Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.

Detection of LV apical thrombus by three-dimensional transesophageal echocardiography.

INTRODUCTION: Patients with apical myocardial infarction are at higher risk of developing left ventricular (LV) thrombi. Standard transesophageal echocardiography (TEE) is commonly used in assessing cardiac source of embolic cerebrovascular accident (CVA). Contrast-enhanced transthoracic echocardiography (TTE) improves sensitivity for thrombus detection compared with noncontrast TTE, and however for LV apical thrombi, contrast-enhanced magnetic resonance imaging (MRI) and/or contrast-enhanced computed tomography (CT) outperform both TTE and TEE in some studies. CASE: A 67-year-old man with history of prior myocardial infarction (MI), four-vessel coronary artery bypass surgery, congestive heart failure with LV ejection fraction of 30%, and diabetes mellitus presented to our facility with acute right occipital-parietal stroke and recent history of left lower extremity ischemia. Head and neck MRI and MR angiography found multiple posterior circulation infarcts suggestive of cardio-embolic etiology. TTE image quality was suboptimal even after contrast use to evaluate for LV thrombus, and due to renal insufficiency, MRI or CT was precluded and 3DTEE identified large LV apical thrombus with mobile components. CONCLUSION: 3DTEE may increase the detection of LV apical thrombi as well as evaluating its characteristics by live imaging as well as by offline reconstruction. TEE may be a useful diagnostic modality, especially in patients with decreased renal function, where iodinated contrast for cardiac CT or Gadolinium for MRI may be contraindicated. Multimodality imaging studies may further prove the utility of 3D echocardiographic imaging in the detection of LV apical thrombus.

Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial.

OBJECTIVE: The aim of this study is to evaluate the preventive effects of carvedilol on doxorubicin-induced cardiotoxicity. METHODS: In this trial, 70 female patients with breast cancer who were candidates to receive doxorubicin were enrolled, from which 30 were selected randomly to receive carvedilol 6.25 mg daily during chemotherapy, with the rest receiving placebo as the control group. Both groups were evaluated 1 week before and 1 week after chemotherapy by measuring the left ventricular ejection fraction and strain/strain rate. RESULTS: Data analysis showed that the case group presented no significant reduction in strain and strain-rate parameters after intervention, while there was a significant reduction in these parameters in the control group (all p values <0.001). Also, the mean differences of strain parameters in the case group were significantly less than in the control group in all evaluated heart walls (basal septal strain, p = 0.005, basal lateral strain, p = 0.001, basal inferior strain, p < 0.001, and basal anterior strain, p < 0.001); the same was true for the strain-rate parameters (the p values for basal septal, basal lateral, basal inferior and basal anterior strain rate were 0.037, 0.037, 0.002 and <0.001, respectively). CONCLUSION: This study shows that carvedilol can prevent doxorubicin-induced cardiotoxicity. Whether this prophylaxis should be considered as the preferred method needs further investigation.

Erythropoietin Reduces Post-PCI Arrhythmias in Patients With ST-elevation Myocardial Infarction.

BACKGROUND: Arrhythmia is the foremost cause of sudden death after myocardial infarction (MI). Animal models have recently shown that erythropoietin (EPO) can reduce the incidence of arrhythmia after MI. METHODS: We investigated the effects of administrating 33,000 IU EPO on the occurrence of post-MI arrhythmia in 40 patients with ST-elevation MI who were randomly assigned in either EPO or placebo groups. Arrhythmias were blindly documented using full 12-lead configuration during 24 hours after percutaneous coronary intervention (PCI) by a cardiologist. Afterward, CK-MB, hematologic, and hemodynamic data were examined within 2 weeks after MI. RESULTS: A comparison made between the 2 groups showed significant differences in the incidence of arrhythmias (20% in EPO group and 35% in placebo group, P = 0.043). However, no significant differences in type of arrhythmias were observed between the groups. There was no significant difference between levels of CK-MB in the 2 groups during 24 hours (P = 0.186). Hematologic and hemodynamic data showed no significant changes 2 weeks after PCI. CONCLUSION: High-dose administration of EPO in patients with ST-elevation MI who have been treated by primary PCI and standard antiplatelet therapy reduces the occurrence of arrhythmias. For clinical interpretation of the results, further well-designed trials are required.

