angle between the two limbs of the septal band was 76.4° for ccTGA compared with 90.6° for transposition of the great arteries (P = 0.011) and 76.1° for normal hearts (P= NS). The mean angle between the superior limb of the septal band and the arterial valve above was 70.6° for ccTGA compared with 90.6° for transposition of the great arteries (P = 0.0004) and 69.1° for normal hearts (P= NS). The inferior limb of the septal band was significantly shorter in ccTGA (P < 0.0003): SL/IL length ratio was 21.4 for ccTGA, 2.2 for transposition of the great arteries and 1.5 for normal hearts. The typical VSD in ccTGA is an outlet VSD. Its frequent misdiagnosis as an inlet VSD might be explained by the shortness of the inferior limb, which creates the illusion of a posterior VSD, and by the fact that the VSD is usually assessed from the left ventricular aspect. Surprisingly, the orientation of the septal band is similar in ccTGA and normal heart, despite the discordant atrioventricular connections, and different in ccTGA and transposition of the great arteries, despite the discordant ventriculo-arterial connections. These findings suggest that the mechanism leading to transposition in ccTGA and in TGA probably is different. The term 'double discordance' might therefore be more appropriate as a description of this complex anomaly.

Stereotactic body radiotherapy for ventricular tachycardia (cardiac radiosurgery) : First-in-patient treatment in Germany.

PURPOSE: Single-session cardiac stereotactic body radiotherapy, called cardiac radiosurgery (CRS) or radioablation (RA), may offer a potential treatment option for patients with refractory ventricular tachycardia (VT) and electrical storm who are otherwise ineligible for catheter ablation. However, there is only limited clinical experience. We now present the first-in-patient treatment using (CRS/RA) for VT in Germany. METHODS: A 78-year-old male patient with dilated cardiomyopathy and significantly reduced ejection fraction (15%) presented with monomorphic VT refractory to poly-anti-arrhythmic medication and causing multiple implantable cardioverter-defibrillator (ICD) interventions over the course of several weeks, necessitating prolonged treatment on an intensive care unit. Ultra-high-resolution electroanatomical voltage mapping (EVM) revealed a re-entry circuit in the cardiac septum inaccessible for catheter ablation. Based on the EVM, CRS/RA with a single session dose of 25 Gy (83% isodose) was delivered to the VT substrate (8.1 cc) using a c-arm-based high-precision linear accelerator on November 30, 2018. RESULTS: CRS/RA was performed without incident and dysfunction of the ICD was not observed. Following the procedure, a significant reduction in monomorphic VT from 5.0 to 1.6 episodes per week and of ICD shock interventions by 81.2% was observed. Besides periprocedural nausea with a single episode of vomiting, no treatment-associated side effects were noted. Unfortunately, the patient died 57 days after CRS/RA due to sepsis-associated cardiac circulatory failure after Clostridium difficile-associated colitis developed during rehabilitation. Histopathologic examination of the heart as part of a clinical autopsy revealed diffuse fibrosis on most sections of the heart without apparent differences between the target area and the posterior cardiac wall serving as a control. CONCLUSION: CRS/RA appears to be a possible treatment option for otherwise untreatable patients suffering from refractory VT and electrical storm. A relevant reduction in VT incidence and ICD interventions was observed, although long-term outcome and consequences of CRS/RA remain unclear. Clinical trials are strongly warranted and have been initiated.

Effect of cardiac resynchronization therapy on septal perfusion and septal thickening: Association with left ventricular function, reverse remodelling and dyssynchrony.

