The Prevalence and Characteristics of Arrhythmic Mitral Valve Prolapse in Patients With Unexplained Cardiac Arrest.

BACKGROUND: There is growing evidence that mitral valve prolapse (MVP) is associated with otherwise unexplained cardiac arrest (UCA). However, reports are hindered by the absence of a systematic ascertainment of alternative diagnoses. OBJECTIVES: This study reports the prevalence and characteristics of MVP in a large cohort of patients with UCA. METHODS: Patients were enrolled following an UCA, defined as cardiac arrest with no coronary artery disease, preserved left ventricular ejection fraction, and no apparent explanation on electrocardiogram. A comprehensive evaluation was performed, and patients were diagnosed with idiopathic ventricular fibrillation (IVF) if no cause was found. Echocardiography reports were reviewed for MVP. Patients with MVP were divided into 2 groups: those with IVF (AMVP) and those with an alternative diagnosis (nonarrhythmic MVP). Patient characteristics were then compared. The long-term outcomes of AMVP were reported. RESULTS: Among 571 with an initially UCA, 34 patients had MVP (6%). The prevalence of definite MVP was significantly higher in patients with IVF than those with an alternative diagnosis (24 of 366 [6.6%] vs 5 of 205 [2.4%]; P = 0.03). Bileaflet prolapse was significantly associated with AMVP (18 of 23 [78%] vs 1 of 8 [12.5%]; P = 0.001; OR: 25.2). The proportion of patients with AMVP who received appropriate implantable cardioverter-defibrillator therapies over a median follow-up of 42 months was 21.1% (4 of 19). CONCLUSIONS: MVP is associated with otherwise UCA (IVF), with a prevalence of 6.6%. Bileaflet prolapse appears to be a feature of AMVP, although future studies need to ascertain its independent association. A significant proportion of patients with AMVP received appropriate implantable cardioverter-defibrillator therapies during follow-up.

RyR2 C-terminal truncating variants identified in patients with arrhythmic phenotypes exert a dominant negative effect through formation of wildtype-truncation heteromers.

Gain-of-function missense variants in the cardiac ryanodine receptor (RyR2) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), whereas RyR2 loss-of-function missense variants cause Ca2+ release deficiency syndrome (CRDS). Recently, truncating variants in RyR2 have also been associated with ventricular arrhythmias (VAs) and sudden cardiac death. However, there are limited insights into the potential clinical relevance and in vitro functional impact of RyR2 truncating variants. We performed genetic screening of patients presenting with syncope, VAs, or unexplained sudden death and in vitro characterization of the expression and function of RyR2 truncating variants in HEK293 cells. We identified two previously unknown RyR2 truncating variants (Y4591Ter and R4663Ter) and one splice site variant predicted to result in a frameshift and premature termination (N4717 + 15Ter). These 3 new RyR2 truncating variants and a recently reported RyR2 truncating variant, R4790Ter, were generated and functionally characterized in vitro. Immunoprecipitation and immunoblotting analyses showed that all 4 RyR2 truncating variants formed heteromers with the RyR2-wildtype (WT) protein. Each of these C-terminal RyR2 truncations was non-functional and suppressed [3H]ryanodine binding to RyR2-WT and RyR2-WT mediated store overload induced spontaneous Ca2+ release activity in HEK293 cells. The expression of these RyR2 truncating variants in HEK293 cells was markedly reduced compared with that of the full-length RyR2 WT protein. Our data indicate that C-terminal RyR2 truncating variants are non-functional and can exert a dominant negative impact on the function of the RyR2 WT protein through formation of heteromeric WT/truncation complex.

Management of Inherited Arrhythmia Syndromes: A HiRO Consensus Handbook on Process of Care.

