Prognosis of patients with left ventricular diastolic pressure abnormality: a long-term survival study in patients without coronary artery disease.

BACKGROUND: Given that an elevated left ventricular (LV) end-diastolic pressure reflects an abnormality of diastolic function, we analyzed the outcome of this finding in patients without coronary artery disease (CAD). HYPOTHESIS: The degree to which diastolic dysfunction influences mortality has been confounded in most studies by CAD and advanced age. METHODS: We performed a retrospective study of 876 patients with normal coronary arteries on arteriography. Of these, 115 patients had a left ventricular end-diastolic pressure of > or = 15 mmHg with an ejection fraction (EF) > or = 50%. We compared the mortality in this group (Group A) with the reported outcome in the general population, adjusted for age, gender, and race, as well as the mortality of a group of patients from the same cohort (Group B) with both diastolic and systolic dysfunction (n = 60), defined as a LVEF < 50%. RESULTS: Follow-up was for a mean of 63 months. In Group A, all-cause mortality was 5% (six patients); two deaths were from cardiac causes. The mean annual mortality in this group (1.2%) was similar to the adjusted annual mortality of the general population (1.1%), and it was significantly lower than the annual mortality (6%) in Group B (p < 0.03). CONCLUSIONS: Our study results indicate that diastolic dysfunction with a normal EF, in the absence of CAD and systolic dysfunction, has an excellent prognosis over a long period (5-6 years).

Electrocardiographic diagnosis of left ventricular hypertrophy: the effect of left ventricular wall thickness, size, and mass on the specific criteria for left ventricular hypertrophy.

BACKGROUND: The purpose of our study was to determine the relative importance and effect of an increased left ventricle wall thickness, left ventricular diastolic diameter, and left ventricular mass (LVM) on the performance of the 4 major electrocardiogram (ECG) criteria of left ventricular hypertrophy (LVH) and to determine how these findings could be incorporated into the routine ECG interpretation of LVH. METHODS: The ECG criteria of LVH that we chose to examine were voltage, repolarization abnormalities, left atrial abnormality, and ventricular conduction time. We analyzed data from 608 consecutive patients with left ventricular wall thickness of >13 mm on the echocardiogram and with a concurrent ECG. We arbitrarily divided patients into 3 groups (groups I-III) according to the calculated LVM. Group I had an LVM of <400 g; group II had an LVM from 400 to 600 g, and group III had an LVM of >600 g. We evaluated the effect of increasing LVM, wall thickness, and ventricular diameter on the performance of the 4 ECG criteria at different severity of thickness, diameter, and mass. RESULTS: An increase in the echocardiogram-derived LVM had significant effect on all 4 ECG criteria. As LVM progressively increased from groups I to III, the frequency of voltage criteria for LVH increased from 52% to 83%; left atrial abnormality rose from 46% to 68%; ST-T wave changes increases from 55% to 95%, and QRS prolongation significantly increased from 42% to 70%. CONCLUSION: Increased wall thickness and ventricular diameter failed to correlate with the overall ECG score or significantly influence the frequency of any of the 4 ECG criteria for LVH in patients when LVM was held relatively constant. We also demonstrated that an increasing number of criteria on the ECG are associated with a greater mean LVM.

Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction.

The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried < or =1, 20% for those with 2 to 4, and 13% for those with > or =5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.

Improving clinical practice guidelines for practicing cardiologists.

Cardiac-related clinical practice guidelines have become an integral part of the practice of cardiology. Unfortunately, these guidelines are often long, complex, and difficult for practicing cardiologists to use. Guidelines should be condensed and their format upgraded, so that the key messages are easier to comprehend and can be applied more readily by those involved in patient care. After presenting the historical background and describing the guideline structure, we make several recommendations to make clinical practice guidelines more user-friendly for clinical cardiologists. Our most important recommendations are that the clinical cardiology guidelines should focus exclusively on (1) class I recommendations with established benefits that are supported by randomized clinical trials and (2) class III recommendations for diagnostic or therapeutic approaches in which quality studies show no benefit or possible harm. Class II recommendations are not evidence based but reflect expert opinions related to published clinical studies, with potential for personal bias by members of the guideline committee. Class II recommendations should be published separately as "Expert Consensus Statements" or "Task Force Committee Opinions," so that both majority and minority expert opinions can be presented in a less dogmatic form than the way these recommendations currently appear in clinical practice guidelines.