BACKGROUND: We evaluated the effect of cardiac resynchronization therapy (CRT) on septal perfusion and thickening at 6 months post implantation assessed on Tc99m-MIBI Gated myocardial perfusion SPECT (GMPS).We also studied the association of change in septal perfusion and thickening with primary outcome defined as at least one [improvement in ≥1NYHA class, left ventricular ejection fraction (LVEF) by ≥ 5%, reduction of end-systolic volume (ESV) by ≥ 15%, and improvement ≥ 5 points in Minnesota living with heart failure questionnaire (MLHFQ)]. METHOD: One hundred and five patients underwent clinical and GMPS evaluation before and at 6 months post CRT. RESULT: Post CRT there was significant improvement in mean normalized septal perfusion uptake and in septal thickening (P value = 0.001, both). There was no significant relation between improvement in septal perfusion and primary outcome. However, improvement in septal thickening was statistically significant with favorable primary outcome (P = 0.001).There was no significant correlation between improvement of septal perfusion and improvement in LVEF, reduction in End diastolic volume (EDV), ESV, and Left ventricular Dyssynchrony (LVD). But, there was significant correlation between improvement of septal thickening and these parameters. CONCLUSION: Improvement in septal thickening was associated with reverse remodeling, improvement in LVEF, and reduction of LVD.

Lipomatous hypertrophy of the interatrial septum is a pathologic, not an anatomic diagnosis.

BACKGROUND AND AIM: Lipomatous hypertrophy of the interatrial septum (LHIS), a fatty tumor, is usually diagnosed on both echo and CT/MRI imaging. Cases of LHIS located outside of the interatrial septum are extremely rare and rarer still are these cases large enough to cause symptoms. The clinical literature demonstrates a misunderstanding that fatty tumors outside the intra-atrial area represent lipomas. However, pathologic understanding of these fatty tumors is clear and is based on microscopic findings. METHODS: The tumor was removed by diving the base of attachment at the left ventricular apex via a median sternotomy on cardiopulmonary bypass. RESULTS: The patient made an uneventful recovery and remains well at 6 months postoperatively. CONCLUSIONS: On rare occasions, LHIS can arise from outside the interatrial septum. An LHIS can be differentiated from a lipoma by the presence of entrapped cardiac myocytes in LHIS, making it a pathological, rather than an anatomic, diagnosis.

Short- and long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy in patients with mild left ventricular hypertrophy: a propensity score matching analysis.

AIMS: Based on European guidelines, alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) is indicated only in patients with interventricular septum (IVS) thickness >16 mm. The aim of this study was to evaluate the short- and long-term outcomes in ASA patients with mild hypertrophy (IVS ≤ 16 mm). METHODS AND RESULTS: We retrospectively evaluated 1505 consecutive ASA patients and used propensity score to match 172 pairs (344 patients) in groups IVS ≤ 16 mm or IVS > 16 mm. There was no occurrence of post-ASA ventriculoseptal defect in the whole cohort (n = 1505). Matched patients had 30-day mortality rate 0% in IVS ≤ 16 mm group and 0.6% in IVS > 16 mm group (P = 1). Patients in IVS ≤ 16 mm group had more ASA-attributable early complications (16% vs. 9%; P = 0.049), which was driven by higher need for pacemaker implantation (13% vs. 8%; P = 0.22). The mean follow-up was 5.4 ± 4.3 years and the annual all-cause mortality rate was 1.8 and 3.2 deaths per 100-patient-years in IVS ≤ 16 group and IVS > 16 group, respectively (log-rank test P = 0.04). There were no differences in symptom relief and left ventricular (LV) gradient reduction. Patients with IVS ≤ 16 mm had less repeated septal reduction procedures (log-rank test P = 0.03). CONCLUSION: Selected patients with HOCM and mild hypertrophy (IVS ≤ 16 mm) had more early post-ASA complications driven by need for pacemaker implantation, but their long-term survival is better than in patients with IVS >16 mm. While relief of symptoms and LV obstruction reduction is similar in both groups, a need for repeat septal reduction is higher in patients with IVS > 16 mm.

Cardiac magnetic resonance in hypertrophic and dilated cardiomyopathies.

