Left ventricular geometry and operative mortality in patients undergoing mitral valve replacement.

BACKGROUND: Distortion of left ventricular (LV) shape is often associated with LV dysfunction and is thought to be an independent predictor of survival in patients with coronary disease. HYPOTHESIS: The purpose of this study was to examine the relationship between LV geometry and hospital mortality in patients with mitral regurgitation (MR) undergoing mitral valve surgery. METHODS: A consecutive series of patients (aged 68+/-12 years, 47% men) (n = 149) with MR who underwent cardiac catheterization, left ventriculography, and mitral valve surgery from 1995 to 1996 at Mount Sinai Medical Center was studied. Left ventriculograms, clinical records, and hemodynamics were reviewed. Left ventricular volumes and ejection fraction were calculated using standard techniques. Left ventricular shape in diastole and systole was evaluated using the sphericity index, which is defined as the end-systolic LV volume (x 100) divided by the volume of a sphere whose diameter is equal to the LV long axis. RESULTS: In the patients studied, the etiology of mitral insufficiency was mitral valve prolapse in 40.9%, ischemic heart disease in 40.3%, rheumatic heart disease in 11.4%, and prosthetic valvular dysfunction in 7.4%. The average ejection fraction was 65%+/-17. Systolic sphericity index (SSI) was 36%+/-15 in patients who died, compared with 25%+/-11 in patients who lived (p < 0.001). A multivariate model was constructed using hemodynamic and angiographic indices derived during preoperative cardiac catheterization. Systolic sphericity index (odds ratio = 1.6 for each point increase, p < 0.01) was found to be an independent predictor of postoperative survival in the global population, as well as in patients with coronary disease (p<0.01). CONCLUSION: Left ventricular geometry is an independent angiographic risk factor for survival following mitral valve replacement. Sphericity index is a simple method for assessing LV geometry which should be calculated in patients as part of risk stratification.

Update in internal medicine.

More than 500,000 new medical articles are published every year and available time to keep updated is scarcer every day. Nowadays, the task of selecting useful, consistent, and relevant information for clinicians is a priority in many major medical journals. This review has the aim of gathering the results of the most important findings in clinical medicine in the last few years. It is focused on results from randomized clinical trials and well-designed observational research. Findings were included preferentially if they showed solid results, and we avoided as much as possible including only preliminary data, or results that included only non-clinical outcomes. Some of the most relevant findings reported here include the significant benefit of statins in patients with coronary artery disease even with mean cholesterol level. It also provides a substantial review of the most significant trials assessing the effectiveness of IIb/IIIa receptor blockers. In gastroenterology many advances have been made in the H. pylori eradication, and the finding that the cure of H. pylori infection may be followed by gastroesophageal reflux disease. Some new antivirals have shown encouraging results in patients with chronic hepatitis. In the infectious disease arena, the late breaking trials in anti-retroviral disease are discussed, as well as the new trends regarding antibiotic resistance. This review approaches also the role of leukotriene modifiers in the treatment of asthma and discusses the benefit of using methylprednisolone in patients with adult respiratory distress syndrome, among many other advances in internal medicine.

The mode selection trial (MOST) in sinus node dysfunction: design, rationale, and baseline characteristics of the first 1000 patients.

