Cardiovascular magnetic resonance in mild to moderate clozapine-induced myocarditis: is there a role in the absence of electrocardiographic and echocardiographic abnormalities?

Clozapine is an atypical, neuroleptic medication that can cause myocarditis. While the "gold standard" for diagnosis of myocarditis is perceived to be via myocardial biopsy, cardiovascular magnetic resonance (CMR) has also proven its utility in this respect, primarily through its ability to detect myocardial scar by late-gadolinium enhancement (LGE). Until recently, however, clozapine-induced myocarditis specifically has not been known to be associated with LGE on CMR. In that particular case, LGE was demonstrated in a patient with clozapine-induced myocarditis. However, quite important, that patient also had specific abnormalities on the electrocardiogram (ECG) and echocardiogram that corresponded to the area of LGE demonstrated by CMR. We highlight a case series of three patients with clozapine-induced myocarditis and provide a literature review to discuss and critically appraise the true incremental diagnostic value of CMR in such patients with normal ECG and echocardiography.

The association of atrial tachyarrhythmias with isolated atrial amyloid disease: preliminary observations in autopsied heart specimens.

OBJECTIVE: Isolated atrial amyloidosis (IAA) is associated with atrial tachyarrhythmias. However, only a few studies have appraised atrial tachyarrhythmias and atrial depolarization abnormalities in connection with high-grade IAA. We conducted a collaborative retrospective study to assess this association. METHODS: One hundred consecutive autopsied hearts were studied histologically for IAA. To increase the specificity for atrial depolarization abnormalities in this preliminary study, we excluded those specimens with intermediate amyloid involvement, i.e. IAA grades 1 and 2 (grade 0 = absent or trivial deposits; grade 1 = small deposits; grade 2 = moderate deposits; grade 3 = dense, large deposits). We then screened for baseline, premortem electrocardiograms (ECGs) to assess rhythm. In those with sinus rhythm, the P wave axis, duration, dispersion and terminal force in V1 were determined under magnification. RESULTS: Of the 27 premortem ECGs corresponding to the autopsy specimens with grades 3 (sample) or 0 (controls) IAA, 9 showed sinus rhythm, 13 showed atrial fibrillation, 1 showed atrial flutter and 4 were uninterpretable. Fourteen autopsied hearts (52%) were positive for grade 3 IAA. Ten of those had atrial tachyarrhythmias (9 atrial fibrillation and 1 atrial flutter) compared to 4 of the 13 hearts with grade 0 IAA (72 vs. 31%, respectively; p = 0.03). Although there was excellent interobserver agreement using intraclass correlation coefficients, there were no significant differences in P wave measurements among the small number of patients with sinus rhythm for grade 3 versus grade 0 IAA. CONCLUSION: In a collaborative, preliminary, pilot assessment of autopsied hearts for which premortem ECGs were necessarily screened retrospectively, significantly more hearts with high-grade IAA were associated with atrial tachyarrhythmias compared to those with low-grade IAA. A larger study with an appropriately matched autopsy control group is needed to confirm these and previous observations.

Interatrial block: the pandemic remains poorly perceived.

Interatrial block (IAB; P duration >or=110 ms) is a common electrocardiogram abnormality, which in addition to reduced left atrial function predicts atrial fibrillation and other arrhythmias. P terminal force (Ptf) +/- biphasic P in lead V(1)>or= the area of one small square on the grid also indicates left atrial abnormality, particularly left atrial enlargement, which is a strong correlate of IAB. Among 482 consecutively recorded electrocardiograms, IAB and Ptf were strongly and significantly correlated (chi(2)= 68.041; P

Is there a role for statins in atrial fibrillation?

3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are some of the most commonly prescribed drugs in the world. While lipid modification remains the primary function of statins, there has been increasing interest in its potential pleiotropic effects, particularly as an anti-inflammatory agent in its role as an antiarrhythmic. Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and carries with it a significant burden in both morbidity and mortality. Treatment for AF currently involves either rate or rhythm control where both have demonstrable associated risks. Rate control necessitates anticoagulation, which can cause life-threatening bleeding, while rhythm control has a poor side-effect profile that may lead to greater mortality and may not completely eliminate the need for anticoagulation. Considering this pressing need for novel therapeutic interventions in AF, this long overdue systematic review explores the potential role of statins in the treatment and prevention of AF. Physicians, especially cardiologists, need to be aware of the host of currently available literature and, more importantly, need to be stimulated to generate discussion and formulate studies that will help debate the issues under the most erudite standards.

