Severe Myocardial Disease Research Articles

Oncologic Emergencies: Immune-Based Cancer Therapies and Complications.

Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse events are most commonly encountered with checkpoint inhibitors and include dermatologic complications, pneumonitis, colitis/diarrhea, hepatitis, and endocrinopathies. Less common irAEs include nephritis, myocardial injury, neurologic toxicity, ocular diseases, and musculoskeletal complications. CRS and CRES are more commonly associated with CAR T-cell therapy. CRS commonly presents with flu-like illness and symptoms resembling sepsis, but severe myocardial and pulmonary disease may occur. Critically ill patients require resuscitation, broad-spectrum antibiotics, and hematology/oncology consultation.

Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach

Idiopathic dilated cardiomyopathy (iDCM) is a primary myocardial disorder with an unknown aetiology, characterized by reduced contractility and ventricular dilation of the left or both ventricles. Naturally occurring canine iDCM was used herein to identify serum proteomic signature of the disease compared to the healthy state, providing an insight into underlying mechanisms and revealing proteins with biomarker potential. To achieve this, we used high-throughput label-based quantitative LC-MS/MS proteomics approach and bioinformatics analysis of the in silico inferred interactome protein network created from the initial list of differential proteins. To complement the proteomic analysis, serum biochemical parameters and levels of know biomarkers of cardiac function were measured. Several proteins with biomarker potential were identified, such as inter-alpha-trypsin inhibitor heavy chain H4, microfibril-associated glycoprotein 4 and apolipoprotein A-IV, which were validated using an independent method (Western blotting) and showed high specificity and sensitivity according to the receiver operating characteristic curve analysis. Bioinformatics analysis revealed involvement of different pathways in iDCM, such as complement cascade activation, lipoprotein particles dynamics, elastic fibre formation, GPCR signalling and respiratory electron transport chain. SignificanceIdiopathic dilated cardiomyopathy is a severe primary myocardial disease of unknown cause, affecting both humans and dogs. This study is a contribution to the canine heart disease research by means of proteomic and bioinformatic state of the art analyses, following similar approach in human iDCM research. Importantly, we used serum as non-invasive and easily accessible biological source of information and contributed to the scarce data on biofluid proteome research on this topic. Bioinformatics analysis revealed biological pathways modulated in canine iDCM with potential of further targeted research. Also, several proteins with biomarker potential have been identified and successfully validated.

Improving pacemaker therapy in congenital heart disease: contractility and resynchronization.

Designed as effective therapy for patients with symptomatic bradycardia, implantable cardiac pacemakers initially served to improve symptoms and survival. With initial applications to the elderly and those with severe myocardial disease, extended longevity was not a major concern. However, with design technology advances in leads and generators since the 1980s, pacemaker therapy is now readily applicable to all age patients, including children with congenital heart defects. As a result, emphasis and clinical interests have advanced beyond simply quantity to quality of life. Adverse cardiac effects of pacing from right ventricular apical or epicardial sites with resultant left bundle branch QRS configurations have been recognized. As a result, and with the introduction of newer catheter-delivered pacing leads, more recent studies have focused on alternative or select pacing sites such as septal, outflow tract, and para-bundle of His. This is especially important in dealing with pacemaker therapy among younger patients and those with congenital heart disease, with expected decades of artificial cardiac stimulation, in which adverse myocellular changes secondary to pacing itself have been reported. As a correlate to these alternate or select pacing sites, applications of left ventricular pacing, either via the coronary sinus, intraseptal or epicardial, alone or in combination with right ventricular pacing, have gained interest for patients with heart failure. Although cardiac resynchronization pacing has, to date, had limited clinical applications among patients with congenital heart disease, the few published reports do indicate potential benefits as a bridge to cardiac transplant.

