Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy.

AIMS: Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM. METHODS AND RESULTS: Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff-Parkinson-White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family. CONCLUSION: Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.

Advanced wound healing and NPWT: overcoming the challenges.

Nicholas Bunce, Editor of Nursing and Residential Care, discusses some highlights of the recent Hartmann LINK for Wound Healing Congress, which was organised in collaboration with the Journal of Wound Care.

Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI).

AIM: Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this double-blind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 µmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6-8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6-8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size -0.7% 95% CI: -2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6-8 days and at 6 months and final infarct size (FIS) measured at 6 months. CONCLUSIONS: Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size.

High levels of costimulatory receptors OX40 and 4-1BB characterize CD4+CD28null T cells in patients with acute coronary syndrome.

RATIONALE: Patients with acute coronary syndrome (ACS) predisposed to recurrent coronary events have an expansion of a distinctive T-cell subset, the CD4(+)CD28(null) T cells. These cells are highly inflammatory and cytotoxic in spite of lacking the costimulatory receptor CD28, which is crucial for optimal T cell function. The mechanisms that govern CD4(+)CD28(null) T cell function are unknown. OBJECTIVE: Our aim was to investigate the expression and role of alternative costimulatory receptors in CD4(+)CD28(null) T cells in ACS. METHODS AND RESULTS: Expression of alternative costimulatory receptors (inducible costimulator, OX40, 4-1BB, cytotoxic T lymphocyte associated antigen-4, programmed death-1) was quantified in CD4(+)CD28(null) T cells from circulation of ACS and stable angina patients. Strikingly, in ACS, levels of OX40 and 4-1BB were significantly higher in circulating CD4(+)CD28(null) T cells compared to classical CD4(+)CD28(+) T lymphocytes. This was not observed in stable angina patients. Furthermore, CD4(+)CD28(null) T cells constituted an important proportion of CD4(+) T lymphocytes in human atherosclerotic plaques and exhibited high levels of OX40 and 4-1BB. In addition, the ligands for OX40 and 4-1BB were present in plaques and also expressed on monocytes in circulation. Importantly, blockade of OX40 and 4-1BB reduced the ability of CD4(+)CD28(null) T cells to produce interferon-γ and tumor necrosis factor-α and release perforin. CONCLUSIONS: Costimulatory pathways are altered in CD4(+)CD28(null) T cells in ACS. We show that the inflammatory and cytotoxic function of CD4(+)CD28(null) T cells can be inhibited by blocking OX40 and 4-1BB costimulatory receptors. Modulation of costimulatory receptors may allow specific targeting of this cell subset and may improve the survival of ACS patients.

Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI).

BACKGROUND: Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial. METHODS AND OUTCOMES: The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6-8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6-8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6-8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6-8 days and six months. FUNDING, ETHICS AND REGULATORY APPROVALS: This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26). TRIAL REGISTRATION: ClinicalTrials.gov: NCT01388504 and Current Controlled Trials: ISRCTN57596739.

Arrhythmogenic cardiomyopathy and differential diagnosis with physiological right ventricular remodelling in athletes using cardiovascular magnetic resonance.

To describe the overlap between structural abnormalities typical of arrhythmogenic right ventricular cardiomyopathy (ARVC) and physiological right ventricular adaptation to exercise and differentiate between pathologic and physiologic findings using CMR. We compared CMR studies of 43 patients (mean age 49 ± 17 years, 49% males, 32 genotyped) with a definitive diagnosis of ARVC with 97 (mean age 45 ± 16 years, 61% males) healthy athletes. CMR was abnormal in 37 (86%) patients with ARVC, but only 23 (53%) fulfilled a major or minor CMR criterion according to the TFC. 7/20 patients who did not fulfil any CMR TFC showed pathological finding (RV RWMA and fibrosis in the LV or LV RWMA). RV was affected in isolation in 17 (39%) patients and 18 (42%) patients showed biventricular involvement. Common RV abnormalities included RWMA (n = 34; 79%), RV dilatation (n = 18; 42%), RV systolic dysfunction (≤ 45%) (n = 17; 40%) and RV LGE (n = 13; 30%). The predominant LV abnormality was LGE (n = 20; 47%). 22/32 (69%) patients exhibited a pathogenic variant: PKP2 (n = 17, 53%), DSP (n = 4, 13%) and DSC2 (n = 1, 3%). Sixteen (16%) athletes exceeded TFC cut-off values for RV volumes. None of the athletes exceeded a RV/LV end-diastolic volume ratio > 1.2, nor fulfilled TFC for impaired RV ejection fraction. The majority (86%) of ARVC patients demonstrate CMR abnormalities suggestive of cardiomyopathy but only 53% fulfil at least one of the CMR TFC. LV involvement is found in 50% cases. In athletes, an RV/LV end-diastolic volume ratio > 1.2 and impaired RV function (RVEF ≤ 45%) are strong predictors of pathology.