Novel echocardiographic parameters in pulmonary hypertension assessment and the relationship between echocardiography and 6-minute walking test.

Pulmonary artery stiffness (PAS) has been shown to be related to pulmonary artery pressure in patients with pulmonary artery hypertension (PAH). The aim of this study was to determine the correlation between functional capacity and echocardiographic indices of PAS in patients with PAH. This cross-sectional study was performed on patients with PAH who were confirmed by right heart catheterization and referred to Imam Reza PAH clinic for routine follow-up between November 2019 and January 2020. All patients underwent echocardiography and the maximum Doppler frequency shift, pulmonary acceleration time, peak velocity of the pulmonary flow, and velocity time integral, as well as PAS, were measured. All patients performed a 6-minute walk test. Fifty patients with a mean age of 41.90 ±â€…14.73 years old participated in this study. The majority of the patients were female (74%). The most common cause of PAH was idiopathic (74%). There was a significant correlation between PAS and pulmonary artery systolic pressure (r = 0.302, P = .041), second pulmonary valve pulse Doppler velocity (V2) (r = -0.461, P = .003), time from onset of pulmonary flow ejection to V2/first pulmonary valve pulse Doppler velocity (r = -0.311, P = .037) and Z3 ratio (r = -0.346, P = .023). There was no significant correlation between PAS and 6-minute walk test, pulmonary vascular resistance, and tricuspid annular plane systolic excursion (P > .05). There was a significant correlation between V2 and pulmonary vascular resistance (r = 0.359, P = .049). PAS and first pulmonary valve pulse Doppler velocity are simple, noninvasive, available tools for the evaluation of pulmonary vascular beds and diagnosis of presymptomatic clinical status in patients with PAH.

Aortic propagation velocity in predicting coronary artery disease: A systematic review and meta-analysis.

INTRODUCTION: Coronary artery disease (CAD) and its outcome, myocardial infarction, is yet a significant etiology of mortality and morbidity nowadays. The aortic propagation velocity (APV) can be a simple, straightforward and novel echocardiographic index for the risk stratification in the evaluation of CAD. In this meta-analysis, we evaluated the predictive role of APV in CAD. MATERIAL AND METHODS: Relevant electronic bibliographies (PubMed, ScienceDirect, Scopus, EMbase, the Cochrane library) were explored. Related reports were selected according to the inclusion and exclusion criteria. Meta-analysis was performed using the Comprehensive Meta-analysis 2.0 software. RESULTS: Eventually, 5 articles met the inclusion criteria and included in the meta-analysis. Five studies with 490 patients reported the APV mean in CAD and non-CAD groups. A random-effect model was used and the pooled findings demonstrated a significant higher APV in non-CAD group compared to CAD group (SMD: 2.39, 95% CI: 1.70-3.07, P < .001, I2: 84%, Q: 19.03). The diagnostic value of APV in predicting CAD showed 86.3% sensitivity (95% CI: 74-91, P value < .001, I2: 65%, Q: 8.53, P value: .03) and 83.8% specificity (95% CI: 69-94, P value < .001, I2: 60%, Q: 9.89, P value: .01). CONCLUSION: There was a predictive role of APV in CAD with suitable specificity and sensitivity. Moreover, aortic distensibility and aortic strain were significantly different in CAD and non-CAD patients. APV could be used as a good noninvasive tool for screening CAD.

An incidental finding of unroofed coronary sinus during angiography confirmed by 3D echocardiography; A case report.

