Diagnostic issues in the clinical management of pericarditis.

AIMS: To review the current major diagnostic issues on the diagnosis of acute and recurrent pericarditis. METHODS: To review the current available evidence, we performed a through search of several evidence-based sources of information, including Cochrane Database of Systematic Reviews, Clinical Evidence, Evidence-based guidelines from National Guidelines Clearinghouse and a comprehensive Medline search with the MeSH terms 'pericarditis', 'etiology' and 'diagnosis'. RESULTS: The diagnosis of pericarditis is based on clinical criteria including symptoms, presence of specific physical findings (rubs), electrocardiographical changes and pericardial effusion. Although the aetiology may be varied, most cases are idiopathic or viral, even after an extensive diagnostic evaluation. In such cases, the course is often benign following anti-inflammatory treatment, and management would be not affected by a more precise diagnostic evaluation. A triage of pericarditis can be safely performed on the basis of the clinical and echocardiographical presentation. Specific diagnostic tests are not warranted if no specific aetiologies are suspected on the basis of the epidemiological background, history and presentation. High-risk features associated with specific aetiologies or complications include: fever > 38 degrees C, subacute onset, large pericardial effusion, cardiac tamponade, lack of response to aspirin or a NSAID. CONCLUSIONS: A targeted diagnostic evaluation is warranted in acute and recurrent pericarditis, with a specific aetiological search to rule out tuberculous, purulent or neoplastic pericarditis, as well as pericarditis related to a systemic disease, in selected patients according to the epidemiological background, presentation and clinical suspicion.

Therapy for recurrent acute pericarditis: a rheumatological solution?

OBJECTIVE: To assess the efficacy of a multidrug protocol in recurrent acute pericarditis. We tried also to assess the specific role of colchicine. METHODS: We studied 58 patients (34 males) in the largest monocentric observational study. All patients received prolonged courses of non-steroidal anti-inflammatory drugs; generally we do not start a corticosteroid in recurrent acute pericarditis, but if a steroid had already been started, we planned a very slow tapering; if necessary azathioprine, hydroxychloroquine, and other immunosuppressive drugs were used; 44 patients (27 males, 61.4%) were treated also with colchicine and 14 patients (7 males, 50%) were not given this drug. RESULTS: After starting our protocol recurrences dropped from 0.48 to 0.03 attacks/patient/month (p < 0.00001) within 12 months and remained at the same level till the end of the follow-up (mean 8.1 years) in the whole cohort. In the 44 patients treated with colchicine recurrences dropped from 0.54 to 0.03 attacks/patient/month (p < 0.00001) within 12 months, and in 14 patients not given colchicine recurrences decreased from 0.31 to 0.06 attacks/patient/month (p = 0.002). In patients treated with colchicine the decrease was significantly higher (0.51) than in patients not taking this drug (0.25) (p = 0.006). Colchicine was discontinued by 16.3% of patients because of side effects. CONCLUSION: A multidrug protocol including non-steroidal anti-inflammatory drugs at high dosage, slow tapering of corticosteroid, colchicine, reassurance and close clinical monitoring is very effective in recurrent pericarditis; this improvement is more dramatic in colchicine treated patients, but also patients who do not tolerate it can achieve good control of the disease.

Global T wave inversion.

Because global T wave inversion has not been specifically characterized, 100 electrocardiograms (ECGs) with this pattern (frontal plane T vector -100 degrees to -170 degrees with precordial T inversion) were prospectively collected from approximately 30,000 consecutively interpreted ECGs and analyzed blindly. There was a striking female predominance (82 women vs. 18 men; p less than 0.0005) despite an essentially equal number of female and male hospital admissions. There was a single statistically significant ECG correlate: a more vertical QRS axis in women (+14.1 degrees +/- 45.3 degrees vs. -5.6 degrees +/- 31.3 degrees; p = 0.034). The T waves were basically symmetric (68%), the influence of this factor usually altering the characteristically asymmetric T wave inversions of right bundle branch block (4 of 5) and left ventricular hypertrophy (21 of 36). Asymmetry was mainly associated with digoxin therapy (21 of 32 patients taking digoxin; p less than or equal to 0.0005) and a corrected QT (QTc) interval (0.433 +/- 0.095) shorter than with symmetric T wave inversions (0.507 +/- 0.074; p less than or equal to 0.0005) though not reaching the degree of shortening expected for digitalization. Twenty-eight patients admitted for acute myocardial infarction and 23 for a central nervous system disorder accounted for the majority of patients with symmetric T wave inversion. Fifteen of 18 patients who had coronary angiography had some degree of coronary artery disease: 3 had angiographically normal coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Global T wave inversion: long-term follow-up.

