Elena B. Sgarbossa

Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing

BACKGROUND: Standard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber pacemakers are believed to be more physiologic. However, it is not known whether either type of pacemaker results in superior clinical outcomes. METHODS: The Pacemaker Selection in the Elderly study was a 30-month, single-blind, randomized, controlled comparison of ventricular pacing and dual-chamber pacing in 407 patients 65 years of age or older in 29 centers. Patients received a dual-chamber pacemaker that had been randomly programmed to either ventricular pacing or dual-chamber pacing. The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey. RESULT: The average age of the patients was 76 years (range, 65 to 96), and 60 percent were men. Quality of life improved significantly after pacemaker implantation (P<0.001), but there were no differences between the two pacing modes in either the quality of life or prespecified clinical outcomes (including cardiovascular events or death). However, 53 patients assigned to ventricular pacing (26 percent) were crossed over to dual-chamber pacing because of symptoms related to the pacemaker syndrome. Patients with sinus-node dysfunction, but not those with atrioventricular block, had moderately better quality of life and cardiovascular functional status with dual-chamber pacing than with ventricular pacing. Trends of borderline statistical significance in clinical end points favoring dual-chamber pacing were observed in patients with sinus-node dysfunction, but not in those with atrioventricular block. CONCLUSION: The implantation of a permanent pacemaker improves health-related quality of life. However, the quality-of-life benefits associated with dual-chamber pacing as compared with ventricular pacing are observed principally in the subgroup of patients with sinus-node dysfunction.

Electrocardiographic Diagnosis of Evolving Acute Myocardial Infarction in the Presence of Left Bundle-Branch Block

BACKGROUND The presence of left bundle-branch block on the electrocardiogram may conceal the changes of acute myocardial infarction, which can delay both its recognition and treatment. We tested electrocardiographic criteria for the diagnosis of acute infarction in the presence of left bundle-branch block. METHODS The base-line electrocardiograms of patients enrolled in the GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) trial who had left bundle-branch block and acute myocardial infarction confirmed by enzyme studies were blindly compared with the electrocardiograms of control patients who had chronic coronary artery disease and left bundle-branch block. The electrocardiographic criteria for the diagnosis of infarction were then tested in an independent sample of patients presenting with acute chest pain and left bundle-branch block. RESULTS Of 26,003 North American patients, 131 (0.5 percent) with acute myocardial infarction had left bundle-branch block. The three electrocardiographic criteria with independent value in the diagnosis of acute infarction in these patients were an ST-segment elevation of 1 mm or more that was concordant with (in the same direction as) the QRS complex; ST-segment depression of 1 mm or more in lead V1, V2, or V3; and ST-segment elevation of 5 mm or more that was disconcordant with (in the opposite direction from) the QRS complex. We used these three criteria in a multivariate model to develop a scoring system (0 to 10), which allowed a highly specific diagnosis of acute myocardial infarction to be made. CONCLUSIONS We developed and validated a clinical prediction rule based on a set of electrocardiographic criteria for the diagnosis of acute myocardial infarction in patients with chest pain and left bundle-branch block. The use of these criteria, which are based on simple ST-segment changes, may help identify patients with acute myocardial infarction, who can then receive appropriate treatment.

Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities.

BACKGROUND The goal of the report was to study the long-term incidence and the independent predictors for chronic atrial fibrillation and stroke in 507 paced patients with sick sinus syndrome, adjusting for differences in baseline clinical variables with multivariate analysis. METHODS AND RESULTS From 1980 to 1989, we implanted 376 dual-chamber, 19 atrial, and 112 ventricular pacemakers to treat patients with sick sinus syndrome. After a maximum follow-up of 134 months (mean: 59 +/- 38 months for chronic atrial fibrillation, 65 +/- 37 months for stroke), actuarial incidence of chronic atrial fibrillation was 7% at 1 year, 16% at 5 years, and 28% at 10 years. Independent predictors for this event, from Coxs proportional hazards model, were history of paroxysmal atrial fibrillation (P < .001; hazard ratio [HR] = 16.84), use of antiarrhythmic drugs before pacemaker implant (P < .001; HR = 2.25), ventricular pacing mode (P = .003; HR = 1.98), age (P = .005; HR = 1.03), and valvular heart disease (P = .008; HR = 2.05). For patients with preimplant history of paroxysmal atrial fibrillation, independent predictors were prolonged episodes of paroxysmal atrial fibrillation (P < .001; HR = 2.56), long history of paroxysmal atrial fibrillation (P = .004; HR = 2.05), ventricular pacing mode (P = .025; HR = 1.69), use of antiarrhythmic drugs before pacemaker implant (P = .024; HR = 1.71), and age (P = .04; HR = 1.02). Actuarial incidence of stroke was 3% at 1 year, 5% at 5 years, and 13% at 10 years. Independent predictors for stroke were history of cerebrovascular disease (P < .001; HR = 5.22), ventricular pacing mode (P = .008; HR = 2.61), and history of paroxysmal atrial fibrillation (P = .037; HR = 2.81). CONCLUSIONS Development of chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome are strongly determined by clinical variables and secondarily by the pacing modality. Ventricular pacing mode predicts chronic atrial fibrillation in patients with preimplant paroxysmal atrial fibrillation but not in those without it.