Inherited arrhythmia syndromes are rare genetic conditions that predispose seemingly healthy individuals to sudden cardiac arrest and death. The Hearts in Rhythm Organization is a multidisciplinary Canadian network of clinicians, researchers, patients, and families that aims to improve care for patients and families with inherited cardiac conditions, focused on those that confer predisposition to arrhythmia and sudden cardiac arrest and/or death. The field is rapidly evolving as research discoveries increase. A streamlined, practical guide for providers to diagnose and follow pediatric and adult patients with inherited cardiac conditions represents a useful tool to improve health system utilization, clinical management, and research related to these conditions. This review provides consensus care pathways for 7 conditions, including the 4 most common inherited cardiac conditions that confer predisposition to arrhythmia, with scenarios to guide investigation, diagnosis, risk stratification, and management. These conditions include Brugada syndrome, long QT syndrome, arrhythmogenic right ventricular cardiomyopathy and related arrhythmogenic cardiomyopathies, and catecholaminergic polymorphic ventricular tachycardia. In addition, an approach to investigating and managing sudden cardiac arrest, sudden unexpected death, and first-degree family members of affected individuals is provided. Referral to specialized cardiogenetic clinics should be considered in most cases. The intention of this review is to offer a framework for the process of care that is useful for both experts and nonexperts, and related allied disciplines such as hospital management, diagnostic services, coroners, and pathologists, in order to provide high-quality, multidisciplinary, standardized care.

Les syndromes d'arythmie héréditaires sont des troubles génétiques rares qui prédisposent des personnes en apparence en bonne santé à un arrêt cardiaque soudain et à la mort. L'organisation Hearts in Rhythm Organization est un réseau multidisciplinaire canadien qui regroupe des cliniciens, des chercheurs ainsi que des patients et leurs proches dans le but d'améliorer les soins prodigués aux patients atteints de maladies cardiaques héréditaires et à leur famille, en particulier dans le cas des maladies qui entraînent une prédisposition à l'arythmie et à un arrêt cardiaque soudain et/ou à la mort. Puisque ce champ de recherche évolue rapidement, la mise au point d'un guide pratique et simple à l'intention des professionnels de la santé pour le diagnostic et le suivi des patients enfants et adultes présentant une maladie cardiaque héréditaire serait donc un outil intéressant pour améliorer l'utilisation du système de santé et la prise en charge clinique de ces maladies tout en orientant la recherche à ce propos. La présente synthèse expose les trajectoires de soins faisant l'objet d'un consensus pour sept maladies, dont les quatre maladies cardiaques héréditaires les plus courantes qui prédisposent à l'arythmie. Elle présente aussi des scénarios pour orienter les examens, le diagnostic, la stratification du risque et la prise en charge des patients. Ces maladies sont le syndrome de Brugada, le syndrome du QT long, la cardiomyopathie arythmogénique du ventricule droit et les cardiomyopathies arythmogènes associées, et la tachycardie ventriculaire polymorphe catécholaminergique. En outre, une approche pour la prise en charge de l'arrêt cardiaque soudain, de mort subite inattendue et des membres de la famille immédiate de la personne touchée est proposée. L'orientation vers des cliniques spécialisées en cardiogénétique doit être envisagée dans la plupart des cas. L'objectif est d'établir un cadre de soins qui soit utile pour les experts et les non-experts ainsi que pour les professionnels des domaines connexes, par exemple le personnel de l'administration hospitalière et des services diagnostiques, les coroners et les pathologistes, en vue d'offrir des soins multidisciplinaires normalisés de grande qualité.

Incremental value of the signal-averaged ECG for diagnosing arrhythmogenic cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is currently diagnosed using a combination of clinical features, imaging, electrocardiography, and genetic investigations. An abnormal signal-averaged electrocardiogram (SAECG) is defined as a minor diagnostic criterion by the 2010 Task Force Criteria, but doubts remain about the value of this investigation. OBJECTIVE: We evaluated the utility of the SAECG in diagnosing ARVC using the Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry, a population representative registry of probands with ARVC and relatives, less influenced by referral bias. METHODS: Probands with ARVC and family members from the Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry underwent phenotype review. SAECG parameters were compared individually and in combination between those with varying degrees of ARVC severity and healthy controls (family members of probands with ARVC and unexplained sudden death, free of evidence of cardiac disease). RESULTS: A total of 196 patients with ARVC and 205 controls were included (mean age 44 ± 15 years; 186 of 401 men [46%]). SAECG abnormalities were seen in 83 of 205 controls (40%), 33 of 68 patients with ARVC and mild disease (51%), and 31 of 42 with severe disease (74%). The SAECG associated strongly with imaging abnormalities (major: odds ratio 3.0, 95% confidence interval 1.3-6.9; minor: odds ratio 3.5, 95% confidence interval 0.7-16.5) but not with other aspects of phenotype. Patients carrying pathogenic variants but with minimal phenotype had similar SAECGs to healthy controls (filtered QRS duration 111.2 ± 11.2 ms vs 111 ± 7.6 ms, P = .93; duration of low amplitude signals < 40 µV 32.3 ± 8.9 ms vs 34.2 ± 7.2 ms, P = .32; root mean square of the terminal 40 ms of the filtered QRS complex 43.1 ± 25.2 ms vs 38.2 ± 20.2 ms, P = .38). CONCLUSION: The SAECG appears to be a surrogate marker for structural abnormalities seen on imaging in those with ARVC. Great caution is required in interpreting SAECG findings in those without other corroborating evidence of an ARVC phenotype.