BACKGROUND: More than 200,000 permanent pacemakers will be implanted in the United States in 2000 at a cost of more than $2 billion. Sick sinus syndrome (SSS) will likely account for approximately half of all cases necessitating implantation. Pacemaker technology permits the selection of ventricular (single-chamber) or dual-chamber devices. However, clinical and outcomes data are inadequate to support a clear recommendation that one or the other type of device be used. METHODS: The Mode Selection Trial (MOST) is a single-blind study supported by the National Heart, Lung, and Blood Institute designed to enroll 2000 patients with SSS. All patients will receive a DDDR pacemaker programmed to VVIR or DDDR before implantation. The average time of follow-up will be 3 years. MOST has a >90% power to detect a 25% reduction in the primary end point-nonfatal stroke or total (all cause) mortality-in the DDDR-treated group. Secondary end points will include health-related quality of life and cost effectiveness, atrial fibrillation, and development of pacemaker syndrome. Prespecified subgroups for analysis will include women and the elderly. Enrollment was completed in October 1999, with a total of 2010 patients. RESULTS: The median age of the first 1000 enrolled patients is 74 years, with 25% of patients 80 years or older. Women comprise 49%, and 17% are nonwhite, predominantly black (13%). Before pacemaker implantation, 22% of patients reported a history of congestive heart failure, 11% coronary angioplasty, and 25% coronary bypass surgery. Supraventricular tachycardia including atrial fibrillation was present in 53% of patients. A prior stroke was reported by 12%. Antiarrhythmic therapy was in use in 18% of patients. CONCLUSIONS: MOST will fill the clinical need for carefully designed prospective studies to define the benefits of dual-chamber versus single-chamber ventricular pacing in patients with SSS. The MOST population is typical of the overall pacemaker population in the United States. Thus the final results of MOST should be clinically generalizable.

Clinical characteristics of patients intolerant to VVIR pacing.

The incidence and clinical predictors of the development of intolerance to VVIR pacing have not been extensively studied in prospective long-term randomized trials comparing different pacing modes. The frequency and clinical factors predicting intolerance to ventricular pacing are controversial. The Pacemaker Selection in the Elderly (PASE) Trial enrolled 407 patients aged >/=65 years in a 30-month, single-blind, randomized, controlled comparison of quality of life and clinical outcomes with ventricular pacing and dual-chamber pacing in patients undergoing dual-chamber pacemaker implantation for standard clinically accepted indications. We reviewed the clinical, hemodynamic, and electrophysiologic variables at the time of pacemaker implantation in 204 patients enrolled in the PASE trial and randomized to the VVIR mode, some of whom subsequently required crossover (reprogramming) to DDDR pacing. During a median follow-up of 555 days, 53 patients (26%) crossed over from VVIR to DDDR pacing. A decrease in systolic blood pressure during ventricular pacing at the time of pacemaker implantation (p = 0.001), use of beta blockers at the time of randomization (p = 0.01), and nonischemic cardiomyopathy (p = 0.04) were the only variables that predicted crossover in the Cox multivariate regression model. After reprogramming to the dual-chamber mode, patients showed improvement in all aspects of quality of life, with significant improvements in physical and emotional role. The high incidence of crossover from VVIR to DDDR pacing along with significant improvements in quality of life after crossover to DDDR pacing strongly favors dual-chamber pacing compared with single-chamber ventricular pacing in elderly patients requiring permanent pacing.

Beneficial effects of an open artery on left ventricular remodeling after myocardial infarction.

During the last 2 decades researchers have developed a clearer understanding of the pathophysiology of acute myocardial infarction (AMI). The use of thrombolysis and coronary angioplasty early in the course of AMI salvages myocardium and preserves left ventricular function, which results in improved survival rates. Late reperfusion after AMI, however, may provide beneficial effects on long-term prognosis, especially owing to attenuation of left ventricular remodeling. This article reviews the evidence of the benefits of an open infarct-related artery on left ventricular remodeling after AMI.

Ejection fraction by radionuclide ventriculography and contrast left ventriculogram. A tale of two techniques. SAVE Investigators. Survival and Ventricular Enlargement.