Cellulosimicrobium funkei: first report of infection in a nonimmunocompromised patient and useful phenotypic tests for differentiation from Cellulosimicrobium cellulans and Cellulosimicrobium terreum.

Cellulosimicrobium funkei is a rare, opportunistic pathogen. We describe a case of bacteremia and possibly prosthetic valve endocarditis by this organism in a nonimmunocompromised patient. Useful phenotypic tests for differentiating C. funkei from Cellulosimicrobium cellulans and Cellulosimicrobium terreum include motility, raffinose fermentation, glycogen, D-xylose, and methyl-α-D-glucopyranoside assimilation, and growth at 35°C.

Takotsubo cardiomyopathy associated with adrenal insufficiency in the context of long-term steroid use mimicking acute coronary syndrome.

Takotsubo cardiomyopathy (TCMP) is an important, though under-recognised, syndrome which mimics acute coronary syndrome (ACS) presenting with similar clinical, biochemical and ECG features. A 68-year-old man was referred as ACS for emergency coronary angiography; however, a history of lethargy, weight loss and electrolyte abnormalities prompted further investigations. Angiography was postponed, adrenal insufficiency confirmed and steroid replacement commenced. Echocardiography demonstrated reduced left ventricular (LV) function (45%) with regional wall motion abnormalities, although angiography confirmed unobstructed arteries. Steroid replacement induced a rapid improvement in symptoms and LV function. Few cases of TCMP associated with adrenal insufficiency have been reported. This appears to be the first case describing TCMP precipitated by new-onset secondary adrenal insufficiency following long-term steroid use in a male patient, and highlights the importance of considering TCMP in patients presenting with suspected ACS. Here, prompt recognition and treatment of a serious underlying disorder prevented a potentially life-threatening Addisonian crisis.

Impaired right ventricular systolic function demonstrated by reduced atrioventricular plane displacement in adults with Marfan syndrome.

AIMS: The right ventricle (RV) ejects the same volume of blood at the same rate as the left ventricle (LV). Mild LV dysfunction has been demonstrated in Marfan syndrome (MFS). However, little attention has been paid to the functioning of the RV. The aim of this study was to assess RV function in unoperated adult MFS patients. METHODS AND RESULTS: In 66 unoperated (15-58 years) MFS patients and 61 controls, rate of pressure rise (dp/dt) in RV, and tricuspid annular motion (TAM) were studied using conventional echocardiography and tissue Doppler imaging (TDI). When compared with controls, MFS patients showed impaired RV systolic function as expressed by a reduced dp/dt, TAM obtained by M-mode echocardiography, and peak TDI systolic velocities at the basal lateral wall (745.36+/-37.85 vs. 1103.30+/-27.30 mmHg, P<0.001; 2.2+/-0.05 vs. 2.5+/-0.05 cm, P<0.001; and 0.13+/-0.002 vs. 0.16+/-0.002 m/s, P<0.001, respectively). CONCLUSION: This study demonstrated a primary impairment of RV systolic function in MFS. This is the first study to report RV dysfunction in MFS. Such data could prove valuable during the peri-operative and long-term medical management of MFS patients.

Usefulness of changes in left ventricular wall thickness to predict full or partial pressure reperfusion in ST-elevation acute myocardial infarction.