Iatrogenic Arteriovenous Fistula: A Rare Complication of Pacemaker Implantation.

Severe vascular complications associated with pacemaker implantation are rare. Typically, they are overt, and require immediate resolution. We present 2 patients with insidious presentation of arteriovenous fistulae due to pacemaker implantation that were recognized early post-implantation. Both were repaired endovascularly and had good outcomes post-repair. (Level of Difficulty: Intermediate.).

False Positive Troponin Levels due to Heterophil Antibodies in a Pregnant Woman.

Positive troponin test results in peripheral blood can be detected either during myocardial injury or from falsely positive test results. In this report, we present the positive results of a troponin test in a 24-year-old pregnant woman referred to the emergency department with atypical chest pain, and the clinical algorithm that we used to make the correct diagnosis. This patient presented with the same complaint of chest pain at different times while positive troponin levels were detected. In the absence of signs of myocardial injury, we suspected that heterophil antibodies were playing a major role. Further examinations revealed heterophil antibodies that could cross react with the troponin tests in peripheral blood.

Jet length/velocity ratio: a new index for echocardiographic evaluation of chronic aortic regurgitation.

BACKGROUND: Management of aortic regurgitation depends on the assessment for severity. Echocardiography remains as the most widely available tool for evaluation of aortic regurgitation. In this manuscript, we describe a novel parameter, jet length/velocity ratio, for the diagnosis of severe aortic regurgitation. METHODS AND RESULTS: A total of 30 patients with aortic regurgitation were included to this study. Severity of aortic regurgitation was assessed with an aortic regurgitation index incorporating five echocardiographic parameters. Jet length/velocity ratio is calculated as the ratio of maximum jet penetrance to mean velocity of regurgitant flow. Jet length/velocity ratio was significantly higher in patients with severe aortic regurgitation (2.03 ± 0.53) compared to patients with less than severe aortic regurgitation (1.24 ± 0.32, P < 0.001). Correlation of jet length/velocity ratio with aortic regurgitation index was very good (r(2) = 0.86) and correlation coefficient was higher for jet length/velocity ratio compared to vena contracta, jet width/LVOT ratio and pressure half time. For a cutoff value of 1.61, jet length/velocity ratio had a sensitivity of 92% and specificity of 88%, with an AUC value of 0.955. CONCLUSIONS: Jet length/velocity ratio is a novel parameter that can be used to assess severity of chronic aortic regurgitation. Main limitation for usage of this novel parameter is jet impringement to left ventricular wall.

Incidence, risk factors, and outcomes of perioperative acute kidney injury in noncardiac and nonvascular surgery.

BACKGROUND: The aim of this study was to determine the incidence rate, identify the risk factors, and describe the clinical outcome of perioperative acute kidney injury (AKI) in patients undergoing noncardiac, nonvascular surgery (NCS). METHODS: A total of 1,200 adult consecutive patients undergoing NCS were prospectively evaluated. Patients with pre-existing renal dysfunction were excluded. The primary outcome of this study was perioperative AKI defined by the RIFLE (risk, injury, failure, loss of function, and end-stage kidney disease) criteria. RESULTS: Eighty-one patients (6.7%) met the AKI criteria. Multivariate analysis identified age, diabetes, revised cardiac risk index, and American Society of Anesthesiologists physical status as independent predictors of AKI. Patients with AKI had more cardiovascular (33.3% vs 11.3%, P < .001) complications and a higher in-hospital mortality rate (6.1% vs 0.9%, P = .003) compared with patients without AKI. CONCLUSIONS: Several preoperative predictors are found to be associated with AKI after NCS. Perioperative AKI is an independent risk factor for outcome after NCS.

Evaluation of coronary microvascular function and nitric oxide synthase intron 4a/b polymorphism in patients with coronary slow flow.