Acute Myocardial Infarction and Complete Bundle Branch Block at Hospital Admission: Clinical Characteristics and Outcome in the Thrombolytic Era

OBJECTIVES We sought to assess the outcome of patients with acute myocardial infarction (MI) and bundle branch block in the thrombolytic era. BACKGROUND Studies of patients with acute MI and bundle branch block have reported high mortality rates and poor overall prognosis. METHODS The North American population with acute MI and bundle branch block enrolled in the Global Utilization of Streptokinase and t-PA [tissue-type plasminogen activator] for Occluded Coronary Arteries (GUSTO-I) trial was matched by age and Killip class with an equal number of GUSTO-I patients without conduction defects. RESULTS Of all 26,003 North American patients in GUSTO-I, 420 (1.6%) had left (n = 131) or right (n = 289) bundle branch block. These patients had higher 30-day mortality rates than matched control subjects (18% vs. 11%, p = 0.003, odds ratio [OR] 1.8) and were more likely to experience cardiogenic shock (19% vs. 11%, p = 0.008, OR 1.78) or atrioventricular block/asystole (30% vs. 19%, p < 0.012, OR 1.57) and to require ventricular pacing (18% vs. 11%, p = 0.006, OR 1.73). Bundle branch block also carried an independent 53% higher risk for 30-day mortality. Thirty-day mortality rates for patients with complete, partial and no reversion of the bundle branch block were 8%, 12% and 20%, respectively (two-tailed chi-square test for trend 5.61, p = 0.02, OR 0.34 for complete reversion, OR 0.55 for partial reversion). CONCLUSIONS Bundle branch block at hospital admission in patients with acute MI predicts in-hospital complications and poor short-term survival.

Non–Q-Wave Versus Q-Wave Myocardial Infarction After Thrombolytic Therapy Angiographic and Prognostic Insights From the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries–I Angiographic Substudy

BACKGROUND Although the stratification of patients with myocardial infarction into ECG subsets based on the presence or absence of new Q waves has important clinical and prognostic utility, systematic evaluation of the impact of thrombolytic therapy on the subsequent development and prognosis of non-Q-wave infarction has been limited to date. METHODS AND RESULTS We examined 12-lead ECG, coronary anatomy, left ventricular function, and mortality among 2046 patients with ST-segment elevation infarction from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries angiographic subset to gain further insight into the pathophysiology and prognosis of Q- versus non-Q-wave infarction in the thrombolytic era. Non-Q-wave infarction developed in 409 patients (20%) after thrombolytic therapy. Compared with Q-wave patients, non-Q-wave patients were more likely to present with lesser ST-segment elevation in a nonanterior location. The infarct-related artery in non-Q-wave patients was more likely to be nonanterior (67% versus 58%, P=.012) and distally located (33% versus 39%, P=.021). Early (90-minute, 77% versus 65%, P=.001) and complete (54% versus 44%, P<.001) infarct-related artery patency was greater among the non-Q-wave group. Non-Q-wave patients had better global (ejection fraction, 66% versus 57%; P<.0001) and regional left ventricular function (10 versus 24 abnormal chords, P=.0001). In-hospital, 30-day, 1-year, and 2-year (6.3% versus 10.1%, P=.02) mortality rates were lower among non-Q-wave patients. CONCLUSIONS The excellent prognosis among the subgroup of patients who develop non-Q-wave infarction after thrombolysis is related to early, complete, and sustained infarct-related artery patency with resultant limitation of left ventricular infarction and dysfunction.

The role of pacing modality in determining long-term survival in the sick sinus syndrome.