Unroofed coronary sinus (UCS) is an uncommon congenital heart anomaly and the most unusual type of atrial septal defect. This report presents a 71-year-old female with palpitation and dyspnea following an emotional stress, who was referred for ablation of typical atrial flutter. Finally diagnosed with a partially unroofed CS causing a bidirectional shunt.

Infective Endocarditis: Clinical Characteristics and Echocardiographic Findings.

Purpose: Infective endocarditis (IE) remains a disease with high morbidity and mortality. The aim of this study was to determine the clinical characteristics and echocardiographic features of patients with IE. Methods: We analyzed patients with either definitive or probable diagnosis of IE who were hospitalized in a teaching hospital in Mashhad, Iran between June 2011 and January 2020. Patients who survived were followed up by echocardiography for at least 6-month after hospital discharge. Results: A total of 82 cases with IE were included of which 62 (75.6%) received definitive diagnosis. The mean age was 39.7 ± 18.7 years and 52 (63.4%) were male. The most common preexisting structural cardiac abnormality that predispose patients to IE were congenital heart diseases (28 %) of which bicuspid aortic valve was more common (n = 12, 14.6%), followed by ventricular septal defect (n = 9, 11%) and Tetralogy of Fallot (TOF) (n = 2, 2.4%). Three (3.6 %) cases had rheumatic heart disease and 12 (14.6 %) were injecting drug users. The most common causative pathogen was Staphylococcus aureus, detected in 7 (19.4%) cases. Follow-up echocardiography revealed right or left ventricular failure in 10 (12.1%) cases. Cardiac complications occurred in 41 (50%) cases and systemic complications in 63 (76.8%). All-cause mortality was 41.5% (n = 34) and 6 (18.1%) patients died due to cardiovascular complications. Conclusions: The short- and long-term prognosis in IE was poor and the predictors for in-hospital and 1-year mortality were defined as heart failure and septic shock. Congenital heart disease and intravenous illicit drug using (IVDU) were the most common predisposing condition which may necessitate a revision in the IE prophylaxis recommendations.

Two cases of parachute tricuspid valve confirmed by three-dimensional echocardiography.

BACKGROUND: Parachute tricuspid valve is a rare congenital malformations explained in the literature. In most cases, this malformation coexists with other congenital defects. The importance of this condition depends on its functional consequences. CASE REPORT: First case was a 52-year-old female patient presented with palpitation. She had a history of paroxysmal supraventricular tachycardia. Transthoracic echocardiography revealed large secundum type atrial septal defect and all the tricuspid valve leaflets appeared to be connected to a single calcified papillary muscle in right ventricle suggestive of parachute tricuspid valve. Echocardiography showed severe right ventricle and right atrial enlargement, and moderate to severe tricuspid regurgitation without significant tricuspid stenosis. Another case was a 30-year-old female patient referred for echocardiography prior to her breast cancer chemotherapy. Transthoracic echocardiography revealed a right ventricle with an unusual fusion of papillary muscles resulting in a single calcified head for the attachment of all tricuspid leaflets. These findings were suggestive of a parachute-like tricuspid valve. Other data were mild to moderate tricuspid regurgitation without any stenosis, and normal right ventricle size and function. In both cases, parachute tricuspid valve was confirmed by three dimensional echocardiograph. CONCLUSION: In our first case, parachute tricuspid valve was associated with atrial septal defect, although in the second case, no associated anomaly was detected, a condition not previously reported in the literature. In both cases, parachute tricuspid valve was not associated with tricuspid stenosis. Based on other published cases, parachute involvement of the tricuspid valve is less often reported than cases involving the mitral valve. Additionally, the associated consequences in tricuspid valve position such as tricuspid stenosis seem to be less significant than cases involving mitral valve. It is recommended that in patients with tricuspid valve involvement, parachute anomaly should be considered as a possible rare cause.

Situs Inversus with Levocardia and Congenitally Corrected Transposition of Great Vessels in a 35 year old Male: A Case report.

