Richard S. Crampton

Effectiveness and limitations of β-blocker therapy in congenital long-QT syndrome

BACKGROUND beta-blockers are routinely prescribed in congenital long-QT syndrome (LQTS), but the effectiveness and limitations of beta-blockers in this disorder have not been evaluated. METHODS AND RESULTS The study population comprised 869 LQTS patients treated with beta-blockers. Effectiveness of beta-blockers was analyzed during matched periods before and after starting beta-blocker therapy, and by survivorship methods to determine factors associated with cardiac events while on prescribed beta-blockers. After initiation of beta-blockers, there was a significant (P<0.001) reduction in the rate of cardiac events in probands (0.97+/-1.42 to 0.31+/-0.86 events per year) and in affected family members (0. 26+/-0.84 to 0.15+/-0.69 events per year) during 5-year matched periods. On-therapy survivorship analyses revealed that patients with cardiac symptoms before beta-blockers (n=598) had a hazard ratio of 5.8 (95% CI, 3.7 to 9.1) for recurrent cardiac events (syncope, aborted cardiac arrest, or death) during beta-blocker therapy compared with asymptomatic patients; 32% of these symptomatic patients will have another cardiac event within 5 years while on prescribed beta-blockers. Patients with a history of aborted cardiac arrest before starting beta-blockers (n=113) had a hazard ratio of 12.9 (95% CI, 4.7 to 35.5) for aborted cardiac arrest or death while on prescribed beta-blockers compared with asymptomatic patients; 14% of these patients will have another arrest (aborted or fatal) within 5 years on beta-blockers. CONCLUSIONS beta-blockers are associated with a significant reduction in cardiac events in LQTS patients. However, syncope, aborted cardiac arrest, and LQTS-related death continue to occur while patients are on prescribed beta-blockers, particularly in those who were symptomatic before starting this therapy.

Prediction of cardiac events after uncomplicated myocardial infarction: a prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography.

The ability of predischarge quantitative exercise thallium-201 (201T1) scintigraphy to predict future cardiac events was evaluated prospectively in 140 consecutive patients with uncomplicated acute myocardial infarction; the results were compared with those of submaximal exercise treadmill testing and coronary angiography. High risk was assigned if scintigraphy detected 201T1 defects in more than one discrete vascular region, redistribution, or increased lung uptake, if exercise testing caused ST segment depression greater than or equal to 1 mm or angina or if angiography revealed multivessel disease. Low risk was designated if scintigraphy detected a single-region defect, no redistribution, or no increase in lung uptake, if exercise testing caused no ST segment depression or angina, or if angiography revealed single-vessel disease or no disease. By 15 +/- 12 months, 50 patients had experienced a cardiac event; seven died (five suddenly), nine suffered recurrent myocardial infarction, and 34 developed severe class III or IV angina pectoris. Compared with that of patients at low risk, the cumulative probability of a cardiac event was greater in high-risk patients identified by scintigraphy (p less than .001), exercise testing (p = .011), or angiography (p = .007). Scintigraphy predicted low-risk status better than exercise testing (p = .01) or angiography (p = .05). Each predicted mortality with equal accuracy. However, scintigraphy was more sensitive in detecting patients who experienced reinfarction or who developed class III or IV angina. When all 50 patients with events were combined, scintigraphy identified 47 high-risk patients (94%), whereas exercise-induced ST segment depression or angina detected only 28 (56%) (p less than .001). The presence of multivessel disease as assessed by angiography identified nine more patients with events than exercise testing (p = .06). However, the overall sensitivity of angiography was lower than that of scintigraphy (71% vs 94%; p less than .01) because three patients who experienced reinfarction and 10 who developed class III or IV angina had single-vessel disease. Importantly, 12 (92%) of these 13 patients with single-vessel disease who had an event exhibited redistribution on scintigraphy. These results indicate that (1) submaximal exercise 201T1 scintigraphy can distinguish high- and low-risk groups after uncomplicated acute myocardial infarction before hospital discharge; (2) 201T1 defects in more than one discrete vascular region, presence of delayed redistribution, or increased lung thallium uptake are more sensitive predictors of subsequent cardiac events than ST segment depression, angina, or extent of angiographic disease; and (3) low-risk patients are best identified by a single-region 201T1 defect without redistribution and no increased lung uptake.

