Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

Changes in QT dispersion during adenosine infusion.

BACKGROUND: QT dispersion (QTd) measurement during treadmill stress testing has been to shown to improve the accuracy of exercise electrocardiogram (ECG) in the detection of significant coronary artery disease (CAD). HYPOTHESIS: The aim of this study was to determine whether adenosine-induced changes in QTd could predict significant CAD and to assess its efficacy as a diagnostic index in patients undergoing adenosine stress test. METHODS: QT interval measurements were made in 57 consecutive patients undergoing adenosine sestamibi stress test. Patients with an abnormal stress test underwent coronary angiography. Patients with significant disease by coronary angiography (> 70% stenosis) were classified as having CAD (Group 1), and those with normal stress images and/or normal coronaries by angiography were classified as having no CAD (Group 2). RESULTS: QT dispersion increased from 28.2 +/- 4.5 to 43.8 +/- 4.5 ms with a delta QTd of 15.53 +/- 3.68 in Group 1 (p = 0.001) and from 28.4 +/- 2.6 to 34.8 +/- 2.8 ms with a delta QTd of 6.58 +/- 2.21 ms in Group 2 (p = 0.006). Patients in Group 1 had a significantly higher increase in QTd (delta QTd) than the patients in Group 2 (p < 0.03). Addition of delta QTd (> 10 ms) to the ST depression during adenosine infusion would increase the sensitivity of the ECG from 23 to 65% and decrease the specificity from 91 to 70% for diagnosis of significant CAD. CONCLUSIONS: delta QTd is significantly more prolonged in patients with CAD during adenosine infusion. It increases the sensitivity of the stress ECG in diagnosis of CAD during adenosine infusion when used as an adjuvant index.

Refractory vasospasm with a malignant course.

We present a patient with two rare disorders, recurrent vasospastic angina leading to cardiac transplant and acute aortic occlusion. The patient had recurrent episodes of coronary vasospasm presenting with unstable angina, acute myocardial infarction, and sudden cardiac death in spite of adequate therapy with nitrates and calcium-channel blockers. He went on to have a cardiac transplant. The patient later presented with acute aortic occlusion with concomitant renal and mesenteric artery spasm. The circumstances of the presentation raise the possibility of a generalized vasospastic predisposition that is responsible for both events. Smoking, the only known major risk factor other than atherosclerosis, was noted to be temporally related to both events in our patient.

Results of Stent Supported Percutaneous Transluminal Coronary Angioplasty in Octogenarians With Coronary Artery Disease.

Between January 1995 and July 1998, percutaneous transluminal coronary angioplasty was performed on 27 lesions in 24 octogenarians. Half of the patients were African American. Women comprised 67% of the study group. Patients with unstable angina and myocardial infarction constituted 54% of the cohort. Two-thirds of the patients (83%) had single vessel disease with predominant class A and B lesion complexity of the angioplasty site. Acute success rate was 92%. Stents were successfully placed in 11 subjects (46%). None had acute myocardial infarction, emergency coronary artery bypass surgery, or stroke as a complication of the procedure. One patient presenting with acute myocardial infarction complicated by cardiogenic shock, died. Significant bleeding complications requiring blood transfusions occurred in 17% of patients. Of the patients, 23 (96%) were discharged in a clinically stable condition. Follow up during a two year period was completed in 21 patients (88%). One patient died of cancer. Four subjects (19%) underwent repeat percutaneous transluminal coronary angioplasty. One other patient had recurrent chest pain requiring multiple hospitalizations. The remaining 16 patients (76%) remained free of recurrence of angina. We concluded that percutaneous transluminal coronary angioplasty with stent placement can be performed in octogenarians with a high rate of clinical and angiographic success with an acceptable range of morbidity and mortality, and favorable long term (two year) outcome. (c) 2000 by CVRR, Inc.

Short-term effect of coronary artery bypass grafting on the signal-averaged electrocardiogram.

Ventricular late potentials at the end of the QRS can be detected on the body surface during sinus rhythm by recording a signal-averaged electrocardiogram (SAECG). In patients with coronary artery disease, these late potentials have been shown to be markers for spontaneous or inducible ventricular tachycardia, or both. The short-term (before and 10 +/- 4 days after coronary revascularization) influence of coronary artery bypass grafting (CABG) on the quantitative SAECG variables was studied in 40 patients with chronic coronary artery disease. Twenty-five of these patients had a previous myocardial infarction. In the 15 patients without previous myocardial infarction, no abnormal SAECG indexes were recorded before CABG and no change in the quantitative SAECG variables was observed after surgery. In the patients with a previous myocardial infarction, 7 (28%) had a late potential before CABG. After CABG, 5 (71%) patients remained late potential-positive, whereas the other 2 (29%) lost their late potential. The mean values of their SAECG variables improved after coronary revascularization. In the entire group of postmyocardial infarction patients, the high-frequency QRS duration had shortened (p less than 0.01) after CABG (the other SAECG indexes did not change). The postoperative arrhythmic complications (transient atrial fibrillation, new onset of ventricular couplets) tended to be more frequent in the postmyocardial infarction group and in patients with late potentials. Our findings suggest that the reported increase in ventricular arrhythmias after CABG is probably not related to a change in the arrhythmogenic substrate for ventricular reentry but is associated with changes in the arrhythmogenic milieu.