Radiotherapy for esophageal cancer in Japan

Currently, surgery is the most popular treatment method for esophageal cancer. Radiation is not main treatment but only a supporting one. This situation is now changing because of chemoradiotherapy (CRT). In the 1980s, although most patients treated with radiotherapy were inoperable for extremely advanced or some medical reasons, treatment outcome of surgery was undoubtedly superior to that of radiotherapy. Low-dose rate radiotherapy has many biological benefits. We tried low-dose rate telecobalt therapy (LDRT) as a boost to improve the outcome of radiotherapy for esophageal cancer. However, the LDRT did not improve survival. Since 1990s, studies have demonstrated the effectiveness of CRT using cisplatin and 5-fluorouracil. We made a prospective comparison of surgery and CRT with salvage surgery after recurrence for operable esophageal cancer. Five-year survival rates of 75 CRT patients and 76 surgery ones were 67.5 and 57.7 %, respectively. Twenty-eight patients in the CRT group underwent salvage surgery and 14 survived. Thirty-nine patients in the CRT group (52 %) survived, preserving their esophagus and their QOL was excellent. CRT with salvage surgery should be offered to all operable patients. After CRT, some patients complained severe radiation pneumonitis and myocardial disease. Radiation field should be as small as possible, including the low-dose area. Dose distribution of proton and heavy particle therapies is superior to ordinary radiotherapy. In future, particle beam therapy alone or in combination with photon beam therapy will become widespread as a radiotherapy method during CRT for esophageal cancer.

Global longitudinal strain by two-dimensional speckle tracking echocardiography is closely related to myocardial infarct size in chronic ischaemic heart disease: authors' reply

We read with great interest the letter by Mr Ze-Zhou Song. Mr Song raises important issues on the impact of how deformation parameters such as strain and strain rate are influenced by several conditions and diseases other than myocardial infarction. This has previously been shown in hypertensive and diabetic patients without recognized ischaemic events as well as in other conditions. This aspect will have to be considered when interpreting our results, as well as in the clinical context. In our present study [1], we intentionally did not exclude patients with co-morbidities. We agree with Dr Hoffmann in his reply to a similar request from Mr Song in the European Heart Journal that an exclusion of patients with other conditions would reduce the applicability of the study in clinical practice [2]. The statistical power of our present study [1] was not designed for subgroup analysis, and skewness of other conditions between the groups might therefore have an influence on our results. We have therefore included information on patients' co-morbidity in our paper, and there was no co-morbidity within the reference population. When excluding severe myocardial disease, the impact of other conditions on left ventricular function is limited when compared with the impact of a transmural myocardial infarct [1]. In a clinical context, assessment of regional myocardial function would have to be performed and compared with global left ventricular function in order to distinguish regional disease (such as myocardial ischaemia) from systemic diseases affecting the global left ventricular function in a more homogeneous pattern. We agree with Mr Song that the clinician should consider other conditions resulting in impaired deformation when applying deformation imaging for the assessment of myocardial viability.The main purpose of our present study [1] was to assess the ability of longitudinal speckle tracking strain measurements to distinguish between different levels of myocardial infarct transmurality and to explore the relationship between strain measurements and infarct mass at the territorial and global levels in a chronic ischaemic population [2]. As Mr Song correctly mentions, myocardial motion is complex. The myocardial fibre orientation gradually shifts from a counter-clockwise oblique longitudinal direction in the endocardial layer to near circumferential in the mid-myocardial layer and clockwise oblique longitudinal in the subepicardial layer [3]. This results in three main deformation patterns: longitudinal shortening, circumferential shortening and rotation. Radial thickening is due to a combination of myocyte thickening and shearing of the oblique fibre layers in the subendocardium [4,5]. Assessment of circumferential shortening and radial thickening strains in an infarct population was performed on parasternal short-axis views by Becker et al. [6]. Our present study was not designed for multiple parasternal short-axes imaging, and assessment of short-axis deformation was therefore not feasible. We do agree that a direct comparison of all deformation patterns needs further echocardiographic studies, as present knowledge in this field is limited to MRI (magnetic resonance imaging) studies.