OBJECTIVES: This study evaluated 11-year follow-up data from patients with global T wave inversion. BACKGROUND: In an 8-year prospective investigation, global T wave inversion was characterized by a long QT interval, unexplained marked female preponderance and, despite dramatic electrocardiographic (ECG) changes, an in-hospital prognosis not statistically different from that of the entire hospital population in which the condition it occurred. METHODS: To assess long-term prognosis, these and an additional 18 patients (total 118 patients; 92 women and 26 men) with global T wave inversion were followed up prospectively for up to 11 years (mean 33.9 +/- 37.3 months). The additional patients did not significantly affect the in-hospital death rate (7.6%; previously reported death rate 8%) and the total series continued not to differ from the entire in-hospital population in which it occurred (7.02%; p = NS). RESULTS: Long-term survival was shortened by digoxin, faster heart rates, atrial fibrillation and, especially, a malignant condition. Eighteen (78.3%) of 23 patients with a malignant condition died during the follow-up period (p < or = 0.0005), with a mean survival time of only 12 months. Kaplan-Meier curves also revealed the poor prognosis for those patients taking digoxin; 21 (63.9%) of 36 patients died (p = 0.008). Eleven of the 12 patients with atrial fibrillation were taking digoxin; 58.3% of these died, demonstrating a worse prognosis than that of patients with sinus rhythm, 35% of whom died (p = 0.005). CONCLUSIONS: Global T wave inversion continues to have an unexplained (78% vs. 22%) female preponderance. Although the long-term prognosis depends on underlying or associated diseases, the striking diffuse ECG changes do not in themselves imply a poor prognosis.

Q-wave versus non-Q wave myocardial infarction: a meaningless distinction.

The whole subject can thus be summed up in two statements. 1. Every appropriately designed study comparing first Q and NQMI's has found no difference in post-MI course of the two categories and no foundation for the common notion that the NQMI is a uniquely "unstable" entity, to be classed with unstable angina in terms of prognosis and management. Nine such studies have been published. On the other hand, all studies alleging the "unstable" character of the NQMI have been invalidated by major flaws, chief among them the comparison of undifferentiated mixtures of first and subsequent infarcts with widely differing mortality and morbidity. This confusion is further compounded by the fact that subsequent infarcts generate Qwaves less than half as often as first infarcts. 2. All current studies indicate that there is no benefit to an invasive as compared with a conservative protocol for management of NQMI. Since the characterization of an infarct as "non-Q' conveys no therapeutic implications, the classification becomes irrelevant and should be discarded. Two quotations sum the whole matter succinctly. Moss (63) commented that "The Q-wave versus non-Q-wave categorization does not provide sufficient sensitivity, specificity, or predictive accuracy about the subsequent clinical course of patients with a first myocardial infarction to use it as reliable data in the clinical decision-making process." Surawicz (64) put the matter even more concisely: ". . . a non-Qwave MI is not a unique entity: rather it is a smaller and less extensive MI." In a word, the magnitude of a myocardial infarction should be judged on anatomical and functional considerations rather than on the designation of Qwave versus non-Qwave infarction.

Cardiomyopathy of limb-girdle muscular dystrophy.