Value of early two dimensional echocardiography in patients with acute myocardial infarction

Abstract Seventy-five consecutive patients with acute myocardial infarction underwent two dimensional echocardiography 7.9 ±3.1 hours after admission (1) to determine if this procedure can detect regional left ventricular asynergy in an unselected series of patients; (2) to evaluate the relation of asynergy outside the electrocardiographic infarct zone to clinical events and coronary anatomic findings; and (3) to determine whether the procedure can identify patients at high risk for cardiogenic shock, before the onset of hemodynamic deterioration. For purposes of analysis, the left ventricle was divided into 11 segments; individual segments were evaluated for systolic wall motion and thickening, and a wall motion index was calculated as a measure of global left ventricular performance. Technically satisfactory two dimensional echographic studies were obtained in all 75 patients. Of 825 possible segments in the 75 patients, 795 (96 percent) or 10.6 segments per patient were deemed adequate for analysis. Akinesia or dyskinesia was detected in at least one segment in all patients, including 15 (20 percent) who underwent imaging within 4 hours of the onset of symptoms and 19 (25 percent) with nontransmural infarction. Severe wall motion abnormalities outside the infarct zone were observed in 47 percent of patients and correlated with a greater prevalence of death (p = 0.03), cardiogenic shock (p Thus, two dimensional echocardiography performed soon after admission to the coronary care unit is technically feasible, provides useful information concerning regional and global left ventricular function and offers important predictive information about patients early in acute myocardial infarction.

Analysis of pacemaker malfunction and complications of temporary pacing in the coronary care unit

The medical records of 100 patients who received 113 temporary transvenous pacemakers were reviewed to determine the incidence of complications and malfunction. Malfunction, defined as failure to capture or sense, or both, occurred in 42 (37 percent) of 113 temporary pacemakers. The initial malfunction occurred within 24 hours in 21 (50 percent) and within 48 hours in 36 (86 percent) of the 42 pacemakers. Although the incidence of malfunction was not significantly different for brachial and femoral venous pacing catheters, 7 (37 percent) of 19 brachial venous pacemakers required repositioning or replacement compared with 8 (9 percent) of 91 femoral venous catheters (p = 0.005). Thirty-seven complications occurred in 23 (20 percent) of 113 episodes of pacing; ventricular tachycardia during catheter insertion, fever and phlebitis were the most common complications. No complication resulted in death. The incidence of complications and perforation was greater for brachial than for femoral venous pacemakers (p less than 0.05). Sepsis, local infection and pulmonary embolus occurred only with femoral venous pacemakers. Sepsis, phlebitis and pulmonary embolus were more common with temporary pacemakers in place for 7 hours or longer (p = 0.04). Recognition to the problems peculiar to each pacing catheter site and shortening the duration of pacing should help minimize problems with temporary pacing.

Predicting the extent and location of coronary artery disease during the early postinfarction period by quantitative thallium-201 scintigraphy