OBJECTIVES: We assessed the abilities of two methods to measure ejection fraction (EF)-radionuclide ventriculography (RVG) and contrast left ventriculography (Cath-EFa) to predict cardiovascular events. BACKGROUND: Both RVG and Cath-EFa are commonly used methods to measure left ventricular performance and assess prognosis. Their comparative abilities to predict clinical events have not been reported. METHODS: Both RVG EF and Cath-EFa were measured within 16 days of myocardial infarction (MI) in 688 patients. The results were divided into terciles. Prognosis by terciles was assessed for each technique. A multivariate analysis was performed to determine which EF measurement was a better predictor of prognosis. RESULTS: Average RVG-EF was 32%+/-7, while Cath-EFa was 42%+/-10. Both RVG and Cath-EFa were poorly correlated (R=0.42). Event rate declined across terciles with increasing EF for both techniques (events in lowest to highest tercile of Cath-EFa 40.7%, 25.9%, 11.6%, p < 0.001; and RVG-EF 39.9%, 26.1%, 15.6%, p < 0.001). There was concordance of terciles in 303 of 688 patients (44%). When patients in the highest RVG terciles were in the highest Cath-EFa tercile, the event rate was 7%. However, when patients in the highest RVG terciles were in the lowest Cath-EFa tercile, the event rate was 19%. Both Cath-EFa (p < 0.001) and RVG-EF (p < 0.001) were independent predictors of cardiovascular events. CONCLUSIONS: Ejection fraction measured by RVG or during catheterization is a valuable tool in the risk stratification of postinfarct patients. When disagreement is present between clinical impression and measurement by either method, the use of an alternative measurement is warranted and complementary.

Age-related differences in management of heart disease: a study of cardiac medication use in an older cohort. Pacemaker Selection in the Elderly (PASE) Investigators.

BACKGROUND: Previous studies have suggested suboptimal use of cardiac medications for secondary prevention after myocardial infarction (MI) and atrial fibrillation (AF), especially among older people. OBJECTIVE: To determine whether patients older than 75 years are less likely than those aged 65 to 74 to be prescribed medications with evidence-based indications, including angiotensin-converting enzyme (ACE) inhibitors for left ventricular dysfunction (LVD) and/or diabetes mellitus (DM), aspirin and/or beta-blockers for those with a history of MI, and warfarin for chronic AF. DESIGN: A retrospective cohort study. SETTING: Twenty-nine hospitals, predominantly tertiary-care institutions. PARTICIPANTS: A total of 407 patients randomized to ventricular or dual-chamber pacing from February 26, 1993, to September 30, 1994, in the Pacemaker Selection in the Elderly (PASE) trial. MEASUREMENTS: A review of the patient's medical history and a physical exam at study enrollment, three follow-up timepoints, and a study closeout. RESULTS: Patients older than 75 years with LVD and/or DM were less likely to be prescribed ACE inhibitors (OR = .56 (0.31-1.00)); patients older than 75 with a history of MI were less likely to be taking aspirin (OR = .43 (0.19-.95)), and patients older than 75 with AF were less likely to be prescribed warfarin (OR = .18 (0.05-.61)). Patients older than 75 years of age with any or all of the conditions studied were less likely to be prescribed indicated medications than those ages 65 to 74 (OR = .35 (0.18-.70)), after controlling for between-group differences in comorbidity, gender, and number of noncardiac medications. CONCLUSION: Older age is a significant independent negative correlate of evidence-based cardiac medication use in this cohort. Causes for this finding need to be explored.

[Ventricular geometry and heart failure]. / Geometría ventricular e insuficiencia cardíaca.

In the last years there has been an appreciation of the importance of left ventricular geometry. After a period, in the sixties and seventies, that the interest was focused on cardiac physiology and the left ventricular geometry role about this subject, new studies are available on clinical significance of normal or distorted left ventricular shape. New assessment methods of ventricular geometry have been described. The use of simple measurements to assess ventricular geometry has allowed to know the clinical value of the shape distortion in patients with heart failure. The suspicion that left ventricular shape change to sphericity has prognosis value, has raised the interest about this subject. Whether distortion of left ventricular shape is an even better parameter than cardiac function indices normally used is under consideration. Moreover, new surgical therapies have been developed in an attempt to improve the ventricular geometry and to get better clinical prognosis in patients with heart failure.

Complications of dual chamber pacemaker implantation in the elderly. Pacemaker Selection in the Elderly (PASE) Investigators.