Symptomatic bradycardia secondary to sinus node dysfunction (the sick sinus syndrome) accounts for more than 50% of the current indications for permanent cardiac pacing [1]. Long-term survival in patients without pacing is similar to that of the general population [2], but patients with associated structural heart disease have a poorer outcome [3, 4], which is not changed by ventricular pacing [5-8]. Recently, it has been shown that atrial and dual-chamber pacemakers can improve short-term hemodynamics [9], exercise tolerance, and well-being [10, 11] in patients with the sick sinus syndrome when compared with fixed-rate ventricular pacing. It has also been suggested that these more physiologic pacing modes may decrease serious morbidity [12, 13] and improve survival [14]. This hypothesis was supported by several studies without internal controls [15-17], but in none of them were multivariable techniques used to adjust for baseline characteristics of patients treated with different pacing modalities, nor were large groups of patients followed for more than 5 years. Several authors no longer recommend single-chamber ventricular pacing as permanent therapy for the sick sinus syndrome [12, 18, 19]. However, it is still the most frequently used pacing modality in the United States [1] due to its wider availability, ease of implantation, and lower costs. Because of the recent emphasis on the monitoring of outcomes of medical interventions to determine their cost-effectiveness [20], we examined the potential benefit on long-term survival of physiologic pacing modalities in patients with the sick sinus syndrome. Methods Study Patients Between 1 January 1980 and 31 December 1989, we implanted an initial pacemaker in 507 adult patients (age > 18 years) with the sick sinus syndrome. The sick sinus syndrome was defined by the presence of inappropriate, persistent sinus bradycardia (rate < 50 beats/min), sinus pauses greater than 3 seconds, or sinoatrial block. Patients in permanent atrial fibrillation at the time of implant were excluded from the study. Patients with the sick sinus syndrome and complete atrioventricular (AV) block or type II second-degree AV block (unless resulting from AV junctional ablation in a patient who fulfilled criteria for the sick sinus syndrome before the procedure), were also excluded. All patients were symptomatic, required bradycardia-producing drugs for treatment of tachyarrhythmias, or both [21]. Documentation of symptomatic bradycardia (for example, its simultaneous occurrence with syncope), was considered desirable but not imperative for pacemaker implantation. Baseline variables describing cardiac disease, concomitant diseases, and electrocardiographic and echocardiographic findings were analyzed (Table 1). Concomitant diseases considered were systemic hypertension, diabetes, cerebrovascular disease, and peripheral vascular disease. Diagnostic criteria for diabetes were fasting glycemia greater than 140 mg/dL or chronic treatment with insulin or oral hypoglycemic agents. Cerebrovascular disease was defined by a history of stroke, transient ischemic attacks, carotid endarterectomy, or severe (70% or more) carotid stenosis by angiography. Peripheral vascular disease was defined by presence of intermittent claudication, aortic aneurysm, or a history of a peripheral revascularization procedure. Left ventricular function was assessed in 383 patients (76%) using contrast ventriculography (60%), echocardiography (34%), or radionuclide ventriculography (5%). Table 1. Clinical Characteristics Additionally, the initial pacing mode was analyzed. The pacing mode was selected in a nonrandomized fashion, based on the attending physicians appraisal of the patients needs. Ventricular pacemakers were implanted in 112 patients (22%), atrial pacemakers in 19 patients (4%), and dual-chamber pacemakers in 376 patients (74%). For the purposes of this analysis, atrial and dual-chamber pacemakers (defined as physiologic pacing) were compared with ventricular pacemakers. Due to technologic improvements during the time frame of the study, the year of implantation was the strongest determinant of type of pacemaker implanted, with a progressive increase in the number of dual-chamber pacemakers over time. Otherwise, patients with physiologic and ventricular pacemakers were similar for most of the variables analyzed, except for cerebrovascular and peripheral vascular disease (more prevalent in patients with ventricular pacemakers) and complex ventricular arrhythmia (more prevalent in patients with physiologic pacemakers) (see Table 1). Only 31 (6%) of the devices had sensors to provide rate responsiveness, too few to justify a separate statistical analysis. The mean AV delay that was programmed at discharge in patients with dual-chamber pacemakers was 198 43 msec. The mean PR interval in this subgroup was 180 52 msec. The relatively long AV delay was programmed to allow for spontaneous ventricular activation