Cardiomyopathies are a heterogeneous entity. The progress in the field of genetics has allowed over the years to determine its origin more and more often. The classification of these pathologies has changed over the years; it has been updated with new knowledge. Imaging allows to define the phenotypic characteristics of the different forms of cardiomyopathy. Cardiac magnetic resonance (CMR) allows a morphological evaluation of the associated (and sometimes pathognomonic) cardiac findings of any form of cardiomyopathy. The tissue characterization sequences also make magnetic resonance imaging unique in its ability to detect changes in myocardial tissue. This review aims to define the features that can be highlighted by CMR in hypertrophic and dilated forms and the possible differential diagnoses. In hypertrophic forms, CMR provides: precise evaluation of wall thickness in all segments, ventricular function and size and evaluation of possible presence of areas of fibrosis as well as changes in myocardial tissue (measurement of T1 mapping and extracellular volume values). In dilated forms, cardiac resonance is the gold standard in the assessment of ventricular volumes. CMR highlights also the potential alterations of the myocardial tissue.

Hypertrophic Obstructive Cardiomyopathy: Surgical Myectomy and Septal Ablation.

Hypertrophic cardiomyopathy is a genetic disorder characterized by marked hypertrophy of the myocardium. It is frequently accompanied by dynamic left ventricular outflow tract obstruction and symptoms of dyspnea, angina, and syncope. The initial therapy for symptomatic patients with obstruction is medical therapy with ß-blockers and calcium antagonists. However, there remain a subset of patients who have continued severe symptoms, which are unresponsive to medical therapy. These patients can be treated with septal reduction therapy, either surgical septal myectomy or alcohol septal ablation. When performed by experienced operators working in high-volume centers, septal myectomy is highly effective with a >90% relief of obstruction and improvement in symptoms. The perioperative mortality rate for isolated septal myectomy in most centers is <1%. Alcohol septal ablation is a less invasive treatment. In many patients, the hemodynamic and clinical results are comparable to that of septal myectomy. However, the results of alcohol septal ablation are dependent on the septal perforator artery supplying the area of the contact between the hypertrophied septum and the anterior leaflet of the mitral valve. There are some patients, particularly younger patients with severe hypertrophy, who do not uniformly experience complete relief of obstruction and symptoms. Both techniques of septal reduction therapy are highly operator dependent. The final decision as to which approach should be selected in any given patient is dependent up patient preference and the availability and experience of the operator and institution at which the patient is being treated.

Intra-procedural evaluation of the cavo-tricuspid isthmus anatomy with different techniques: comparison of angiography and intracardiac echocardiography.

Cavo-tricuspid isthmus (CTI) anatomies are highly variable, and specific anatomies lead to a difficult CTI ablation. This study aimed to compare the clinical utility of angiography and intracardiac echocardiography (ICE) in evaluating CTI anatomies, and to investigate the impact of the CTI anatomy on the procedure when the ablation tactic was adjusted to the anatomy. This study included 92 consecutive patients who underwent a CTI ablation. The CTI morphology was assessed with both right atrial angiography and ICE before the ablation, and the ablation tactic was adjusted to the anatomy. The mean CTI length was 34 ± 9 mm. On ICE imaging, 21 (23%) patients had a flat CTI, while 41 (45%) had a concave CTI with a mean depth of 5.6 ± 2.7 mm. The remaining 30 (32%) had a distinct pouch with a mean depth of 6.4 ± 2.3 mm, located at the posterior, middle, and anterior isthmus in 15, 14, and 1 patients, respectively. The Eustachian ridge (ER) was visualized in 46 (50%) patients. On angiography, a pouch and ER were detected in 22 and 15 patients, but not in the remaining 8 and 31, respectively. A complete CTI block line was created in all patients without any complications. The CTI anatomy did not significantly impact any procedural parameters. ICE was superior to angiography in evaluating the detailed CTI anatomy, especially pouches and the ER. An adjustment of the ablation tactic to the anatomy could overcome the procedural difficulties of the CTI ablation in cases with specific anatomies.

Contemporary Septal Reduction Therapy in Drug-Refractory Hypertrophic Obstructive Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a complex and relatively common genetic cardiac disease that has been the subject of intense investigation for over 50 years. Most patients with HCM are asymptomatic, but some develop symptoms, often many years after the appearance of electrocardiographic or echocardiographic evidence of left ventricular hypertrophy. Symptoms due to the left ventricular outflow tract obstruction frequently worsen over time, requiring septal reduction therapy (SRT) despite optimal medical therapy. Percutaneous transluminal septal myocardial ablation (PTSMA) and surgical myectomy are collectively known as SRT. In this review, we will focus on the emerging concept and practical implication of SRT and the available evidence on either PTSMA or surgical myectomy in the literature.

Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is a myocardial disease characterized by fibrosis and microvascular ischemia. Microvessels play a critical role in myocardial fibrosis in HOCM. However, it remains unclear whether or not myocardial fibrosis is associated with microvascular density (MVD) changes. OBJECTIVE: The aim of the present study was to investigate whether a reduction in MVD is related to myocardial fibrosis in HOCM cardiac samples. METHODS: We analyzed MVD and fibrosis in myectomy left ventricular (LV) septal wall specimens from 53 HOCM patients. Control myocardium from the LV septal wall was collected at autopsy of 9 individuals who died of noncardiac causes. RESULTS: The fibrosis ratio (% area) in HOCM was higher and the MVD was lower than that in control subjects (i.e., 12.7 ± 10.0 vs. 4.0 ± 1.4%, p = 0.012, and 480.9 ± 206.7 vs. 1,425 ± 221/mm2, p < 0.001). Patients with mild fibrosis had a higher MVD than patients with moderate fibrosis (i.e., 568.2 ± 214.8 vs. 403.2 ± 167.8/mm2, p = 0.006) and patients with severe fibrosis (i.e., 568.2 ± 214.8 vs. 378.6 ± 154.0/mm2, p = 0.024). Furthermore, a significant negative correlation was found between myocardial fibrosis and MVD in HOCM patients (r = -0.40, p = 0.003), which was also found in mild fibrosis (r = -0.40, p = 0.043), moderate fibrosis (r = -0.50, p = 0.024), and severe fibrosis (r = -0.24, p = 0.61), although no significant differences were observed in severe fibrosis. Additionally, we demonstrated that late gadolinium enhancement was negatively correlated with MVD (r = -0.37, p = 0.03) and positively correlated with fibrosis (r = 0.44, p = 0.01). CONCLUSION: HOCM patients had a higher myocardial fibrosis ratio and a lower MVD. The severity of myocardial fibrosis was negatively correlated with MVD in HOCM. These findings showed that a reduced MVD may contribute to myocardial fibrosis in HOCM.

Cystamine slows but not inverses the progression of monocrotaline-induced pulmonary arterial hypertension in rats.

Tissue transglutaminase (TG2) plays an important role in pulmonary arterial hypertension (PAH). Previous research indicate that TG2 and protein serotonylation catalyzed by TG2 are upregulated in PAH. Serotonin transporter inhibitor fluoxetine ameliorates PAH via inhibition of protein serotonylation. It is still unknown whether PAH is inhibited through direct inhibition of TG2. Therefore, the present study aimed to investigate the effects of TG2 inhibitor cystamine on monocrotaline-induced PAH in rats. Rats were treated with monocrotaline (60 mg·kg-1, i.p.) in combination with or without cystamine (20, 40 mg·kg-1·day-1, p.o.). The results showed that compared with monocrotaline alone, combination of monocrotaline with cystamine (40 mg·kg-1·day-1, p.o.) relieved right ventricle hypertrophy, inhibited pulmonary arteriolar remodeling, and downregulated protein expression of TG2, phosphorylated protein kinase B (Akt), and extracellular regulated protein kinase (ERK) at day 21. However, except for TG2 expression, these changes were not significantly inhibited by cystamine at day 35. In addition, cystamine dose-dependently enhanced the survival rate of rats injected with monocrotaline at day 35. The findings suggest that cystamine slows but not reverses monocrotaline-induced PAH in rats, which was largely associated with the inhibition of TG2 protein expression and Akt and ERK activation.

A QS pattern in leads V1 and V2 is associated with septal scarring independent of scar etiology - A cardiac magnetic resonance imaging study.