Interatrial block: correlation with P-terminal force.

BACKGROUND AND HYPOTHESIS: Interatrial block (IAB: P-duration > 100 ms) is poorly recognized in hospital populations. In addition to reduced left atrial function and left atrial enlargement it predicts atrial fibrillation and other arrthymias. P-terminal force (Ptf): +/- biphasic P in lead V(1) > or = area of 1 small square on the electrocardiogram (ECG) grid also indicates left atrial abnormality, particularly left atrial enlargement. These 2 should be related. We determined the intercorrelation. METHODS AND RESULTS: Two blinded observers evaluated 500 consecutive patients' ECGs for both Ptf and IAB utilizing all 12 leads for IAB and V(1) for Ptf. Measurement differences were resolved in a consensus conference. Among 482 usable ECGs, IAB and Ptf were strongly and significantly correlated (chi(2) = 68.041; P < or = .001). CONCLUSION: IAB and Ptf are significantly and strongly correlated and one should be expected in the majority of cases when the other is recognized.

Is the presence of mitral annular calcification associated with poor left atrial function?

INTRODUCTION: Mitral annular calcification (MAC) is characterized by calcium and lipid deposition in the annular fibrosa of the mitral valve. MAC is associated with cardiovascular events but little is known of its association with left atrial (LA) function. METHODS: We prospectively obtained 12-lead electrocardiograms (ECGs) and transthoracic echocardiograms (TTE) on patients scheduled for nonemergent echocardiographic assessment at a tertiary care hospital. MAC was graded as 0 = none, 1 = mild, 2 = moderate, 3 = severe. LA linear and volume measurements (stroke volume, LA passive emptying fraction, LA active emptying fraction and LA kinetic energy) were done specifically in addition to commonly measured TTE parameters. RESULTS: From the 124 considered for the study, 72 patients remained (aged 68+/-18 years; 44% male) after excluding those with poor ECG tracings and/or poor TTE images. Eighteen patients had MAC; mild MAC = 14, moderate MAC = 3, severe MAC = 1. When patients with MAC were compared to those without MAC, no significant difference was noted, except for LA linear dimension index (2.1+/-0.4 vs. 1.9+/-0.3 cm/m(2); P = 0.03). For those with mild and moderate MAC, a trend was noted toward lower LA function with increasing MAC severity. In addition, significant differences were noted between those with and without interatrial conduction delay, where those with such delay had significantly impaired LA stroke volume (9.8+/-3 vs. 19.93+/-4 ml; P < 0.0001), LA active emptying fraction (18.83+/-8 vs. 65.71+/-9%; P < 0.0001) and LA total/reservoir fraction (39.54+/-6 vs. 75.1+/-6%; P < 0.0001). CONCLUSIONS: MAC is associated with increase in LA linear dimension on TTE and may be equally represented with lower overall LA function. Further study in a much larger cohort is warranted to delineate these and other potential associations of MAC.

Formulaic quantification of echocardiographic left atrial volume.

INTRODUCTION: The association between increasing severity in abnormal atrial depolarization and left atrial (LA) volume derived by transthoracic echocardiogram (TTE) has been described through the following regression formula: LA end-systolic volume index (LAVI [milliliter]) = 8.0 + 0.2 (P-wave duration [millisecond]) (r = 0.47; P = .0002). However, prospective assessment of this formula has not been validated among inpatients outside the institution where it was first derived. METHODS: We prospectively obtained 12-lead electrocardiograms (ECGs) and TTEs on consecutive inpatients who were scheduled for nonemergent echocardiographic assessment. P waves were assessed independently to the nearest 10 milliseconds for application of the formula with a Bland-Altman plot. P-wave durations were obtained specifically from lead II and also from the any lead that yielded the widest measurement. RESULTS: After excluding those with poor ECG tracing and TTE images, 72 patients were studied. We found a strong formulaic correlation with LAVI by TTE when maximal P-wave measurements were obtained from any ECG lead (r = 0.67; P < .0001) and more so, when restricted only to lead II (r = 0.89; P < .0001). Correlation was strongest when there was no or minimal difference between P-wave measurements in lead II and all other leads (r = 0.84; P < .0001 for no difference vs r = 0.67; P < .0001 for 60-millisecond difference). The Bland-Altman plot showed good agreement of LAVI assessment using the formulaic estimation when compared to TTE measurements derived by Simpson's rule (coefficient of reproducibility for 2 SD equivalent to 8.8% for lead II and 11.4% for any lead). CONCLUSION: There is good agreement and correlation between formulaic estimation and that of TTE for LAVI among inpatients. Such quantification of LA size not only serves as an indirect asset that could perhaps supplement TTE measurements in certain circumstances but also can facilitate risk stratification of patients.