Pacemakers are frequently implanted, yet accurate prospective data on implant complications are limited. Elderly patients may be at increased risk of implant complications and are increasingly being referred for pacemaker implantation. The purpose of the present analysis was to define the incidence and possible predictors of serious complications of dual chamber permanent pacemaker implantation in the elderly. Therefore, we sought to prospectively identify the incidence and predictors of pacemaker implant complications in a large multicenter trial involving patients receiving a dual chamber pacemaker. The Pacemaker Selection in the Elderly (PASE) study was a prospective trial designed to evaluate quality of life in dual chamber pacemaker recipients age 65 years or older randomized to DDDR versus VVIR programming. In addition to being age 65 years or older, patients enrolled in this study were in normal sinus rhythm, and had standard indications for permanent pacemaker implantation. All patients received dual chamber pacemakers and were randomized to DDDR versus VVIR pacing. Pacemaker implant complications were collected on standardized forms which were completed at pacemaker implantation and during follow-up appointments. In this study of 407 patients, there were 26 complications occurring in 25 patients (6.1%). The most frequent complication was lead dislodgment which occurred in 9 patients. This was followed by pneumothorax (8 patients) and cardiac perforations (4 patients). In 18 patients (4.4%) repeat surgical procedures (including chest tubes) were required. Complications were noted prior to discharge in only 18 patients. There were no significant predictors of overall complications. Pneumothorax was more frequent in patients > or = 75 years old, and was observed only in patients with subclavian venous access. In conclusion, complications from pacemaker implantation in the elderly are seen in 6.1% of patients and 4.4% of patients require a repeat surgical procedure. Other than advanced age and lower weight predicting for pneumothorax, there are no significant clinical predictors of complications.

Increased prevalence of significant tricuspid regurgitation in patients with transvenous pacemakers leads.

Transvenous pacemaker leads are associated with an increased prevalence of tricuspid regurgitation. This hemodynamic derangement should be considered as part of the clinical cost and complications of permanent pacemaker implantation.

Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators.

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.

Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: The SAVE Study Experience. SAVE Investigators. Survival and Ventricular Enlargement.

BACKGROUND: As a result of randomized controlled trials with calcium channel blockers after myocardial infarction, concern has developed that these agents are associated with an increased risk of cardiovascular events, particularly in the presence of left ventricular dysfunction. METHODS: To test the hypothesis that calcium channel blockers increase cardiovascular events in such patients, the incidence of all-cause mortality, cardiovascular death, severe heart failure, and recurrent infarction was examined in 940 patients taking calcium channel blockers and 1180 not taking them 24 hours before randomization to placebo or captopril in the Survival and Ventricular Enlargement (SAVE) Trial. All patients had an ejection fraction < or =40%. Relative risks for calcium channel blocker users versus nonusers and the 95% confidence intervals were computed with univariate and multivariate Cox regressions. Adjustments were made for differences in baseline covariates. RESULTS: For all causes of mortality, the relative risk for calcium channel blocker users versus nonusers was 0.96, with the 95% confidence interval of 0.78 to 1.17. In the SAVE placebo and captopril groups, the relative risks for the development of severe heart failure among the calcium channel block users versus nonusers were 0.95 and 1.23, with the 95% confidence interval of 0.72 to 1.25 and 0.88 to 1.71, respectively. A similar neutral result held for patients with and without a history of hypertension. Furthermore, calcium channel blockers did not alter the benefit of the angiotensin converting enzyme inhibitor, captopril. CONCLUSIONS: This analysis of the nonrandomized clinical use of calcium channel blockers in the postmyocardial infarction population with left ventricular dysfunction did not identify either a clinical deterioration or improvement with respect to subsequent cardiovascular events.

[Interpretation of negative clinical trials]. / La interpretación de los ensayos clínicos negativos.