BACKGROUND: Isolated septal myocardial infarction (MI) is traditionally characterized by the presence of pathological Q waves in leads V1 and V2 on the surface electrocardiogram (ECG). The purpose of this study was to determine the relation between this ECG pattern and septal scar on cardiac magnetic resonance (CMR) imaging. METHODS: We retrospectively reviewed the medical records of 996 consecutive patients who received both ECG and CMR. RESULTS: Nineteen patients had a Q wave in leads V1 and V2. Septal scar was present in all 19 patients. Based on CMR imaging criteria, septal scars were ischemic in 8 patients (42%) and non-ischemic in 11 patients (58%). CONCLUSION: The results suggest that the presence of a QS pattern in leads V1 and V2 on the surface ECG is highly predictive of the presence of a septal myocardial scar, but is not diagnostic for septal MI, even after excluding comorbidities known to produce a pseudo-septal MI pattern.

Release kinetics of inflammatory biomarkers in a clinical model of acute myocardial infarction.

RATIONALE: Inflammation in the setting of acute myocardial infarction (MI) has been linked to risk stratification; however, the release kinetics of inflammatory biomarkers in patients with acute MI has been difficult to establish. OBJECTIVE: The aim of this study was to determine the kinetics of changes in the levels of several biomarkers specifically linked to inflammation after transcoronary ablation of septal hypertrophy, a procedure that mimics acute MI. METHODS AND RESULTS: We analyzed release kinetics of C-reactive protein, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and peripheral blood leukocyte subsets in patients (n=21) undergoing transcoronary ablation of septal hypertrophy. Blood samples were collected before transcoronary ablation of septal hypertrophy and at various times after transcoronary ablation of septal hypertrophy. Serum levels of C-reactive protein were increased at 24 hours (1.0 mg/dL [interquartile range [IQR], 0.7-1.75] versus 0.2 mg/dL [IQR, 0.1-1.05] at baseline [BL]; P<0.001), whereas high-sensitivity C-reactive protein increased as early as 8 hours (2.68 mg/L [IQR, 1.23-11.80] versus 2.17 mg/L [IQR, 1.15-5.06] at BL; P=0.002). Interleukin-6 was significantly increased at 45 minutes (2.59 pg/mL [IQR, 1.69-5.0] versus 1.5 pg/mL [IQR, 1.5-2.21] at BL; P=0.002), and soluble CD40 ligand was significantly decreased at 60 minutes (801.6 pg/mL [IQR, 675.0-1653.5] versus 1750.0 pg/mL [IQR, 1151.0-2783.0] at BL; P=0.016). Elevated counts of polymorphonuclear neutrophils were detectable at 15 minutes, with a significant increase at 2 hours (6415 cells/µL [IQR, 5288-7827] versus 4697 cells/µL [IQR, 2892-5620] at BL; P=0.004). Significant monocytosis was observed at 24 hours (729 cells/µL [IQR, 584-1344] versus 523 cells/µL [IQR, 369-701] at BL; P=0.015). CONCLUSIONS: Interleukin-6 and neutrophil granulocytes showed a continuous rise at all prespecified time points after induction of MI. Our results provide valuable additional evidence of the diagnostic value of inflammatory biomarkers in the setting of early acute MI.

Release kinetics of high-sensitivity cardiac troponins I and T and troponin T upstream open reading frame peptide (TnTuORF) in clinically induced acute myocardial infarction.

CONTEXT: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes. OBJECTIVE: The study examined the early release kinetics of TnTuORF. MATERIALS AND METHODS: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n = 31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH). RESULTS: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18 ng/L versus 27 ng/L; cTnI median: 15 ng/L versus 25 ng/L). TnTuORF showed no variation. DISCUSSION: We observed a significantly greater increase in cTnI compared with cTnT. CONCLUSION: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting.

Global Longitudinal Strain in master athletes and in hypertensive patients with the same degree of septal thickness.