Relation of recurrence of atrial fibrillation after non-ST-elevation acute myocardial infarction to left atrial abnormality.

Atrial fibrillation (AF) is common during the course of acute myocardial infarction and is associated with left atrial (LA) dilatation. However, the role of LA depolarization abnormality on the electrocardiogram (ECG) in the setting of LA dilatation was not studied in this context. Patients admitted with non-ST-segment elevation myocardial infarction (NSTEMI) who developed new-onset AF (International Classification of Diseases, Ninth Revision code 427.31) were prospectively identified. Baseline ECGs and echocardiograms before the admission event were reviewed. Follow-up was directed toward pertinent cardiovascular events, atrial tachyarrhythmias, and death as end points. Of 101 patients with NSTEMI who had new-onset AF, 88 had current echocardiograms and 69 had LA dilatation (78%). Total follow-up was 24 months (mean 21.4). Prolonged P-wave duration (> or =110 ms) and decreased left ventricular fractional shortening were most significant in those with LA dilatation and were independently associated with AF. In those with LA dilatation, the prevalence of such abnormal atrial depolarization on ECGs was 56%. AF (43% vs 15%; p = 0.03) and heart failure (63% vs 35%; p = 0.03) occurred more often in this subset, but there was no difference in mortality. However, the overall prevalence of late cardiovascular complications in this subset was higher (71% vs 45%; p = 0.02) compared with that of immediate complications (20% vs 26%; p = 0.60). In conclusion, there is higher recurrence of AF in patients with NSTEMI who have a combination of electrocardiographic and echocardiographic LA abnormalities compared with those without.

Risk stratification for recurrent heart failure in patients post-myocardial infarction with electrocardiographic and echocardiographic left atrial abnormality.

Left atrial enlargement is predictive of cardiovascular events. The predictive power, however, of the combination of electrocardiographic (LAE-ECG) and echocardiographic left atrial enlargement (LAE-Echo) has not been extensively evaluated. We prospectively identified patients admitted with non-ST-segment elevation myocardial infarction (NSTEMI) who developed new-onset heart failure during admission. Baseline electrocardiograms obtained < or =12 months before admission were evaluated for LAE-ECG, such as prolonged P-wave duration or positive P-wave terminal force in lead V1, and in-hospital echocardiographic reports obtained < or =1 month after admission were assessed for linear, anteroposterior LAE-Echo. Follow-up was directed toward pertinent cardiovascular events and death. Of the 462 patients with NSTEMI, 108 developed new-onset heart failure (23%); 71 patients had LAE-Echo. Follow-up was 23.2 months (mean 22.1 months). Although in-hospital (early) cardiovascular complications (other than heart failure) were not significantly higher in patients with LAE-Echo, these patients demonstrated more postdischarge (late) cardiovascular complications, predominantly recurrent heart failure. In addition, those with a combination of LAE-Echo and LAE-ECG demonstrated significantly higher recurrence of heart failure (hazard ratio 1.52, 95% confidence interval 1.12 to 4.35; p = 0.02 for interatrial conduction delay, and hazard ratio 1.07, 95% confidence interval 1.01 to 3.27 for P-wave terminal force in lead V1; p = 0.03) and increased mortality compared with those with LAE-Echo alone. In conclusion, our data suggest that a combination of electrical and mechanical left atrial dysfunction is significantly more predictive of increased cardiovascular events and mortality compared with left atrial mechanical dysfunction alone.

Differences in treadmill exercise tolerance parameters between patients with partial and advanced interatrial depolarization abnormality.