Situs inversus with levocardia and congenitally corrected transposition of the great arteries represents a relatively very rare congenital condition and most patients are diagnosed in infancy or early age. This case report describes a 35-year old man with congenitally corrected transposition of the great arteries which presented with a five month history of exertional dyspnea. A diagnosis was confirmed by transesophageal echocardiogram, showing situs inversus, levocardia, atrioventricular and ventriculoarterial discordance. He underwent physiologic repair, and was discharged thirty five days after the operation, in a good general condition. Although management of the corrected transposition of the great arteries patients remains controversial, the recommendation is that physiologic repair may be the procedure of choice for some patients, particularly complicated cases.

Echocardiographic characteristics of isolated left ventricular noncompaction.

BACKGROUND: Although isolated left ventricular noncompaction (ILVNC) has been described almost two decades ago, our knowledge about its diagnosis, presentation, echocardiographic features and clinical outcome is sparse. We aimed to assess the echocardiographic and clinical characteristics of ILVNC in a group of patients referred to our center. METHODS: Patients who were referred to a tertiary referral center, affiliated with Mashhad University of Medical Sciences, with primary diagnosis of dilated cardiomyopathy underwent comprehensive echocardiographic evaluation. The diagnosis of ILVNC was made based on the presence of two-structural layer in myocardium; ratio of noncompacted to compacted layers more than 2, and excessive trabeculation in the left ventricle. RESULTS: Final diagnoses of ILVNC were made in 42 patients. Mean age of patients was 32.9 ± 15.6 years (ranging from 9 to 70 years). Females comprised a higher proportion of patients (61.9%) and shortness of breath was the most reported symptom among patients (47.6%). Non-compacted layers were detected in inferior and lateral segments of apex in 97.6% of patients. A total of 26 (61.9%) patients had left ventricle (LV) dysfunction (defined as ejection fraction less than 50%). The only factor that showed significant association with LV dysfunction was the number of affected segments with noncompaction (P = 0.008). Reduced ejection fraction was not associated with either age or sex (P = 0.437 and P = 0.206, respectively). CONCLUSION: Based on the result of the current study, it can be suggested that apex of the heart is the most common site of noncompaction and increasing numbers of affected segments might be associated with LV dysfunction.

Congenital coronary artery anomaly simulating a ventricular septal defect.

Anomalous origin of the circumflex artery of the right sinus of Valsalva is a rare finding which may be present with other cardiac malformations. A 19-year-old man presented with syncope. A transthoracic echocardiogram revealed discrete subaortic stenosis with a small defect just below the aortic valve, suggesting a ventricular septal defect. Transesophageal echocardiography showed anomalous origin of the circumflex artery from the right sinus of Valsalva. This was confirmed by coronary angiography. The patient underwent successful web resection without concomitant coronary surgery. Failure to demonstrate a coronary artery anomaly can be misleading for surgeons and perilous for patients.

Long-term clinical outcomes of the left ventricular thrombus in patients with ST elevation anterior myocardial infarction.

BACKGROUND: This study was performed to determine the size of left ventricular thrombus (LVT), risk of systemic embolization and response to medical treatment during 18 months of follow up in the patients with anterior-ST elevation myocardial infarction (aSTEMI). METHODS: This cross-sectional study was performed on thirty-five patients with anterior myocardial infarction (MI), in Emam Reza Hospital and Ghaem Hospital, Mashhad, Iran, from August 2008 to January 2011. Warfarin was prescribed for all the patients. Transthoracic echocardiographic study was performed on the 1st, 2nd, 4th, 6th, 12th and 18th months. Outcomes included rate of death, MI, stroke, systemic embolization, major bleeding and change in thrombus size following treatment. RESULTS: The resolve rate of clot on the 2nd, 4th, 6th, 12th and 18th months was 64.7, 86.6, 81.4, 81.4 and 100 percent, respectively. In five patients with complete clot resolution, clot reformation occurred after warfarin discontinuation. In these patients, left ventricular ejection fraction (LVEF) improvement was poor. During the study period, five patients died due to severe heart failure. One patient developed hematuria whereas non-experienced thromboembolic events. The mean LVEF at study initiation was 30.8 ± 0.92%, which improved to 42 ± 0.84% (P < 0.05) at the end. CONCLUSION: All LVT was resolved with a combination therapy of antiplatelet and warfarin without any thromboembolic event. In patients with a poor improvement in the LV function, due to the risk of LVT reformation, lifelong warfarin therapy was recommended.