Prognosis and response to therapy of first inpatient and outpatient heart failure event in a heart failure clinical trial: MADIT-CRT.

AIMS: Hospitalization for worsening heart failure (HF) is known to increase mortality and morbidity risk and has been frequently used as an endpoint in randomized clinical trials. Whether outpatient management of HF exacerbation carries similar prognostic and therapeutic information is less well known, but could be important for the design of trials that use HF hospitalization as an endpoint. METHODS AND RESULTS: MADIT-CRT randomized patients with mild HF symptoms to resynchronization therapy vs. control with an average follow-up of 3.3 years and a total of 191 deaths. HF events were centrally adjudicated for receiving i.v. decongestive therapy in an outpatient setting, or an augmented HF regimen during a hospital stay. Patients were compared according to whether their first HF was an out- or inpatient event. The first primary event was non-fatal outpatient HF, non-fatal inpatient HF, and death in 52, 331, and 78 patients, respectively. Patients with inpatient HF tended to be older and more likely to have HF of ischaemic aetiology than subjects who developed outpatient HF events. The risk of death following either type of non-fatal HF events was extremely high [hazard ratio (HR) 12.4, 95% confidence interval (CI) 9.1-16.9 for inpatient HF; HR 10.7, 95% CI 6.1-18.7 for outpatient HF] compared with subjects without non-fatal HF events. Allocation to CRT-D was associated with significant reduction in both types of HF. CONCLUSION: Outpatient management of worsening HF portends a high risk of death, similar to inpatient HF events, and may be equally sensitive to the effects of therapy. These findings suggest that outpatient HF events should be considered in publicly reported outcomes measures and future HF clinical trials. TRIAL REGISTRATION: NCT01294449.

Senior academic physicians and retirement considerations.

An increasing number of academic senior physicians are approaching their potential retirement in good health with accumulated clinical and research experience that can be a valuable asset to an academic institution. Considering the need to let the next generation ascend to leadership roles, when and how should a medical career be brought to a close? We explore the roles for academic medical faculty as they move into their senior years and approach various retirement options. The individual and institutional considerations require a frank dialogue among the interested parties to optimize the benefits while minimizing the risks for both. In the United States there is no fixed age for retirement as there is in Europe, but European physicians are initiating changes. What is certain is that careful planning, innovative thinking, and the incorporation of new patterns of medical practice are all part of this complex transition and timing of senior academic physicians into retirement.

Predictors of long-term mortality in Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) patients with implantable cardioverter-defibrillators.

BACKGROUND: Data on long-term follow-up and factors influencing mortality in implantable cardioverter-defibrillator (ICD) recipients are limited. OBJECTIVE: The aim of this study was to evaluate mortality during long-term follow-up and the predictive value of several risk markers in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) patients with implanted cardioverter-defibrillators (ICDs). METHODS: The study involved U.S. patients from the MADIT II trial randomized to and receiving ICD treatment. Data regarding long-term mortality were retrieved from the National Death Registry. Several clinical, biochemical, and electrocardiogram variables were tested in a multivariate Cox model for predicting long-term mortality, and a score identifying high-, medium-, and lower risk patients was developed. RESULTS: The study population consisted of 655 patients, mean age 64 +/- 10 years. During a follow-up of up to 9 years, averaging 63 months, 294 deaths occurred. The 6-year cumulative probability of death was 40%, with evidence of a constant risk of about 8.5% per year among survivors. Median survival was estimated at 8 years. Multivariate analysis identified age >65 years, New York Heart Association class 3-4, diabetes, non-sinus rhythm, and increased levels of blood urea nitrogen as independent risk predictors of mortality. Patients with three or more of these risk factors were characterized by a 6-year mortality rate of 68%, compared with 43% in those with one to two risk factors and 19% in patients with no risk factors. CONCLUSION: A combination of a few readily available clinical variables indicating advanced disease and comorbid conditions identifies ICD patients at high risk of mortality during long-term follow-up.