Successful Resuscitation of an ASA 3 Patient following Ropivacaine-induced Cardiac Arrest

A patient with severe myocardial disease and acute-on-chronic renal failure was undergoing a brachial plexus block for formation of an arteriovenous fistula when accidental intravascular injection of ropivacaine resulted in ventricular fibrillation. Cardiopulmonary resuscitation was instituted immediately and the advanced life support algorithm was followed until the return of sinus rhythm. Although, in comparison with bupivacaine, ropivacaine appears to be a safer local anaesthetic agent in the setting of intravenous injection, the emphasis on safety should remain a priority. Awareness of the risk of central nervous system and cardiovascular toxicity and preparation for immediate commencement of resuscitation in the event of toxicity remain of paramount importance.

Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure, in part because of its multifactorial origins. Here we employed comparative transcriptomic methods with quantitative verification of selected transcripts by reverse transcriptase quantitative PCR to characterize the molecular basis of DCM in rats with streptozotocin-induced diabetes of 16-wk duration. Diabetes caused left ventricular disease that was accompanied by significant changes in the expression of 1,614 genes, 749 of which had functions assignable by Gene Ontology classification. Genes corresponding to proteins expressed in mitochondria accounted for a disproportionate number of those whose expression was significantly modified in DCM, consistent with the idea that the mitochondrion is a key target of the pathogenic processes that cause myocardial disease in diabetes. Diabetes also induced global perturbations in the expression of genes regulating cardiac fatty acid metabolism, whose dysfunction is likely to play a key role in the promotion of oxidative stress, thereby contributing to the pathogenesis of diabetic myocardial disease. In particular, these data point to impaired regulation of mitochondrial beta-oxidation as central in the mechanisms that generate DCM pathogenesis. This study provides a comprehensive molecular snapshot of the processes leading to myocardial disease in diabetes.

Antithrombotic Therapy in Atrial Fibrillation-To the Editor

The exclusion of patients with atrial fibrillation from anticoagulant therapy will vary depending on whether they are in a clinical trial or in routine clinical practice. The selective nature of the AFASAK,1 BAATAF,2 SPAF,3 CAFA,4 and SPINAF5 anticoagulant trials was specifically designed to evaluate patients with nonrheumatic atrial fibrillation. Atrial fibrillation coexisting with conditions such as rheumatic mitral stenosis, hyperthyroidism, and severe myocardial disease is well established as an increased risk for thromboembolism and is an absolute indication for anticoagulant therapy.

Clinical profile of patients with Chagas' disease before and during sustained ventricular tachycardia

Sustained ventricular tachycardia was diagnosed in 15 patients undergoing ordinary activity with Chagas' disease seen at our Institute from 1978 to 1989. Palpitations were observed in 11 (66%) of the patients, dyspnea in 7 (46%), atypical chest pain in 5 (33%) and syncope in 2 (13%). Cardiac arrhythmia was detected in 4 (26%) on physical examination. The resting electrocardiogram showed premature ventricular contractions in 13 (86%) patients, ST-T changes in 12 (80%), left axis deviation in 9 (60%) and right bundle branch block in 4 (26%). Chest X-rays showed mild cardiomegaly in 8 (53%) and moderate cardiomegaly in 3 (20%) patients. Mild left ventricular dysfunction was detected echocardiographycally in 1 (10%), moderate in 3 (30%) and severe in 1 (10%) of the 10 patients studied. During sustained ventricular tachycardia, dyspnea was found in 7 of 15 (46%) patients, palpitations in 6 (40%), atypical chest pain in 6 (40%), syncope in 1 (6%), systemic arterial hypotension in 3 (20%) and cardiogenic shock in 2 (13%). The electrocardiographic findings were as follows: mean heart rate was 201 bpm; mean QRS lengthening was 0.16 sec; right bundle branch block plus right axis deviation was seen in 5 of 15 (33%) patients; right bundle branch block plus left axis deviation in 4 (26%); and a positive concordance of all precordial leads in 5 (33%) patients. Based on these findings, we conclude that the majority of patients with Chagas' disease who develop sustained ventricular tachycardia do not have severe myocardial disease, show an uncommon electrocardiographic pattern of this arrhythmia, and most importantly, have a benign clinical course.