A case of left atrial myxoma with unusual tumor vascularity.

A 69-year-old woman presented with a 2-week history of chest pain and mitral and aortic valve replacement 15 and 5 years earlier. Transthoracic echocardiography revealed a well-seated monoleaflet mitral valve and a bileaflet aortic valve with normal function. Cardiac catheterization showed 3-vessel coronary artery disease and an abnormal cluster of new vessels derived from the left atrial circumflex and posterior ventricle branches. Two- and 3-dimensional transesophageal echocardiography identified a semi-mobile oval left atrial mass with multiple internal cystic spaces, attached to the fossa ovalis region in the interatrial septum. The mass was resected. The pathological diagnosis was atrial myxoma.

Carcinoid heart disease and the utility of 3D trans-thoracic and trans-esophageal echocardiography: Two clinical cases.

Carcinoid tumors are rare neuroendocrine malignancies. We present two cases of metastatic carcinoid tumors, complicated by carcinoid syndrome and by cardiac valve involvement. Carcinoid syndrome is characterized by secretory diarrhea, episodic flushing, and bronchospasm. Cardiac involvement occurs in up to 50% of patients with metastatic carcinoid tumors which commonly causes abnormalities of the right sided valves. Echocardiography is the best available and non invasive technique for diagnosis. Characteristic features of carcinoid heart disease are thickened, shortened, retracted, and fixed or partially fixed valve leaflets. Three-dimensional (3D) echocardiography provided an en face view of pulmonary and tricuspid valve, not obtainable by two-dimensional echocardiography, and improved delineation of the relationship between these structures and cardiac chambers.

Frequency of ischemic mitral regurgitation after first-time acute myocardial infarction and its relation to infarct location and in-hospital mortality.

BACKGROUND: Ischemic mitral regurgitation (IMR) is a common complication after acute myocardial infarction (AMI). We aimed to investigate the frequency of IMR following first-time AMI and its association with infarct location, in-hospital mortality, and complications. METHODS: From September 2011 to November 2012, all patients with a diagnosis of first-time acute ST-elevation MI were enrolled in the study. Patients with previous MI and heart failure, organic mitral valve disorders, and previous mitral surgery were excluded from the study. The patients' baseline characteristic, echocardiographic parameters, and complications were recorded. The frequency of IMR after AMI and its relation to infarct location and in-hospital mortality were evaluated. RESULTS: Altogether, 250 patients (180 male) at a mean age of 60.21 ± 12.90 years were studied. IMR was detected in 114 (45%) patients. There was no association between the presence of MR and gender, systemic hypertension, smoking, diabetes mellitus, or body mass index; however, serum LDL-cholesterol and triglyceride levels were significantly higher in the patients with IMR . The most frequent territory of MI was anterior in the patients without MR, while the anterolateral territory was the most common one in the patients with IMR. The patients with IMR had more reduced left ventricular ejection fraction, more elevated left ventricular end-diastolic pressure, and higher pulmonary arterial pressure (p values < 0.001, < 0.001, and < 0.001, respectively). Stage III diastolic dysfunction was more frequent in the patients with IMR. All the deaths occurred in the IMR patients, who also had more complicated AMI. CONCLUSION: IMR following AMI is highly prevalent, and it complicates about half of the patients. Regarding its relation to the AMI complications, assessment of the MR severity is necessary to make an appropriate decision for treatment.