The ability of quantitative thallium-201 scintigraphy to predict the extent and location of coronary artery disease before hospital discharge after acute myocardial infarction was evaluated in 52 patients. All patients underwent coronary angiography and serial thallium-201 imaging either at rest (10 patients) or after submaximal exercise stress (42 patients; target heart rate 120 beats/min). Two or three vessel disease was designated if abnormal thallium-201 uptake or washout patterns, or both, were seen in two or three vascular segments, respectively. Of 156 vessels analyzed in the 52 patients, 91 stenoses of 70 percent or greater were found by angiography. Seventy-four (81 percent) of these were predicted by scintigraphy. The specificity of scintigraphy for identifying vessel stenoses was 92 percent. Sensitivity for detecting and localizing stenoses supplying an infarct zone was 96 percent compared with 62 percent for stenoses supplying myocardium remote from the acute infarct. Perfusion abnormalities were more frequently seen in the distribution of vessels with severe (90 percent or greater) stenoses than in those with moderate (70 to 90 percent) stenoses (87 versus 53 percent, p less than 0.01). Scintigraphy detected a greater proportion of left anterior descending and right coronary arterial stenoses than circumflex stenoses (91 and 87 versus 63 percent, respectively, p less than 0.006). In the 42 patients who underwent submaximal exercise testing, multivariate analysis of 23 clinical and laboratory variables identified multiple thallium-201 defects as the best predictor of multivessel disease. The predictive accuracy of exercise-induced S-T segment depression was only 45 percent compared with 88 percent (p less than 0.05) for thallium-201 scintigraphy. Thus, 2 weeks after myocardial infarction, exercise thallium-201 scintigraphy is useful for predicting the extent and location of coronary artery disease, particularly stenoses in the left anterior descending and right coronary arteries. Moreover, thallium-201 imaging at rest is reliable in assessing the extent of coronary disease in hospitalized patients who cannot undergo exercise testing because of unstable angina, uncompensated heart failure, poorly controlled arrhythmias or physical limitations.

Prolonged QT interval at onset of acute myocardial infarction in predicting early phase ventricular tachycardia

The prospectively assessed time course of changes in ventricular repolarization during acute myocardial infarction (AMI) is reported in 32 patients admitted 2.0 +/- 1.8 (SD) hours after AMI onset. The initial corrected QT interval (QTc) upon hospitalization was longer (0.52 +/- 0.07 seconds) in the 14 patients developing ventricular tachycardia (VT) within the first 48 hours as compared to QTc (0.47 +/- 0.03 seconds) in the eight patients with frequent ventricular premature beats (VPBs) and to QTc (0.46 +/- 0.03 seconds) in the 10 patients with infrequent VPBs (p less than 0.001; analysis of variance). By the fifth day after AMI onset, the QTc shortened significantly only in the VT group, suggesting a greater initial abnormality of repolarization in these patients. All 32 patients had coronary angiography, radionuclide ventriculography, and myocardial perfusion scintigraphy before hospital discharge. Significant discriminating factors related to early phase VT in AMI included initially longer QT and QTc intervals, faster heart rate, higher peak serum levels of creatine kinase, acute anterior infarction, angiographically documented proximal stenosis of the left anterior descending coronary artery, and scintigraphic evidence of hypoperfusion of the interventricular septum. Prior infarction, angina pectoris, hypertension, multivessel coronary artery disease, and depressed left ventricular ejection fraction did not provide discrimination among the three different ventricular arrhythmia AMI groups. We conclude that (1) the QT interval is frequently prolonged early in AMI, (2) the initial transiently prolonged ventricular repolarization facilitates and predicts complex ventricular tachyarrhythmias within the first 48 hours of AMI, (3) jeopardized blood supply to the interventricular septum frequently coexists, and (4) therapeutic enhancement of rapid recovery of the ventricular repolarization process merits investigation for prevention of VT in AMI.

Accepted, controversial, and speculative aspects of ventricular defibrillation

I N 1775 Abildgaard described a series of experiments in which electric shocks rendered chickens “lifeless” and subsequent shocks resuscitated the animals.‘92 One hundred twentyfive years later, Prtvost and Batelli induced ventricular fibrillation (VF) with alternating current and with occlusion of the left coronary artery. They then terminated VF by discharge of a capacitor.3*4 Zipes has summarized subsequent observations and has contributed an important group of experiments that clearly indicate that depolarizing a sufficient mass (about threequarters) of ventricular myocardium alters the conditions or the mechanisms that promote and sustain VF and thereby defibrillates the ventricles.‘*6 Resnekov’s excellent text on direct current shock describes the historic contributions of Kouwenhoven, Ferris, King, Wiggers, Wtgria, Gurvich, Yunyev, Peleska, Tsukerman, Beck, Lown, Zoll, and their colleagues.’ This article reviews, updates, and correlates present knowledge about some of the factors that are known or thought to influence ventricular defibrillation.