High mortality with severe dystrophic cardiac calcinosis in C3H/OUJ mice fed high fat purified diets.

Severe degenerative myocardial disease occurred in female C3H/OUJ mice fed purified diets for 36 weeks; the diet contained 5% or 20% fat as non-hydrogenated soybean oil. Deaths of lactating females of this group (17/35 high fat diet and 7/35 low fat diet animals) were due to sudden cardiovascular collapse. Cardiomegaly with marked atrial and ventricular myocardial mineralization was seen at necropsy. Histologically, the random, myopathic foci were characterized by severe myocardial degeneration, mineralization, and fibrosis. Mural thrombosis, pulmonary arteriosclerosis, and mild myocardial inflammatory cell infiltrates were also present. Pathological changes were similar to those of dystrophic cardiac calcinosis, an incidental necropsy finding in certain mouse strains.

Long-standing bidirectional tachycardia in a patient with hypokalemic periodic paralysis

Bidirectional tachycardia is an uncommon arrhythmia that usually occurs in aged persons with severe myocardial disease or digitalis intoxication, and carries a poor prognosis. This is a report of a young woman with familial hypokalemic periodic paralysis, who has a 13-year history of asymptomatic bidirectional tachycardia in the absence of organic heart disease or digitalis intoxication. Association of periodic paralysis and bidirectional tachycardia in this case and four previously reported cases suggests a strong relationship between this arrhythmia and potassium.

Results of percutaneous catheter valvuloplasty for calcified aortic stenosis in the elderly.

Percutaneous catheter valvuloplasty was performed in 37 patients between 60-88 years of age (mean age 74.5 years): 16 of these patients were in functional class IV, with pulmonary oedema at the time of the procedure. A good haemodynamic result was obtained in 32 patients, but 3 of them had to be operated upon subsequently, because of persistence of their symptoms. Two successfully dilated patients died in the hospital, one of cardiac failure following myocardial dysfunction caused by multiple infarcts which had no relation to the aortic dilatation, the other of neurological complications after dilatation. Thus, the primary success rate was 27/37 (73%). The first 10 patients with good initial results have been followed up for more than 6 months. The functional result has been maintained in 8 cases with moderate myocardial dysfunction (left ventricular ejection fraction 0.41 to 0.7), one with restenosis at Doppler assessment. Two patients with severe myocardial dysfunction (left ventricular ejection fraction 0.22 and 0.25) had recurrent cardiac failure, with valvular restenosis in one case. One of them died at home. Percutaneous aortic valvuloplasty is therefore an effective means of treating calcified aortic stenosis in elderly patients. The benefits of this procedure have been maintained for as long as 6 months provided myocardial dysfunction was moderate. At its present stage of development, the technique allows only partial reduction of the aortic stenosis, which may explain the absence of long-term improvement in patients with severe myocardial disease.

Left bundle branch block with right axis deviation: A marker of congestive cardiomyopathy

Three patients with primary congestive cardiomyopathy (COCM), complete left bundle branch block (LBBB) and right axis deviation in the standard leads are described. Review of 50 additional patients from the literature since 1950 indicates that the uncommon combination of LBBB and RAD is a marker of severe myocardial disease, especially COCM. The mechanism of production of this electrocardiographic pattern appears to be diffuse conduction system involvement in advanced myocardial disease.