Serum small dense low-density lipoprotein concentrations are elevated in patients with significant coronary artery stenosis and are related to features of the metabolic syndrome.

Serum small dense low-density lipoprotein (sd-LDL) concentrations were measured in patients with angiographically defined coronary artery disease (CAD) and compared to concentrations in healthy subjects. Five hundred and seventy patients with stable CAD were divided into CAD- and CAD+ based on angiography. Patients in whom stenosis was <50 % in diameter were classified as having a 'normal' angiogram (CAD-), otherwise the patients were allocated to the CAD+ group. The CAD+ group was further subcategorized into single-, double- and triple-vessel disease (VD). Serum sd-LDL concentrations were significantly lower in controls compared with CAD+ and CAD- patients (P < 0.001). Moreover, CAD+ patients had higher concentrations of sd-LDL than CAD- patients (P < 0.01). sd-LDL levels were not significantly associated with severity of CAD defined by the number of stenosed coronary arteries (P = 0.245). All participants were also categorized into subgroups with or without metabolic syndrome. Subjects with metabolic syndrome had higher levels of sd-LDL than subjects without metabolic syndrome (P < 0.01). Multiple linear regressions showed that in CAD patients, triacylglycerol, total-cholesterol, body mass index, and waist circumferences were the most important determinants of serum sd-LDL concentrations. We found that sd-LDL levels were significantly higher in patients presenting with symptoms of CAD. Moreover, patients with significant stenosis of their coronary arteries (>50 % stenosis) had higher levels of sd-LDL compared to patients without significant lesions.

Incidental Finding of Cor Triatriatum Sinistrum in a Middle-Aged Man Candidated for Coronary Bypass Grafting (with three-D imaging).

Cor triatriatum sinistrum is a rare congenital cardiac malformation, accounting for about 0.1-0.4% of all congenital heart diseases and characterized by the presence of a fibromuscular membrane that subdivides the left atrium into two chambers in the classical form. While classic cor triatriatum in most patients can be observed during the neonatal period or early infancy, it is very rare in adults.We herein present an incidental finding of cor triatriatum sinistrum in a middle-aged man with coronary artery disease scheduled for coronary artery bypass graft surgery. The patient was admitted for exertional dyspnea and chest pain of a three-month duration. He had a past medical history of mild hyperlipidemia and mild hypertension. Transthoracic two-D echocardiography (TTE) demonstrated a visible presence of a membranous band in the mid portion of the left atrium with obvious obstruction by color and Doppler flow measurements, confirmed by three-D echocardiography. Selective coronary angiography also revealed a severe ostioproximal stenosis of the left anterior descending artery of up to 99%.On-pump coronary artery bypass grafting was performed without complications, during which the anastomosis of the left internal mammary artery to the left anterior descending artery and the removal of the membrane were done.

Prooxidant-anti-oxidant balance is not associated with extent of coronary artery disease.

OBJECTIVE: We have measured the pro-oxidant-antioxidant-balance (PAB) levels in patients with defined coronary artery disease (CAD) and compared them with concentrations in healthy subjects. DESIGN AND METHODS: Based on angiography results, 400 patients with stable CAD were divided into CAD- and CAD+, this being further subcategorized into groups with single-, double- and triple-vessel disease (VD). RESULTS: The mean PAB values in the healthy subjects, was significantly lower than for other groups (P<0.001). In CAD- patients, PAB levels were 123.2 ± 43.9, which was not statistically different compared to groups with SVD, 2VD and 3VD (P>0.05). In the CAD+ group, PAB values in 1VD, 2VD and 3VD were not significantly different among patients with SVD, 2VD and 3VD (P>0.05). CONCLUSIONS: In conclusion, we found higher levels of oxidative stress in CAD+ patients compared to healthy subjects. The oxidation level was not related to measures of the extent of CAD such as number of stenosed vessels.