Experimental studies have shown that if an acute transmural myocardial infarction is reperfused at full pressure there is an immediate and persisting increase in end-diastolic wall thickness (EDWT) due to massive intramural edema, with the amount of edema inversely related to the residual stenosis in the infarct-related artery. This study investigated if these findings are paralleled in the clinical setting and whether the resultant myocardial substrate differs after percutaneous coronary intervention (PCI) versus thrombolysis (the latter having a higher incidence of residual flow limiting stenosis in the culprit vessel). Eighty-eight consecutive patients with ST-elevation myocardial infarction were enrolled. Twenty-seven patients underwent primary PCI, 23 had rescue PCI, and 38 had thrombolysis. Standard M-mode and 2-dimensional echocardiographies were performed within 12 hours. Regional EDWT was measured in 904 infarct-related segments after the different reperfusion strategies and compared with 504 remote noninfarcted segments. EDWT of infarct-related segments after primary PCI was significantly increased compared with normal segments. At follow-up, after 6 months, EDWT of these segments was significantly decreased, indicating transmural infarction. EDWT of infarct-related segments after thrombolysis did not differ from that of normal segments. After rescue PCI, EDWT of infarct-related segments was significantly decreased compared with that of normal segments. In conclusion, full-pressure restoration of epicardial blood flow after transmural myocardial infarction causes an immediate increase in EDWT, easily detected by echocardiography. In contrast, pressure-limiting reperfusion (typical for thrombolysis) resultsin normal EDWT. This confirms experimental data that PCI and thrombolysis can differ in their resultant myocardial substrate.

Acute myocardial infarction complicating active ulcerative colitis: a case report.

Ulcerative colitis (UC) is a chronic inflammatory disease that predominantly affects the gastrointestinal (GI) tract but can involve extraintestinal organs including musculoskeletal system and skin. The most frequent cardiac manifestations of UC are pericarditis and myocarditis. Patients display an increased risk for venous thromboembolic complications and mesenteric ischemia, but the association with ischemic heart disease and myocardial infarction is uncertain. We present the case of a 27-year-old man with anti-PRIII ANCA-positive ulcerative colitis and increased factor VIII activity who presented with an acute myocardial infarction. We discuss possible causative links between these clinical entities and demonstrate the role of cardiac magnetic resonance (CMR) in patients with underlying inflammatory conditions who present with chest pain and evidence of myocardial damage.

The role of cardiovascular magnetic resonance in patients presenting with chest pain, raised troponin, and unobstructed coronary arteries.

AIMS: Troponin measurement is used in the assessment and risk stratification of patients presenting acutely with chest pain when the main cause of elevation is coronary artery disease. However, some patients have no coronary obstruction on angiography, leading to diagnostic uncertainty. We evaluated the incremental diagnostic value of cardiovascular magnetic resonance (CMR) in these patients. METHODS AND RESULTS: Sixty consecutive patients (mean age 44 years, 72% male) with a troponin-positive episode of chest pain and unobstructed coronary arteries were recruited within 3 months of initial presentation. All patients underwent CMR with cine imaging, T2-weighted imaging for detection of inflammation, and late gadolinium enhancement imaging for detection of infarction/fibrosis. An identifiable basis for troponin elevation was established in 65% of patients. The commonest underlying cause was myocarditis (50%), followed by myocardial infarction (11.6%) and cardiomyopathy (3.4%). In the 35% of patients where no clear diagnosis was identified by CMR, significant myocardial infarction/fibrosis was excluded. CONCLUSION: CMR is a valuable adjunct to conventional investigations in a diagnostically challenging and important group of patients with troponin-positive chest pain and unobstructed coronary arteries.

Combined coronary and perfusion cardiovascular magnetic resonance for the assessment of coronary artery stenosis.

The purpose of this study was to evaluate the feasibility and accuracy of combined coronary and perfusion cardiovascular magnetic resonance (CMR) in the assessment of coronary artery stenosis. Thirty-five consecutive patients (27 men, eight women, age range 34-81 years), undergoing cardiac catheterization, were assessed with 3D coronary CMR and rest-stress perfusion CMR. Significant coronary stenosis was determined by vessel narrowing or signal loss with coronary CMR, and by abnormal contrast enhancement with perfusion CMR. Coronary artery diameter stenosis greater than 50% was considered significant with conventional cardiac catheterization. Seventeen patients had significant coronary artery disease, and in these there were 35 significant stenoses on cardiac catheterization. All left main stem arteries were normal on both cardiac catheterization and coronary CMR. For the diagnosis of coronary artery stenosis, coronary CMR had a sensitivity of 92% for the left anterior descending artery (LAD), 79% for the right coronary artery (RCA), but only 13% for the circumflex coronary artery (LCX). Perfusion CMR had corresponding sensitivities of 69%, 86%, and 63%, respectively. For all arteries the accuracies for coronary and perfusion CMR were 67% and 72%, respectively. Combining coronary and perfusion CMR improved the accuracy to 77%. These data demonstrate that in patients with suspected coronary artery disease, combined coronary and perfusion CMR is feasible, increases the accuracy of detection of significant coronary stenosis, and offers the possibility of combined anatomical and hemodynamic assessment of coronary artery stenosis.