Clinical recognition of giant left ventricular aneurysm

The noninvasive diagnosis of left ventricular aneurysm has markedly improved with gated blood pool scintigraphy. However, in patients with giant anterior ventricular aneurysms, the gated blood pool scintigram performed in two standard views (anterior and 40 degree left anterior oblique) may incorrectly suggest ischemic cardiomyopathy. We retrospectively identified five patients who underwent resection of a ventricular aneurysm over a 2 1 2 year period and who had preoperative scintigraphic studies that appeared to show severe diffuse left ventricular dysfunction. Contrast ventriculography demonstrated preserved wall motion in septal, inferior and lateral segments not seen by gated blood pool scintigraphy and showed extraordinarily large anterior aneurysms. M-mode or two-dimensional echocardiograms showed intact posterior wall function in all patients, suggesting severe regional myocardial disease rather than global dysfunction. Two-dimensional echocardiography showed additional segments with preserved function as well as discrete aneurysms in all patients. We conclude that gated blood pool scintigraphy, when performed in two standard views, may fail to correctly diagnose some patients with very large anterior wall aneurysms. M-mode echocardiography, two-dimensional echocardiography and additional scintigraphic views that visualize the posterior portions of the left ventricle improve noninvasive diagnosis of patients with resectable giant left ventricular aneurysms.

Spectrum of congestive heart failure late after aortic valve or mitral replacement: Differentiation of valvular versus myocardial cause by radionuclide ventriculogram-ejection fraction

Heart failure (CHF) appearing late after aortic (AV) or mitral valve (MV) replacement (R) may be due to mechanical factors such as prosthetic or native valve dysfunction, or due to myocardial disease. We studied 41 patients who developed CHF late (6 weeks to 11 years) after AVR or MVR with gated blood pool scan (RNV) to analyze the spectrum of ejection fraction (EF) and its clinical correlates. Of the 17 patients who developed CHF after AVR, 10 had RNV EF greater than 0.5 (all of whom had severe valve or prosthetic dysfunction as the primary cause of CHF) and seven had EF less than 0.5 (five with severe myocardial disease and two with prosthetic dysfunction). Of the 24 with CHF after MVR, 13 had RNV EF greater than 0.5. In contrast to post-AVR patients, only 8 of the 13 patients had mechanical causes of CHF (seven prosthetic dysfunction and one constrictive pericarditis). Of the 11 patients after MVR with EF less than 0.5, nine had severe myocardial disease and two had prosthetic dysfunction. Thus (1) reduced EF in patients with CHF-after AVR or MVR suggests myocardial disease as the basis for CHF, and (2) normal EF implies a mechanical cause of CHF after AVR but may be associated with either myocardial or mechanical factors after MVR.

Polymorphous ventricular tachycardia: Clinical features and treatment

Thirty-four cases of ventricular tachyarrhythmia characterized by polymorphy of the QRS complexes with changing R-R intervals and a heart rate of 150 to 300 beats/min, termed polymorphous ventricular tachycardia, are described. The factors involved in the appearance of this arrhythmia were the administration of antiarrhythmic drugs (quinidine 22 patients, procainamide 5 patients, ajmaline 1 patient), antianginal drugs (prenylamine [Synadrin] 4 patients) and antidepressant drugs (thioridazine 1 patient). Twenty-one patients were treated for premature ventricular complexes, three for chronic recurrent ventricular tachycardia, six for atrial flutter and fibrillation, three for anginal pain and one patient for mental depression. All patients except one had a drug-induced prolonged corrected Q-T interval before the appearance of polymorphous ventricular tachycardia. Most of the patients with this arrhythmia were considered to have severe myocardial disease. Lidocaine and electric cardioversion were administered to all patients, but were effective only in seven patients whose tachycardia occurred in short, single episodes. The most effective treatment (17 patients) was temporary ventricular pacing at rates ranging from 100 to 140 beats/min. Intravenous isoproterenol proved to be successful in another 10 cases. It is concluded that patients with severe myocardial involvement receiving antiarrhythmic drugs for premature ventricular complexes, especially the multiform variety, are at high risk for the development of polymorphous ventricular tachycardia.