Advanced interatrial block (aIAB) is considerably much less common than partial interatrial block (pIAB), occuring in <2% of the elderly hospitalized population. Less is, therefore, known of the true clinical burden of aIAB, particularly in relation to graded exercise. Therefore, 12 patients with aIAB and 30 patients with pIAB who performed a baseline exercise tolerance test and had a repeat test performed > or = 2 years later were included in the study. Exercise tolerance, echocardiographic findings, and major adverse cardiovascular events were compared. Left atrial size progressed at a significantly faster rate in those with aIAB. In addition, Duke Prognostic Treadmill scores were significantly lower on follow-up in those patients with aIAB. Overall, patients with aIAB had significantly greater left atrial size (48.3 +/- 9 vs 42.8 +/- 4 mm, p < 0.01) and significantly lower Duke Prognostic Treadmill scores than those with pIAB (-0.2 +/- 5 vs 4.1 +/- 4, p < 0.05). There were, however, no significant differences in the occurence of major adverse cardiovascular events. In conclusion, left atrial size progressed at a significantly faster rate but Duke Prognostic Treadmill scores were significantly lower in those with aIAB compared with patients with pIAB after > or = 2 years of follow-up. Further study is required to determine whether patients with aIAB require follow-up echocardiography and/or exercise tolerance tests for optimal risk stratification.

Late gadolinium enhancement cardiovascular magnetic resonance in genotyped hypertrophic cardiomyopathy with normal phenotype.

A 35 year-old asymptomatic Caucasian female with a family history of hypertrophic cardiomyopathy (HCM) was referred for cardiologic evaluation. The electrocardiogram and transthoracic echocardiogram were normal. Cardiovascular magnetic resonance (CMR) was performed for further assessment of myocardial function and presence of myocardial scar. CMR showed normal left ventricular systolic size, measurements and function. However, there was extensive, diffuse late gadolinium enhancement (LGE) throughout the left ventricle. This finding was consistent with extensive myocardial scarring and was highly suggestive of advanced, non-ischemic cardiomyopathy. Genotyping showed a heterozygous mis-sense mutation (275G>A) in the cardiac troponin T (TNNT2) gene, which is causally associated with HCM. There have been no previous reports of such extensive, atypical pattern of myocardial scarring despite an otherwise structurally and functionally normal left ventricle in an asymptomatic individual with HCM. This finding has important implications for phenotype screening in HCM.

Exercise-induced improvement in atrial depolarization abnormality in a patient after treatment with beta-adrenergic blockers.

Abnormal atrial depolarization, characterized by P waves >or=110 ms on the electrocardiogram, can manifest as partial or advanced interatrial conduction delay or interatrial block (IAB). Progression from partial to advanced IAB has been shown to be altered by the use of angiotensin-converting enzyme inhibitors and beta-adrenergic blockers. We previously reported that advanced IAB, denoted by biphasic P waves in leads II, II and aVF, can revert intermittently to its partial counterpart. However, potential factors that could induce such resolution remain unknown. We present the first known case of resolution of advanced IAB to partial IAB occurring during graded exercise, following treatment with a beta-adrenergic blocker. Only continued study of these and other novel factors will help us understand the exact pathophysiology of both, partial and advanced IAB.

Induction of atrial depolarization abnormality during dipyridamole stress imaging: a cautionary note.

P-wave widening on the 12-lead electrocardiogram denotes abnormal atrial depolarization and has been shown to be associated with myocardial ischemia during treadmill exercise tolerance testing. However, its true significance during dipyridamole (Persantine) stress imaging remains questionable given the potential direct as well as indirect effects of dipyridamole on the atria. We present a novel series of 5 comparable cases of dipyridamole stress imaging where serial P-wave duration increase occurred during administration of dipyridamole. We observed that such P-wave widening occurred even in the absence of evidence of myocardial ischemia on subsequent myocardial perfusion imaging. Clinicians should therefore be aware of this potential association where, unlike that observed with graded exercise treadmill testing, P-wave widening during dipyridamole infusion could perhaps be a pharmacological effect on the atria instead of an indication of underlying myocardial ischemia.

Intermittent advanced atrial depolarization abnormality?

Abnormal atrial depolarization, characterized by P waves > or =110 ms on the electrocardiogram, can manifest as partial or advanced interatrial block (IAB). Advanced IAB, denoted by biphasic P waves in leads II, II and aVF, is considered to confer increased severity in interatrial conduction delay, and is now perceived to be a result of continued deterioration in interatrial impulse propagation between the atria. While progression from partial to advanced IAB has been described, the converse, resolution of advanced IAB, which has often been touted as 'complete block' to its partial, 'incomplete' type, i.e. the occurrence of intermittent advanced IAB, has escaped observations so far. We present the first known report of such a scenario.

Can U waves be "notched"?