Coronary artery bypass graft patency: assessment with true ast imaging with steady-state precession versus gadolinium-enhanced MR angiography.

PURPOSE: To compare the accuracy of multisection true fast imaging with steady-state precession (FISP) with gadolinium-enhanced magnetic resonance (MR) angiography for the detection of coronary artery bypass graft patency. MATERIALS AND METHODS: Twenty-five patients with coronary artery bypass grafts who had recently undergone conventional coronary angiography underwent MR angiography with a 1.5-T system. True FISP angiographic images were acquired in transverse and coronal planes. Coronal cardiac-gated MR angiography was performed with 0.2 mL per kilogram of body weight of gadopentetate dimeglumine injected at a rate of 2 mL/sec. With conventional angiography as the reference standard, the sensitivity, specificity, and accuracy of each technique for the detection of graft patency were determined. Image quality and duration of analysis were determined by two experienced radiologists. RESULTS: In 25 patients, 46 of 56 venous grafts were patent and 22 of 23 arterial grafts were patent. In all grafts at true FISP angiography, sensitivity for patency was 84% (57 of 68 grafts), specificity was 45% (five of 11 grafts), and accuracy was 78% (62 of 79 grafts). At MR angiography, sensitivity was 85% (58 of 68 grafts), specificity was 73% (eight of 11 grafts), and accuracy was 84% (66 of 79 grafts) (difference not significant). Image quality scores were similar with both techniques, but duration of analysis was significantly longer with MR angiography than with true FISP angiography (29 minutes 24 seconds vs 14 minutes 6 seconds, P <.001). CONCLUSION: Accuracy for detection of coronary artery bypass graft patency was similar with gadolinium-enhanced MR angiography and true FISP angiography, with a trend toward more false-positive findings for occlusion and reduced visualization of arterial grafts with true FISP angiography.

Coronary artery anomalies: assessment with free-breathing three-dimensional coronary MR angiography.

PURPOSE: To evaluate a simplified protocol by using free-breathing three-dimensional (3D) coronary magnetic resonance (MR) angiography to determine the anatomy of anomalous coronary arteries, in particular the relationship of the vessels to the aortic root. MATERIALS AND METHODS: Twenty-six patients (18 men, eight women; mean age, 50 years; age range, 18-77 years) who had a history of chest pain, palpitations, or syncope and who were suspected of having coronary artery anomalies were examined with free-breathing MR angiography. Multiple 3D volume slabs were acquired at the level of the sinuses of Valsalva by using diaphragmatic navigators for respiratory artifact suppression. The proximal anatomy of the coronary arteries was determined. RESULTS: Six anomalous circumflex arteries originated from the right sinus of Valsalva and passed behind the aortic root. Six right coronary arteries arose from the left sinus of Valsalva and coursed between the aortic root and the right ventricular outflow tract (RVOT). Nine left coronary arteries arose from the right sinus of Valsalva; seven of nine coursed between the aortic root and the RVOT. Five patients had minor anomalies. Overall, in eight patients with anomalous arteries that coursed between the aortic root and the RVOT, conventional coronary angiography could not be used confidently to identify the proximal course. CONCLUSION: Free-breathing 3D coronary MR angiography can be used to identify the proximal anatomy of anomalous coronary arteries.

Initial experience with the intravascular contrast agent NC100150-injection (Clariscan) for breath-hold and navigator-gated magnetic resonance coronary artery imaging.

PURPOSE: To examine magnetic resonance coronary artery imaging after NC100150-Injection. MATERIALS AND METHODS: Breath-hold and navigator-gated images were acquired in five patients. RESULTS: Breath-hold image quality, coronary artery-fat SDNR, and coronary artery SNR improved. Respiratory artifacts due to reduced liver signal intensity degraded navigator-gated image quality. CONCLUSION: NC100150-Injection improves breath-hold coronary artery imaging. Navigator-gated acquisitions should use techniques that are insensitive to T2* effects.