whenever possible. Follow-up Patients were followed for a mean of 66 38 months. Follow-up began on the date of pacemaker implant and ended on the date of the patients death or the end of the study (31 December 1990). Survival status, causes of death, and reprogramming of the initial pacing mode were ascertained through review of medical records, through questionnaires completed by the patients private physician, and through telephone interviews with the patients or their families. Follow-up was complete in 98.5% of the patients. Eight patients were lost to follow-up after a mean of 56 months and had their follow-up censored at time of last contact. Causes of death were grouped as cardiovascular-related (sudden death, congestive heart failure, refractory ventricular tachyarrhythmia, myocardial infarction, stroke, peripheral embolism), noncardiovascular (any other documented cause), or unknown. Statistical Analysis Continuous variables are presented as mean 1 SD. Actuarial curves for total and cardiovascular mortality were calculated with the method of Kaplan and Meier. The primary analysis was done using an intention-to-treat approach. In a secondary analysis, patients were censored at the time of crossover to the alternative pacing mode (that is, upgrading from ventricular to dual-chamber pacing or permanent reprogramming of a physiologic pacing mode to a ventricular pacing mode). The expected survival for an age- and sex-matched general population was compiled from data of the National Vital Statistics System. A standardized score (z score) was calculated to test for differences in survival between the study group and the general population at each yearly interval (year 1 to year 10). To adjust for the multiple comparisons, a P value 0.005 was considered significantly different (the Bonferroni correction). Analyzed variables were screened by univariate statistical methods to identify those associated with total and cardiovascular mortality. Kaplan-Meier actuarial curves for survival were constructed for each variable on the basis of natural dichotomies (for example, the presence or absence of coronary artery disease) or stratifications in the data (for example, New York Heart Association functional class) and were compared by means of the log-rank test. Multivariable regression analysis, done with the Cox proportional-hazards model, was applied to all variables that had at least marginal univariate predictive value (P < 0.10). The variables were entered into the regression equation in a forward stepwise manner. Variables with statistically independent predictive value (defined as P < 0.05) were identified, and their hazard ratio (that is, the relative risk attributable to various levels of each variable, all other variables being unchanged) was estimated. The assumption of proportional hazards for the exposure of interest was tested, and it was not violated. Statistical analyses were done using EGRET software (Statistics and Epidemiologic Research Corporation, Seattle, Washington) [22]. Covariates-adjusted curves for total survival according to pacing modality were constructed with the corrected group prognostic curves method described by Lee and colleagues [23]. Results Total and Cardiovascular Survival During the follow-up period, 130 patients (26%) died (46 patients with ventricular pacemakers and 84 patients with physiologic pacemakers). Seventy-seven patients (59%) died from cardiovascular-related causes (26 patients with ventricular pacemakers and 51 patients with physiologic pacemakers), including congestive heart failure (48%), sudden death (23%), miscellaneous (for example, myocardial infarction [21%]), and stroke (8%). Causes of death were noncardiovascular in 41 patients (32%) and unknown in 12 patients (9%). Actuarial survival probability for the entire study group was 0.95 at 1 year (CI, 0.93 to 0.97); 0.80 at 5 years (CI, 0.76 to 0.83); and 0.61 at 10 years (CI, 0.55 to 0.67). Freedom from cardiovascular-related mortality was 0.96 (CI, 0.94 to 0.98); 0.88 (CI, 0.84 to 0.91); and 0.76 (CI, 0.70 to 0.81), at 1, 5, and 10 years, respectively. Expected survival for an age- and sex-matched general U.S. population was 0.97 at 1 year, 0.84 at 5 years, and 0.70 at 10 years. Differences were not statistically significant during the first 5 years of follow-up. After the fifth year, survival in the study group was consistently poorer (P = 0.002 at 6 years; P = 0.004 at 10 years) (Figure 1). Figure 1. Actuarial survival in the study group compared with the expected survival for an age- and gender-matched general population. P P Prediction of Total and Cardiovascular Mortality Using Univariate Analysis Qualitative overlap occurred between univariate predictors of total and cardiovascular death (Table 2). Although the ventricular pacing mode was associated with 43% higher mortality than was physiologic pacing (total death: P = 0.053; hazard ratio = 1.43; CI, 0.99 to 2.07; cardiovascular death: P = 0.15; ha

Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis.

We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone 99mTc sestamibi single-photon emission computed tomography before and 6 ± 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio ×100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion.

Predictors and Clinical Impact of Atrial Fibrillation After Pacemaker Implantation in Elderly Patients Treated with Dual Chamber Versus Ventricular Pacing

The Pacemaker Selection in the Elderly (PASE) trial was a prospective, multicenter, single blind, randomized comparison of single chamber, rate adaptive, ventricular pacing (VVIR) with dual chamber, rate adaptive pacing (DDDR) in 407 patients aged ≥65 years (mean 76 ± 7 years, 60% male) with standard bradycardia indications for dual chamber pacemaker implantation. The incidence, predictors, and clinical consequences of atrial fibrillation (AF) developing after pacemaker implantation in the PASE trial were studied prospectively. During a median follow‐up of 18 months, AF developed in 73 (18%) patients. Kaplan‐Meier estimated cumulative incidences of AF in patients with sinus node dysfunction (n = 176) at 18 months were 28% in the VVIR and 16% in the DDDR groups (P = 0.08). After adjustment for other clinical variables using a Cox multivariate regression model, randomization to VVIR compared with DDDR pacing mode among patients with sinus node dysfunction was independently associated with a 2.6‐fold increased relative risk (RR) of developing AF after pacemaker implantation (P = 0.01). Other independent clinical risk factors for development of postimplant AF included a preimplant history of hypertension (P = 0.02) or supraventricular tachyarrhythmias (P < 0.04). Patients who developed AF had similar health related quality of life scores and cardiovascular functional status after 18 months of pacing as patients who remained free of AF. The RR of death, stroke, or heart failure hospitalization was not increased in patients who developed AF. Thus, in the elderly patients with sinus node dysfunction requiring permanent pacing, DDDR pacing mode protected against the development of AF. However, development of AF after pacemaker implantation in this population was not associated with a significant impact on quality‐of‐life, functional status, or other clinical endpoints during 18 months of follow‐up. (PACE 2003; 26:2000–2007)

Incidence and predictors of syncope in paced patients with sick sinus syndrome.

In spite of a normal pacemaker/unction, syncope still occurs in some patients with sick sinus syndrome (SSSJ. Causes often remain unknown. To identify predictors and etiologies of this bothersome symptom, we studied 507 patients who received atrial, ventricular, and dual‐chamber pacemakers for SSS. During a mean follow‐up of 62 ± 38 months, actuarial incidence of syncope was 3% at 1 year, 8% at 5 years, and 13% at 10 years. Causes were vasovagal (18%), orthostatic hypotension (25.5%), rapid atrial tachyarrhythmias (11.5%), ventricular tachycardia (5%), acute myocardial ischemia (2.5%), and pacemaker/lead malfunction (6.5%), In 13 patients (29.5%), syncope remained unexplained. The only preimplant predictor for syncope was syncope as primary indication for pacemaker implant. Electrocardiographic correlation with bradycardia was not a predictor of relief of syncope during the follow‐up. In conclusion: (1) syncope in paced patients with SSS has multiple etiologies and may be multifactorial; (2) the only predictor of syncope after pacemaker implant is the occurrence of preimplant syncope as the main indication for pacing; (3) extensive Holier monitoring is not useful to document bradycardic origin of syncope nor to predict its recurrence; (4) SSS probably overlaps with other entities such as autonomic dysfunction, vasovagal syncope, carotid sinus hypersensitivity, and venous pooling, which would provide an explanation for recurrent syncope in patients with normal pacemaker function.

Thrombolysis and Q Wave Versus Non-Q Wave First Acute Myocardial Infarction: A GUSTO-I Substudy ☆

OBJECTIVES We assessed the outcomes of patients with a first myocardial infarction with ST segment elevation, with and without the development of abnormal Q waves after thrombolysis. BACKGROUND Prethrombolytic era studies report conflicting short-versus long-term mortality in the overall non-Q wave population, probably related to its heterogeneity. METHODS Patients with no electrocardiographic (ECG) confounding factors or evidence of previous infarction were included. Q wave infarction was defined as a Q wave duration > or = 30 ms in lead aVF; R wave > or = 40 ms in lead V1; any Q wave or R wave < or = 10 ms and < or = 0.1 mV in lead V2; or Q wave > or = 40 ms in at least two of the following leads: I, aVL, V4, V5 or V6. In-hospital clinical events and mortality at 30 days and 1 year were assessed. RESULTS No Q waves developed in 4,601 (21.3%) of the 21,570 patients. This group comprised more women and had a lower Killip class, lower weight and less anterior baseline ST elevation. The non-Q wave group had less in-hospital cardiogenic shock (2.1% vs. 3.3%, p < 0.0001), less heart failure (8.5% vs. 13.9%, p < 0.0001) and a trend toward less stroke (0.7% vs. 1.0%, p = 0.07) but an increased use of angioplasty (28% vs. 24%, p = 0.0001). The unadjusted mortality rate in the non-Q wave group was lower at 30 days (0.9% vs. 1.8%, p = 0.0001) and 1 year (2.7% vs. 4.2%, p = 0.0001), as was the adjusted 30-day mortality rate (4.8% vs. 5.3%, p < 0.0001). CONCLUSIONS Patients with no ECG confounding factors or evidence of previous infarction who do not develop Q waves after thrombolysis have a better 30-day and 1-year prognosis than patients with a Q wave infarction.