Cardiac arrhythmias--update 1987.

Arrhythmias may result from abnormalities of impulse initiation (automaticity), conduction (slow conduction, block, reentry), or a combination. The central and peripheral nervous systems have an important influence on the genesis of cardiac arrhythmias. Sympathetic and parasympathetic fibers innervate both atria and ventricle. The study of clinical cardiac arrhythmias includes the use of invasive and noninvasive testing procedures. The ECG, ambulatory monitoring, esophageal recording, exercise testing, and signal averaging techniques are the currently used noninvasive tests. Intracardiac electrophysiologic studies and endocardial catheter mapping are invasive techniques. The treatment of cardiac arrhythmias includes the use of antiarrhythmic drugs, cardiac pacing (antibradycardia, antitachycardia), implantable automatic defibrillator, cardiac fulguration, and antitachycardiac surgery. Clinical cardiac arrhythmias are of two types, the bradyarrhythmias and the tachyarrhythmias. The tachyarrhythmia, in turn, may be supraventricular or ventricular. There are clinical syndromes specifically related to arrhythmias: preexcitation syndromes are associated with supraventricular tachyarrhythmias, long Q-T syndromes with ventricular tachyarrhythmias, and sick sinus syndrome with bradyarrhythmias. The "tachycardia-bradycardia syndrome" is a combination of atrial tachyarrhythmias and sinus node dysfunction (some of the patients may also have ventricular tachyarrhythmias). Specific arrhythmias are recognized by their ECG characteristics. These arrhythmias also have specific electrophysiologic features which can be defined during invasive electrophysiologic studies. Cardiac arrhythmias may or may not be accompanied by underlying organic heart disease. Their treatment is related to the specific diagnosis and mechanism of the rhythm disturbance. The presence and extent of underlying organic heart disease is an important factor in the selection of antiarrhythmic therapy (drug, pacemaker, or surgery).

The role of Holter monitoring in patients with recurrent sustained ventricular tachycardia: an electrophysiologic correlation.

The significance of spontaneous ventricular premature depolarization (VPD) frequency and severity in patients with sustained ventricular tachycardia undergoing serial electrophysiologic studies (EPS) are unknown. Nineteen patients with sustained ventricular tachycardia were studied with 24-hour Holter recordings prior to control EPS and prior to each drug trial. Successful drug or surgical treatment (with the exception of amiodarone) was based upon noninducibility of ventricular tachycardia in the laboratory. Among the eight noninducible and nonamiodarone medically treated patients, two (25%) had significant VPD reduction and/or Lown class improvement. The remaining six (75%) had no change or worsening of Holter findings, despite noninducibility of sustained VT. Among the six amiodarone-treated patients, five of whom were persistently inducible prior to discharge, four (66%) had improved and two (33%) had worsened Holter findings compared to control. None of the five (100%) surgically managed patients were inducible postoperatively, and three of the five (60%) had no change or worsening of Holter findings. We conclude that (1) EPS are superior to Holter findings in assessing successful management; and (2) Holter findings may be concordant or discordant during EPS serial drug trials or following surgery and therefore cannot predict the success or failure of the intervention.

Short PR interval and narrow QRS complex associated with pheochromocytoma: electrophysiologic observations.

A patient with a short (0.10 second) PR interval, narrow QRS complex and palpitation is described. Electrophysiologic studies demonstrated the presence of accelerated atrioventricular (AV) nodal conduction. Subsequently, a pheochromocytoma was found. Surgical removal of the tumor resulted in normalization of the PR interval. These findings suggest that the short PR interval and the accelerated AV nodal conduction were due to the effect of excess catecholamines on the AV conduction system.

Infiltrative cardiomyopathy with conduction disease and ventricular arrhythmia: electrophysiologic and pathologic correlations.