OBJECTIVE: Slow coronary flow (SCF) is reported to be associated with increased risk of cardiovascular disease. We have used coronary flow reserve measurement by transthoracic Doppler echocardiography to determine coronary microvascular function in patients with SCF and to determine whether the intron 4a/b polymorphism of the eNOS gene influences coronary endothelial function. METHODS: Overall, 96 patients with SCF and 79 controls were enrolled in the study. Coronary flow was quantified according to the thrombolysis in myocardial infarction (TIMI) frame count (TFC) on angiogram. Coronary diastolic peak flow velocities (DPFV) were measured with color Doppler flow mapping at baseline and after dipyridamole infusion. Coronary flow reserve was calculated as the ratio of hyperemic to baseline DPFV. The eNOS 4a/b polymorphism was detected by PCR. Patients with diabetes were excluded from the study. RESULTS: The SCF group was comparable to the control group in terms of demographic and clinical characteristics, except for hemoglobin and HDL-cholesterol levels, TFC of the left anterior descending artery, the circumflex artery, and the right coronary artery; the mean TFC was higher in the SCF group. Hyperemic DPFV and the hyperemic/baseline DPFV ratio were significantly lower in the SCF group when compared with the control group. However, baseline DPFV were similar in both groups. The number of patients with eNOS4 a/a and eNOS4 a/b phenotypes was statistically higher in SCF groups. The frequency of allele 'a' of the eNOS4 gene was also statistically higher in the SCF group. When patients were grouped according to the presence or absence of allele 'a' of the eNOS4 gene, statistically significant differences were found in the TFC of the left anterior descending artery, the circumflex artery; mean TFC; baseline DPFV; and hyperemic/baseline DPFV. Univariate analysis in which eNOS4 b/b was used as the referent group showed that the presence of allele 'a' of the eNOS4 gene significantly predicted SCF (odds ratio: 2.79, 95% confidence interval: 1.32-5.89; P=0.007). In multivariate analysis using a model adjusted for variables with a P value lower than 0.10 in univariate analyses, the presence of allele 'a' of the eNOS4 gene was found to be an independent predictor of SCF (odds ratio: 3.22, 95% confidence interval: 1.28-8.82; P=0.013). CONCLUSION: The presence of allele 'a' may be a risk factor for microvascular endothelial dysfunction and higher TFCs in SCF patients.

Tissue Doppler-derived isovolumic acceleration parameters in organic mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: New, quantitative, reliable and practical echocardiographic parameters are required for grading the severity of mitral regurgitation (MR). Thus, an investigation was made of tissue Doppler imaging (TDI) parameters in MR patients with a preserved left ventricular ejection fraction (LVEF). METHODS: Transthoracic echocardiography was performed in 96 consecutive patients with varying degrees of MR but with a preserved LVEF. In addition, TDI-derived systolic velocities of the mitral and tricuspid annulus were recorded. The results obtained were compared with those from 31 age- and gender-matched healthy controls. RESULTS: The study patients were classified according to MR severity: mild-moderate (n = 65) or severe (n = 31). Although isovolumic myocardial acceleration (IVA) and peak myocardial velocity during isovolumic contraction (IVV) showed similar values in all groups, the acceleration time (AT) was higher in the severe MR group than in mild or moderate MR patients (p < 0.001). The AT cut-off value to predict severe MR was 35 ms (sensitivity 74.2%, specificity 58.5%). CONCLUSION: AT has the potential to differentiate severe MR from non-severe MR in patients with a preserved LVEF. These findings suggest that TDI of the mitral annulus might serve as a novel method for assessing MR severity.

Lower than normal mean platelet volume is associated with reduced extent of coronary artery disease.

BACKGROUND: Extent of atherosclerotic coronary artery disease in patients with stable angina has important prognostic and therapeutic implications. In current models of plaque evolution, thrombocytes play an important role in plaque growth. Mean platelet volume is a readily obtainable marker that was shown to correlate with platelet aggregability in vitro and increased values were demonstrated after acute vascular events. OBJECTIVE: In this study, we investigated the relationship of mean platelet volume and angiographic extent of coronary artery disease in patients with stable angina. METHODS: Past medical records, complete blood count and angiographic data of 267 eligible stable angina patients were reviewed. Angiographic extent of coronary artery disease was evaluated form angiographic data using Gensini score by an expert in invasive cardiology. Mean platelet volume values were obtained from complete blood counts that obtained one day before angiography. Patients were grouped as those within (n = 176) and lower than (n = 62) population-based range for mean platelet volume. Comparison between groups and correlation analysis was performed. RESULTS: There were no linear correlation between total Gensini score and mean platelet volume (p = 0.29), while total thrombocyte count was inversely correlated with mean platelet volume (p < 0.001; r = 0.41). Patients with lower than normal mean platelet volume had significantly lower Gensini score (36.73 ± 32.5 vs. 45.63 ± 32.63; p = 0.023) and three-vessel disease (18% vs. 36%; p = 0.007) compared with those mean platelet volume values within population-based ranges. CONCLUSION: Our findings show no linear relationship exists between mean platelet volume and extent of coronary artery disease, while patients with lower than normal mean platelet volume had reduced extent of coronary artery disease.