OBJECTIVES: This study sought to find an association between dilated cardiomyopathy and limb-girdle muscular dystrophy. BACKGROUND: Cardiomyopathy has been seen in various neuromuscular disorders, but it has not been recognized to be associated with limb-girdle muscular dystrophy. METHODS: We investigated three sisters with well documented limb-girdle dystrophy and congestive heart failure by the 3rd decade of life. All underwent noninvasive evaluation of left ventricular systolic function by both echocardiography and radionuclide scanning, and one also had cardiac catheterization. Deoxyribonucleic acid (DNA) linkage analysis was performed in these affected subjects and in the unaffected family members, and DNA was extracted from mononuclear cells with primer sequences for three chromosome 13q microsatellite markers. RESULTS: The parents had no evidence of clinical disease, but all three sisters had echocardiographic evidence of dilated cardiomyopathy. The sister with additional evidence of left ventricular dysfunction of cardiac catheterization had no coronary artery disease. The affected subjects had the same paternal allele for three potential markers of limb-girdle muscular dystrophy but different maternal alleles. The very small family size did not permit statistical confirmation or refutation of linkage for chromosome 13q markers. CONCLUSIONS: Demonstrable cardiomyopathy accompanying limb-girdle muscular dystrophy and its probable genetic associations require continued investigation by anticipating the cardiomyopathy in limb-girdle muscular dystrophy.

Effective management of congestive cardiomyopathy. Relation to ventricular structure and function.

Until recently, congestive cardiomyopathy has had a poor prognosis on standard treatment because of severe congestive failure, arrhythmias, and embolism from endocardial thrombi in both ventricles. This pluricausal disorder differs from other heart disease because of disproportionately small hypertrophy in relation to ventricular dilation, with ultimate severe impairment of systolic function. Absence of hypertrophy adequate to compensate dilation exaggerates ventricular wall stress beyond that seen in other disorders. Newer treatments seeming to promise unprecedented improvement include unloading therapy with vasodilators, nonglycoside inotropic therapy, beta-adrenoceptor blockade (experimental only), combinations of these agents with or without digitalis and diuretics, and intra-aortic balloon pumping for critical failure. New surgical approaches include mitral annuloplasty, coronary bypass (for ischemic cardiomyopathy), and, for appropriate recipients, cardiac transplantation.

The randomized controlled clinical trial. Scientific and ethical bases.

Randomized controlled trials are increasingly accepted in principle but not always in practice, particularly for surgical therapies. Successful surgical randomized controlled trials demonstrate their feasibility, and reports of uncontrolled surgical trials now commonly bear a statement that a definitive answer requires a controlled trial. Scientifically, the randomized controlled trial is the most powerful way to determine a result ascribable only to the trial treatment. Although randomized controlled trials can be imperfect or improperly conducted, they are designed to circumvent biased behavior by investigators. With candor in informed consent, the equal chance not to get a trial treatment makes the randomized controlled trial the most ethical design. Thus, scientific, behavioral, and ethical cases support the randomized controlled trial as the optimal method for investigation of nearly all therapeutic innovations and as a requirement for publication.

Infection and infarction. Acute viral (and other) infection in the onset, pathogenesis, and mimicry of acute myocardial infarction.

Because a prospective controlled investigation showed a highly significant association of the onset of acute myocardial infarction with signs of preceding respiratory infection, the clinical, laboratory, experimental, and epidemiologic evidence more directly supporting this association was analyzed. Inflammation--specifically of infectious, usually viral, origin--has been shown by several lines of evidence to be capable of precipitating or mimicking clinical myocardial infarction. Myocardial biopsy is producing rapidly increasing confirmation that myocarditis can perfectly mimic clinical acute myocardial infarction. Coronary arteritis, with implications for vasospasm and thrombosis, is being increasingly demonstrated when deliberately sought in necropsy and biopsy material. Effects of blood-borne infectious agents, particularly viremia, on platelets in vivo and in vitro--aggregation and lysis with release of vasoactive substances--have even more serious potential for coronary thrombosis and vasospasm. It is not clear whether such mechanisms operate entirely independently or are more potent in high-risk patients, particularly in view of the demonstrable hypercoagulable state in many patients with coronary disease. Because of the great importance of confirming precipitating mechanisms for acute myocardial infarction (as well as its frequent mimic, myocarditis), intensive investigation of the relation between infection and infarction has important preventive and therapeutic implications.