Disopyramide: Serum level and arrhythmia conversion

The response of arrhythmias to oral disopyramide in relation to its serum levels has been documented. Disopyramide (100 mg.) was given orally, 6 or 8 hourly, to 16 patients with coronary or hypertensive heart disease who developed acute but stable cardiac arrhythmias (20 episodes) which persisted, despite bed rest and sedation with intravenous diazepam or diamorphine. Blood was taken when arrhythmia conversion was observed and the serum disopyramide levels were estimated by gas chromatography. Over-all control of arrhythmias was achieved in 13 (82 per cent) patients within 24 hours. Disopyramide-serum levels were as follows: effective for atrial arrhythmias, 2.80 to 3.18 mug per milliliter, and 3.27 to 7.48 mug per milliliter for ventricular; mean effective levels for all arrhythmias, 3.69 mug per milliliter; mean ineffective levels, 2.39 mug per milliliter (p less than 0.01). Side effects (prolongation of PR and QTc, fall of diastolic BP, urine retention) were observed with serum levels of 3.61 to 7.48 mug per milliliter (mean, 5.54 mug per milliliter) but they were not troublesome clinically. It is concluded that disopyramide is effective and safe with serum levels ranging from 2.39 to about 3.60 mug per milliliter, and this can be maintained with 100 mg., 8 hourly. The drug, however, should be given with caution to patients with severe myocardial disease or low arterial pressure and in the presence of an abnormal ECG.

Right ventricular volume in congenital heart disease

Methods for angiographic determination of right ventricular volume were compared in right ventricular cast studies and in vivo using a semiautomated Simpson's rule, elliptical and rectangular cross sections and a simple geometric model, a prism with a triangular base. In cast studies excellent correlation coefficients were obtained for all three methods ( r = 0.97 to 0.98). In vivo, excellent linear correlation was obtained when the methods were compared ( r = 0.98 to 0.99, P < 0.001). Normal mean right ventricular volumes (70 patients) in milliliters per square meter±1 standard deviation were: end-diastolic volume 64 ± 15, end-systolic volume 25 ± 8 and stroke index 39 ± 11; ejection fraction was 0.61 ± 0.08. Normal mean left ventricular end-diastolic and end-systolic volumes (77 patients) were lower (59 and 19, respectively), and ejection fraction was higher (0.68). Stroke index was the same. Other results showed decreased mean end-diastollc and end-systolic volumes and stroke index, increased ejection fraction ( P < 0.001, < 0.025, < 0.025 and < 0.005, respectively) in 34 patients with pulmonary stenosis, and increased mean end-diastolic and end-systolic volumes and stroke index ( P <0.001, <0.050, <0.001, respectively) in 11 patients with an atrial left to right shunt. In both groups postoperatively, as well as in patients with a ventricular septal defect, tetralogy of Fallot or myocardial disease, mean volumes and ejection fraction were normal. We conclude that a geometric model can be used to determine right ventricular volume with accuracy. In children, the right ventricle can adapt reversibly to chronic increases in afterload and preload; it is not necessarily overloaded by a ventricular septal defect or tetralogy of Fallot, and it is relatively unaffected by severe myocardial disease.

Systolic time intervals in constrictive pericarditis and severe primary myocardial disease

The systolic time intervals were measured in 18 patients with CP and in 10 patients with COCM. The results in the two groups were compared with each other and then compared with the ejection fraction measured by left ventriculography in 13 patients with CP and in all patients with COCM. Ejection fraction was below 0.45 in patients with severe COCM and above this in CP. PEP SEP ratio was closely correlated with ejection fraction and this could be predicted from a regression equation. The ratio PEP SEP distinguished between CP and COCM in patients with severe heart failure.

2-O Interval as an Indicator of Left Atrial Pressure

The time interval between the aortic closure sound and O point or the apexcardiogram (2-O) interval) was determined in a group of 38 normotensive patients and correlated with the mean left atrial or pulmonary capillary wedge pressure. Twenty-three patients had an elevated left atrial pressure and an average 2-O interval of 0.076 seconds. Fifteen patients had a normal left atrial pressure with an average 2-O interval of 0.10 seconds. Both normal and abnormal left atrial pressures occurred at 2-O intervals of 0.08 seconds or more. A 2-O interval of 0.07 seconds or less was associated with a left atrial pressure of 18 mm Hg or more. On the basis of this study, it is concluded that the 2-O interval is a simple, accurate, non-invasive method of predicting an elevated left atrial pressure in normotensive patients with severe coronary artery or myocardial disease.