Abnormal U waves (unduly larger or misshapen) are associated with several conditions such as hypokalemia, arrhythmias, cardiac ischemia, ventricular hypertrophy, and hypertension. Abnormal U waves have also been linked to certain cardiac medications, predominantly antiarrhythmics. However, mechanisms of U-wave-abnormality remains debated and perhaps elusive with the true U-wave relationship to T waves still being investigated. While there have indeed been reports of bifid ("notched") T waves, such comparably described U waves have escaped us thus far. We present a case of possibly bifid U waves that persisted over the course of 10 years in the setting of repeated negative Holter monitor findings and clinical absence of atrial tachyarrhythmias. We take this opportunity to briefly discuss common causes of "normal" and abnormal U waves.

Giant right atrium in an adult.

Massive right atrial (RA) enlargement is certainly more common in children than in adults, owing to rare congenital anomalies. Indeed, the largest description of such chamber enlargement was noted in a child, where the RA volume was reported to be 900 ml. We now report one of the largest descriptions of the RA in an adult, in absence of tricuspid stenosis and other common adult associations of RA abnormality, such as chronic pulmonary disease, severe mitral valvular pathology with pulmonary hypertension, and pulmonary embolism or infarct. The RA volume was estimated to be well over 500 ml and was notably disproportionate to that of the left atrium and either ventricle.

Chiari network endocarditis: not just an innocent bystander.

A Chiari's network, noted in approximately 2% of the general population, is a congenital remnant of the sinus venosum valve present in the right atrium. We report a case of a 67-year-old male who presented with acute infective endocarditis of the tricuspid valve due to coagulase-negative Staphylococci. Despite appropriate antimicrobial therapy for 2 weeks, the patient remained febrile with septic emboli to the pulmonary vasculature. Repeat transthoracic echocardiography (TTE) revealed persistent vegetations adherent to the tricuspid valve, extending onto the Chiari network, necessitating surgical intervention.

Spontaneous alternans in Brugada ST-segment morphology within minutes.

Brugada syndrome is an inherited, life-threatening, cardiac channelopathy where the electrocardiogram (ECG) characteristically depicts a classic pattern of complete or incomplete right bundle-branch block with ST-segment elevation in the right precordial leads V(1) to V(3). These, almost inalienable, ECG patterns may be dynamic, where changes may resolve to baseline or one particular type may evolve into another. Such alternans has been described with fever, electrolyte imbalances, atrial pacing, glucose and/or insulin administration, psychotropic drugs, beta-adrenergic blocker use, class IA and IC antiarrhythmic provocation testing, such as with ajmaline, procainamide, or flecainide, and even large meals, that is, "full stomach sign." However, spontaneous alternans between the different types of Brugada ECG patterns (types) have not been reported within minutes, in the absence of previously described precipitating factors. We present a novel case where classic, type 2, Brugada-like ECG pattern evolved spontaneously to type 1 before returning to type 2 within minutes of presentation.

High prevalence of widened P waves among pediatric patients in 2 separate hospitals.

INTRODUCTION: In adults, P waves of 110 milliseconds or longer are often associated with significant disease. In the pediatric population, however, cutoffs for P-wave durations are naturally lower but could vary physiologically with age because of increasing heart mass. We appraised if age-proportionate increase in P-wave duration does indeed occur in both hospitalized infants and children and also investigated the prevalence of widened P-wave durations using currently accepted "normal" cutoffs (

Angiographic localization of potential culprit coronary arteries in patients with interatrial block following a positive exercise tolerance test.

Interatrial block (IAB), denoted by P waves > or =110 ms, is believed to be associated with underlying ischemia, particularly with that of its principal interatrial conduction pathway, the Bachmann bundle. We investigated if there is an angiographic association of IAB on electrocardiograms at rest in patients who underwent cardiac angiography after a positive exercise tolerance test (ETT) result. Twenty-seven patients with IAB and 42 control patients without IAB on electrocardiograms at rest who had evidence of ischemia on cardiac angiography after ETT were identified. Coronary vessels that were angiographically most significantly stenosed (> or =70% occlusion indicating stenosis) were noted for statistical comparison (a p value <0.05 was considered statistically significant). Among patients with IAB, the right coronary artery was the predominant vessel to be affected, with > or =70% narrowing compared with the left, inclusive of the left main, left circumflex, obtuse marginal, and diagonal coronary arteries (58% vs 23%, p = 0.03). Right coronary artery lesions in patients with IAB were mostly in the proximal and mid portions (54% vs 25% for the entire left coronary artery, p = 0.02). No such difference was noted in control subjects. In conclusion, in patients with IAB at rest who have coronary heart disease, the right coronary artery is predominantly more significantly affected.