Electromechanical dysfunction of the left atrium associated with interatrial block.

OBJECTIVES: Our purpose was to determine the effect of interatrial block (IAB, P-wave duration >/=120 ms) on left atrial (LA) dynamics. IAB is associated with LA enlargement (LAE). LA dysfunction is associated with decreased left ventricular filling, a propensity for LA appendage thrombus formation, and reduced atrial natriuretic peptide levels. We evaluated LA function in patients with and without IAB matched for LA size. METHODS: Echocardiograms with LA enlargement were analyzed. Twenty-four patients had IAB, and 16 patients without IAB formed the control group. LA volumes, A-wave acceleration times (At), LA stroke volume (LASV), ejection fraction (LAEF), and kinetic energy (LAKE) were calculated. RESULTS: The control group and patients with IAB had comparable maximal LA volume and diameter (P >.05). Patients with IAB had significantly longer At (115 +/- 39 ms vs 83 +/- 24 ms, P <.01) and smaller LASV (7 +/- 5 mL vs 17 +/- 6 mL, P <.01), LAEF (9% +/- 6% vs 25% +/- 8%, P <.01), and LAKE (20 +/- 14 vs 65 +/- 44 Kdyne/cm/s, P <.01). LAKE varied inversely with P-wave duration (r = -0.51, P <.01). P-wave duration and minimal LA volume were independent determinants of LAEF. CONCLUSIONS: Patients with IAB have a sluggish, poorly contractile LA, and the extent of dysfunction is related to the degree of electrical delay from IAB. IAB should be considered a marker of an electromechanically dysfunctional LA and hence a risk factor for atrial fibrillation and congestive heart failure.

Frequency of arrhythmias in acute pericarditis determined by Holter monitoring.

Twenty-four-hour electrocardiographic monitoring in 49 of 50 consecutive patients with acute pericarditis and sinus rhythm at onset (29 with etiologic or unrelated heart disease) disclosed 4 instances of intermittent supraventricular tachycardia, 2 in patients in whom tamponade developed and 1 in a patient with acute myocardial infarction. Eight other arrhythmias, also nonsustained. occurred exclusively in patients with heart disease. Ectopic beats without other arrhythmia occurred in 10 patients without heart disease, but were infrequent (1 to 30 per hour) in 9. Ectopic beats without other arrhythmias occurred in 19 patients with heart disease but were infrequent in 16. Pericarditis per se does not appear to be a recognizable arrhythmogenic influence. As a corollary, significant rhythm disturbance--particularly continuous-beat arrhythmias--during acute pericarditis implies a cardiac abnormality.

Absent septal q wave: the neglected deflection.

Absence of the normal septal q wave in leads I and V6 is often overlooked. It correlates with a range of pathologic changes, including septal scarring and incomplete left bundle branch block.

Pericardial rub. Prospective, Multiple observer investigation of pericardial friction in 100 patients.

A prospective, multiple observer ausculatory and phonocardiographic study of 100 patients with pericardial friction confirmed the dominant prevalence of triphasic pericardial rubs (56 percent of patients with sinus rhythm). In 9 of 33 patients with various biphasic rub patterns there was summation of the ventricular diastolic rub with the atrial systolic rub, concealing an additional 10 percent of potential triphasic friction. Fourteen of 15 monophasic rubs were audible or recordable only during ventricular systole. Rubs were best heard along the left sternal border in 84 percent of cases and tended to be louder during inspiration than during expiration; in 35 cases there was no respiratory predilection. Twenty-three rubs were palpable. Ten rubs occurred in patients with pericardial effusion, five of whom had tamponade. Extension of the neck did not have a dependable effect on rub intensity.