Athletes may have electrocardiogram (ECG) repolarization abnormalities during stress test suggestive for ischemia in the absence of ischemic coronary artery disease, often in a setting of myocardial septum hypertrophy. Global longitudinal strain (GLS) might be altered in these athletes compared to hypertensive patients with the same degree of septal thickness. About 735 consecutive athletes were screened for mandatory assessment of fitness to participate in competitive sports. At the stress test, 23 (19 M, 4 F) were found to have ECG repolarization abnormalities suggestive for ischemia in the presence of normal coronary vessels. They were matched to a control group of 23 hypertensive patients with no ECG abnormalities during stress test and the same degree of septal thickness. A transthoracic echocardiography for evaluation of global longitudinal strain (GLS) was performed. Interventricular septum thickness (IST) and relative wall thickness (RWT) were also calculated. A preserved ventricular function was seen in both groups (64 ± 8% in cases vs 60 ± 6% in controls, P = 0.42). IST and RWT were not significantly different. GLS was significantly lower in athletes vs hypertensive patients (-18.7 ± 2.5 vs -21.67 ± 0.27, P = 0.001). In athletes with septal hypertrophy and a positive stress test not associated to coronary disease, GLS is lower with respect to a population of hypertensive patient with the same degree of septal hypertrophy. Further investigations in a larger population are required to better define the potentiality of GLS in differentiating pathological vs physiological septum hypertrophy.

The evolution of basal septal hypertrophy: From benign and age-related normal variant to potentially obstructive and symptomatic cardiomyopathy.

Localized thickening of the basal portion of the ventricular septum or basal septal hypertrophy (BSH) has been identified both at autopsy and by imaging studies for decades; despite numerous investigations, there is no consensus on the significance of this finding and a remarkable lack of consistency in terminology. This paper summarizes the scientific literature on the topic, focusing on recent echocardiographic findings. A case description illustrating some of the complex issues involved in measurement and diagnosis and differentiation from sigmoidal hypertrophic cardiomyopathy (HCM) is presented. Criteria are proposed for diagnosing pathologic BSH which include the following: (1) Exertional symptoms compatible with left ventricular outflow tract obstruction (LVOTO) such as dyspnea, near-syncope, and chest discomfort; (2) Documented LVOTO gradient demonstrated at peak bicycle or post-treadmill exercise >30 mm Hg; and (3) Symptomatic improvement with ß-blocker (or other negative inotropic) therapy (preferably accompanied by documentation of reduction of exercise-induced LVOT).

Decreased left atrial myocardial strain in patients with suboptimal blood pressure control.

BACKGROUND: Suboptimal blood pressure (BP) control is commonly observed in patients receiving antihypertensive agents, but the relationship between uncontrolled BP and left atrial (LA) impairment remains unknown. METHODS: This study enrolled 279 hypertensive patients who had been medicated, as well as 85 matched normal controls. The BP of systolic <140 mmHg and diastolic<90 mmHg was defined as optimal (HT1 group, n=146), otherwise as suboptimal BP control (HT2 group, n = 133). LA myocardial function was assessed by the systolic (SSa), early diastolic (SEa), and late diastolic (SAa) LA strains. RESULTS: Both the HT1 group and HT2 group had higher BP reading, thicker interventricular septum, larger LA volume index, and enhanced active atrial emptying fraction than the control group (all <0.05). When compared with normal subjects, hypertensive patients displayed obvious reduction in the SSa (50.0 ± 10.9 vs. 35.9 ± 8.0%), SEa (30.1 ± 7.7 vs. 18.5 ± 7.1%) and SAa (19.9 ± 6.4 vs. 17.8 ± 4.2%) (all p < 0.001). In addition to a further impaired SEa found in the HT2 group than in the HT1 group (17.2 ± 5.3 vs. 19.8 ± 8.3%, p = 0.002), the treated BP of >140/90 mmHg appeared an independent risk factor associated with the abnormal SEa (odds ratio, 2.957; interval of confidence, 1.614-5.415; p = 0.001). CONCLUSIONS: Suboptimal BP control status in hypertensive patients is related to a further reduction of LA myocardial function assessed by the novel 2DSTI free strain, and suboptimal BP might be regarded as a composite risk factor and therefore a simplified treatment target. However, the prognostic value of LA free strain in patients with inability to achieve the BP target needs to be evaluated in future prospective studies.