Randomized clinical trials without statistically significant differences between treatment groups may provide useful information for clinicians. However, negative trials must be interpreted cautiously, since the absence of evidence of treatment effect is not the same as evidence of absence of treatment effect. Before the reader of a negative article can conclude that one intervention was not better than the other, the potential causes of a negative study should be explored. The objective of this manuscript is to critically describe some of the most common methodological problems that can explain the lack of difference between studied groups in randomized clinical trials.

Clinical significance of mitral regurgitation after acute myocardial infarction. Survival and Ventricular Enlargement Investigators.

BACKGROUND: Mitral regurgitation (MR) may complicate acute myocardial infarction (MI). However, it is not known whether mild MR is an independent predictor of post-MI outcome. METHODS AND RESULTS: The study cohort consisted of 727 Survival and Ventricular Enlargement Study patients who underwent cardiac catheterization, including left ventriculography, up to 16 days after MI. Left ventriculograms were analyzed for diastolic and systolic volumes, global left ventricular sphericity, extent of wall motion abnormality, and endocardial curvature. The presence of MR was related to the risk of developing a cardiovascular event during 3.5 years of follow-up. MR was present in 141 patients (19.4%). Severe (3+) MR was present in only 2 patients. Patients with MR were more likely to have a persistently occluded infarct artery (MR versus no MR, 27.3% versus 15.2%; P=.001). Although the ejection fractions were similar, MR patients had larger end-systolic and end-diastolic volumes and more spherical ventricles than patients without MR. Sphericity change from diastole to systole was also significantly reduced in MR patients. Patients with MR were more likely to experience cardiovascular mortality (29% versus 12%; P<.001), severe heart failure (24% versus 16%; P=.0153), and the combined end point of cardiovascular mortality, severe heart failure, or recurrent myocardial infarction (47% versus 29%; P<.001). The presence of MR was an independent predictor of cardiovascular mortality (relative risk, 2.00; 95% CI, 1.28 to 3.04). CONCLUSIONS: Mild MR is an independent predictor of post-MI mortality. As such, it adds important information for risk stratification of post-MI patients.

Ventricular dysfunction and the risk of stroke after myocardial infarction.

BACKGROUND: In patients who have had a myocardial infarction, the long-term risk of stroke and its relation to the extent of left ventricular dysfunction have not been determined. We studied whether a reduced left ventricular ejection fraction is associated with an increased risk of stroke after myocardial infarction and whether other factors such as older age and therapy with anticoagulants, thrombolytic agents, or captopril affect long-term rates of stroke. METHODS: We performed an observational analysis of prospectively collected data on 2231 patients who had left ventricular dysfunction after acute myocardial infarction who were enrolled in the Survival and Ventricular Enlargement trial. The mean follow-up was 42 months. Risk factors for stroke were assessed by both univariate and multivariate Cox proportional-hazards analysis. RESULTS: Among these patients, 103 (4.6 percent) had fatal or nonfatal strokes during the study (rate of stroke per year of follow-up, 1.5 percent). The estimated five-year rate of stroke in all the patients was 8.1 percent. As compared with patients without stroke, patients with stroke were older (mean [+/-SD] age, 63+/-9 years vs. 59+/-11 years; P<0.001) and had lower ejection fractions (29+/-7 percent vs. 31+/-7 percent, P=0.01). Independent risk factors for stroke included a lower ejection fraction (for every decrease of 5 percentage points in the ejection fraction there was an 18 percent increase in the risk of stroke), older age, and the absence of aspirin or anticoagulant therapy. Patients with ejection fractions of < or = 28 percent after myocardial infarction had a relative risk of stroke of 1.86, as compared with patients with ejection fractions of more than 35 percent (P=0.01). The use of thrombolytic agents and captopril had no significant effect on the risk of stroke. CONCLUSIONS: During the five years after myocardial infarction, patients have a substantial risk of stroke. A decreased ejection fraction and older age are both independent predictors of an increased risk of stroke. Anticoagulant therapy appears to have a protective effect against stroke after myocardial infarction.