Computer treason: intraobserver variability of an electrocardiographic computer system.

An electrocardiogram computer system significantly disagreed with itself in 36 of 92 pairs of unselected electrocardiograms which had not changed when recorded 1 minute apart.

Electromechanical delay in the left atrium as a consequence of interatrial block.

Right and left atrial electromechanical intervals and onsets of active right and left ventricular filling were measured in patients with interatrial block and compared with control patients. Left atrial mechanical activity is significantly delayed by interatrial block.

PR-segment deviation as the initial electrocardiographic response in acute pericarditis.

PR-segment deviations precede classic ST(J) deviations in acute pericarditis because the superficial myocarditis producing electrocardiographic changes is more encompassing in the thin atrial muscle. In patients with appropriate syndromes, PR-segment deviations should be recognized early after onset, as ST changes may be absent.

Respiratory effects on systolic time intervals during pericardial effusion.

Pericardial effusion without cardiac tamponade is defined by the detection of excessive pericardial fluid without clinical manifestations, particularly pulsus paradoxus (inspiratory decrease in systolic blood pressure greater than 10 mm Hg) and jugular venous distention. Nineteen consecutive patients without heart or lung disease who had pericardial findings and no evidence of tamponade were investigated by echocardiography: 14 with pericardial effusion and 5 with noneffusive ("dry") pericarditis. Patients with effusion had an inspiratory decrease in left ventricular ejection time (delta LVET) of 17.9 +/- 5.78 ms and an increase in preejection period (delta PEP) of 12.1 +/- 3.78 ms, each well beyond the respective respiratory changes measured in normal subjects. The 5 control patients with dry pericarditis had a mean delta LVET and delta PEP of only 8.0 and 7.0 ms, respectively. Of the 14 patients with effusion, 6 whose systolic pressure showed no respiratory change had mean delta LVET of 13.7 ms and delta PEP of 11.2 ms, comparable to the other 8 patients with effusion who had a respiratory change of 2 to 10 mm Hg. We conclude that although pulsus paradoxus was not present, excessive pericardial fluid is not physiologically inert. If a satisfactory echocardiogram is not available, exaggerated respiratory fluctuation in systolic time intervals may be evidence of excessive pericardial fluid.

Electrocardiographic correlates of absent septal q waves.

Compared with 100 consecutive electrocardiograms with septal q waves, 100 consecutive electrocardiograms without septal Q waves were otherwise normal only 4 times (vs 28 times; p <0.001). The strongest electrocardiographic correlate was QS in lead V1 (68 vs 4; p <0.001).

Auscultatory perception of the fourth heart sound: effects of interval form fourth to first sound (S4-S1) and aging.

A clinically heterogeneous group of 48 subjects (aged 19 to 76 years) were searched for a fourth heart sound (S4) by three independent "blind" auscultators. Phonocardiograms recorded immediately after auscultation were measured by another "blind" observer. An S4 was identified in 32 subjects (67 per cent) in phonocardiograms with nominal filter peaks of both 70 and 35 hertz. Results in these subjects revealed two groups by auscultatory performance: those with an "easily heard" and those with an "easily missed" S4. Subjects with an "easily missed" S4 were significantly younger than those with an "easily heard" S4 (31.2 +/- 2.8 years versus 50.0 +/- 4.0 years, P less than 0.001). P-R and P-S4 intervals and relative amplitude of S4 (ratio of fourth to first heart sound [S1] amplitude) were not significantly different in the two groups. Splitting of the first heart sound (S1) was observed more frequently in the phonocardiogram of patients with an "easily missed" S4, but this trend did not reach statistical significance. The interval between S4 and the low frequency component of S1 was significantly short in those with an "easily heard" S4 (49.4 +/- 4.1 msec versus 70.0 +/- 5.0 msec, P less than 0.005). The mean S4-S1 (low frequency component) interval for the group with an "easily heard" S4 approximated 1 cycle length for S4 vibrations, a finding consistent with temporal acoustic summation. An alternate hypothesis is modification of S1.