Electrocardiographic features of patients with earthquake related posttraumatic stress disorder.

AIM: To analyze electrocardiographic features of patients diagnosed with posttraumatic stress disorder (PTSD) after the Van-Ercis earthquake, with a shock measuring 7.2 on the Richter scale that took place in Turkey in October 2011. METHODS: Surface electrocardiograms of 12 patients with PTSD admitted to Van Ercis State Hospital (Van, Turkey) from February 2012 to May 2012 were examined. Psychiatric interviews of the sex and age matched control subjects, who had experienced the earthquake, confirmed the absence of any known diagnosable psychiatric conditions in the control group. RESULTS: A wide range of electrocardiogram (ECG) parameters, such as P-wave dispersion, QT dispersion, QT interval, Tpeak to Tend interval, intrinsicoid deflection durations and other traditional parameters were similar in both groups. There was no one with an abnormal P wave axis, short or long PR interval, long or short QT interval, negative T wave in lateral leads, abnormal T wave axis, abnormal left or right intrinsicoid deflection duration, low voltage, left bundle branch block, right bundle branch block, left posterior hemiblock, left or right axis deviation, left ventricular hypertrophy, right or left atrial enlargement and pathological q(Q) wave in either group. CONCLUSION: The study showed no direct effect of earthquake related PTSD on surface ECG in young patients. So, we propose that PTSD has no direct effect on surface ECG but may cause electrocardiographic changes indirectly by triggering atherosclerosis and/or contributing to the ongoing atherosclerotic process.

Acute aortic regurgitation with myocardial infarction: an important clue for aortic dissection.

BACKGROUND: Aortic dissection is an important cause of acute chest pain that should be rapidly diagnosed, as mortality increases with each hour this condition is left untreated. The diagnosis can be challenging, especially if concomitant myocardial infarction is present. Echocardiography is an important tool for the differential diagnosis. OBJECTIVES: To stress the importance of recognizing aortic regurgitation for the differentiation of myocardial infarction and aortic dissection. CASE REPORT: An 80-year-old woman was admitted to our hospital with chest pain that was diagnosed as inferior and lateral wall myocardial infarction based on electrocardiographic findings. The diagnosis was reevaluated when aortic regurgitation was detected on echocardiography. Closer inspection of the ascending aorta revealed a dissection flap as the cause of aortic regurgitation. CONCLUSION: Detection of aortic regurgitation in a patient with myocardial infarction and normal valves should prompt the search for a possible aortic dissection, whether or not the dissection flap can be visualized.

An unusual embolic complication of percutaneous coronary artery intervention and simple percutaneous treatment.

Emboli are among the most feared complications of interventional cardiology. Although surgery is needed in most cases for the removal of peripheric foreign body emboli, some may be extracted by percutaneous intervention. We present a case of retrieval of a femoral sheath fragment via contralateral femoral access, wiring of the sheath fragment, and retrieval with an 'anchoring balloon' system.

Acute myocardial infarction after capecitabine treatment: not always vasospasm is responsible.

Capecitabine is an orally available chemotherapeutic agent that is converted to 5-fluorouracil (5-FU) after absorbtion. Capecitabine and its active metabolite, 5-FU, have cardiotoxic effects with reported instances of acute coronary syndromes caused due to coronary vasospasm. However, these agents exert toxic effects on cardiovascular system and beyond vasospasm provacation. We report a 46-year-old patient diagnosed as acute inferior infarction who is treated with capecitabine for 3 months due to metastatic breast carcinoma, in whom thrombotic coronary occlusion was observed in angiography. This case demonstrates that apart from vasospasm, coronary thrombosis could be observed after capecitabine treatment, with a possible direct effect of this drug.