Two cases are described, one of cardiac sarcoidosis and another of primary cardiac amyloidosis, in which correlation was made between electrophysiologic and postmortem conduction system studies. In Case 1 the electrocardiogram revealed right bundle branch block with first degree and intermittent third degree atrioventricular (A-V) block and recurrent unifocal paroxysmal ventricular tachycardia. Electrophysiologic studies disclosed normal sinus rhythm with prolonged A-H (175 ms) and H-V (60 MS) intervals and extrastimulus induction of repetitive ventricular firing. Postmortem examination revealed a sarcoid aneurysm of the posterior left ventricle and granulomatous infiltration of the A-V node, His bundle and bundle branches. In case 2 the electrocardiogram revealed sinus bradycardia, a prolonged S-T interval and recurrent ventricular fibrillation. Electrophysiologic studies demonstrated a prolonged sinus nodal recovery time (6,080 ms) and H-V (85 ms) interval. Postmortem examination revealed marked amyloid infiltration of the sinoatrial node, atria, proximal bundle branches and left and right ventricular myocardium. There was thus excellent correlation between electrophysiologic and pathologic findings. These cases indicate the importance of making a clinical diagnosis of the disease that might in some cases allow specific therapeutic intervention in addition to antiarrhythmic therapy.

Self-initiated conversion of paroxysmal atrial flutter utilizing a radio-frequency pacemaker.

A patient is described with drug-resistant recurrent paroxysmal atrial flutter. Electrophysiologic studies demonstrated that flutter was inducible with rapid atrial stimulation (stimulation rates of 375 to 400/min) and convertible with rapid atrial stimulation (rates of 400 to 460/min). Because of the latter response, a radio-frequency atrial pacemaker was implanted, which allowed self-initiated conversion of flutter episodes with rapid stimulation.

Sites of conduction disease in aortic stenosis: significance of valve gradient and calcification.

Electrophysiologic studies were done in 32 patients with aortic stenosis. In 24 patients with intact A-V conduction, A-H intervals ranged from 55 to 145 msec and were prolonged in two. Two had split His bundle potentials. The H-V intervals ranged from 25 to 94 msec and were prolonged in 12. The mean H-V interval was 63 +/- 2.6 msec in 12 patients with calcific aortic stenosis compared with 50 +/- 4.9 msec in 12 without calcification (P less than 0.05). The mean H-V in 10 patients with aortic gradients greater than 40 mm Hg was 62 +/- 5.6 msec compared with 47 +/- 3.1 msec in nine with gradients less than 40 (P less than 0.05). In patients with aortic stenosis and A-V block, the site of the block was distal to the His bundle in three and within the His bundle in five. All eight had calcified valves. Aortic stenosis was commonly associated with latent and manifest conduction disease in the His bundle and the trifascicular conduction system. Conduction disease was more extensive with calcified valves and greater valve obstruction.

Intractable paroxysmal tachycardia caused by a concealed retrogradely conducting Kent bundle. Demonstration by epicardial mapping and cure of tachycardias by surgical interruption of the His bundle.

Electrophysiological and epicardial mapping studies are described in a patient without pre-excitation who had intractable recurrent paroxysmal supraventricular tachycardia. Electrophysiological studies revealed fixed VA conduction times during both rapid ventricular pacing and coupled ventricular stimulation. Catheter mapping of atrial activation during retrograde conduction and during induced paroxysmal supraventricular tachycardia revealed early distal coronary sinus activation (posterior left atrium) relative to the low septal, low lateral, and high lateral right atrium. These studies suggested the presence of a concealed left-sided bypass tract. The patient underwent surgical interruption of the His bundle for control of paroxysmal supraventricular tachycardia. Epicardial mapping of the atria (during ventricular pacing) confirmed the presence of a concealed left-sided bypass tract. Surgery produced antegrade av block (while retrograde conduction was maintained) and total cure of paroxysmal supraventricular tachycardia. This is the first reported case of a concealed retrograde extranodal pathway documented by epicardial mapping.

Prospective observations in patients with chronic bundle branch block and marked H-V prolongation.

Eighteen of 388 patients with chronic bundle branch block, studied electrophysiologically and followed prospectively, had H-V intervals of 80 msec or greater. Five patients were functional class I, five class II, seven class III, and one class IV. Follow-up ranged from 103 to 1919 days (mean 711 +/- 118). Three patients needed permanent pacing for the following indications: sino-atrial block, sinus bradycardia post-cardiac surgery, and 2 degrees block distal to the His bundle. Six patients died, three suddenly, and three nonsudden. The five initially asymptomatic patients are alive and without pacemakers (mean follow-up 732 +/- 139 days). Although marked H-V prolongation was associated with high morbidity and mortality in this small series, this was only in patients with symptomatic heart disease. Asymptomatic patients (five patients) had a benign clinical course. Prophylactic pacing would probably not modify clinical course in the former group, and is probably not indicated in the latter group. Longer follow-up will be needed for definitive prognostication.