Effect of intravenous magnesium sulfate on supraventricular tachycardia

Abstract In 1943, Boyd and Scherf 1 reported magnesium sulfate (MgSO 4 ) to be effective in the treatment of supraventricular tachycardia (SVT). Recently, the infusion of MgSO 4 has been shown to increase the atrio-His interval and atrioventricular nodal refractoriness. 2 However, MgSO 4 has not yet been systematically examined for its effect on SVT. This study was designed to evaluate the efficacy and clinical tolerance of MgSO 4 in the treatment of SVT at the bedside and in the electrophysiology laboratory.

Determinants of ventricular defibrillation in adults.

Conventional defibrillators which stored no more than 400 J and used damped sine wave pulses defibrillated 240 of 253 (95%) episodes of ventricular fibrillation (VF) in 94 prospectively assessed resuscitations in 88 adults. Shocks of 80-240 J (under 3 J/kg) delivered to the chest wall defibrillated more often than higher energy levels. Defibrillation rate did not correlate with weight. Defibrillation was determined by the diagnosis and setting in which VF occurred. Patients with acute myocardial infarction (AMI) and primary VF or with coronary disease and no AMI defibrillated more easily than patients with AMI and secondary VF or with no coronary disease. VF in a terminal patient (agonal VF) defibrillated less often than VF in other clinical situations. Age, weight, delivered energy, duration of pulse wave, and duration of VF had little, if any, influence on rate of defibrillation. These data fail to support the use of more expensive, high-output defibrillators sold by 11 of 14 American manufacturers.

Acute myocardial infarction associated with single vessel coronary artery disease: An analysis of clinical outcome and the prognostic importance of vessel patency and residual ischemie myocardium☆

Abstract The long-term outcome and the significance of residual ischemie myocardium, as assessed by predischarge exercise thallium scintigraphy and vessel patency, were studied in 97 patients with single vessel coronary artery disease by angiography 12 ± 4 days after uncomplicated myocardial infarction. During a mean follow-up period of 39 ± 17 months, ηρ patients died, 6 (6%) had a recurrent nonfatal infarction and 25 (26%) experienced rapidly progressive angina requiring hospitalization. Although neither exercise-induced angina nor ST segment depression was predictive of a recurrent cardiac event, the mean number of infarct zone scan segments showing thallium redistribution (1.0 ± 1.0 versus 0.5 ± 0.8, p = 0.01) and the percent of patients with infarct zone redistribution (61 versus 39%, p = 0.05) were greater in those patients who experienced a late ischemie event. Kaplan-Meier analysis demonstrated a tower event-free survival rate in patients with redistribution (n = 45) than in those without redistribution (n = 52) (p = 0.019). Although no patient received immediate ihrombolytic therapy, the infarct-related vessel was angiographically patent in 40 patients (41%). Vessel patency did not influence event-free survival, although a patent vessel, as compared with an occluded vessel, was associated with a greater prevalence of nun-Q wave infarction (58 versus 21%. p In summary, uncomplicated myocardial infarction in patients with single vessel coronary artery disease is associated with a very low incidence of subsequent death and reinfarction. The presence of infarct zone thallium redistribution), compared with its absence, is predictive of a higher cardiac eyent rate. These data should be considered when recommending prophylactic percutaneous transluminal angioplasty after uncomplicated myocardial infarction in asymptomatic patients with single vessel coronary disease. On the basis of these results, future randomized trials designed to evaluate the therapeutic efficacy of revascuiarization in asymptomatic postinfarction patients with single vessel disease should limit enrollment to those patients with residual ischemia located within the infarct zone.