David R. Thiemann

Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance Heralds an Adverse Prognosis in Nonischemic Cardiomyopathy

OBJECTIVES We examined whether the presence and extent of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) predict adverse outcomes in nonischemic cardiomyopathy (NICM) patients. BACKGROUND Morbidity and mortality is high in NICM patients. However, the clinical course of an individual patient is unpredictable and current risk stratification approaches are limited. Cardiovascular magnetic resonance detects myocardial fibrosis, which appears as LGE after contrast administration and may convey prognostic importance. METHODS In a prospective cohort study, 65 NICM patients with left ventricular (LV) ejection fraction < or =35% underwent CMR before placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death. The CMR images were analyzed for the presence and extent of LGE and for LV function, volumes, and mass. Patients were followed for an index composite end point of 3 cardiac events: hospitalization for heart failure, appropriate ICD firing, and cardiac death. RESULTS A total of 42% (n = 27) of patients had CMR LGE, averaging 10 +/- 13% of LV mass. During a 17-month median follow-up, 44% (n = 12) of patients with LGE had an index composite outcome event versus only 8% (n = 3) of those without LGE (p < 0.001 for Kaplan-Meier survival curves). After adjustment for LV volume index and functional class, patients with LGE had an 8-fold higher risk of experiencing the primary outcome (hazard ratio 8.2, 95% confidence interval 2.2 to 30.9; p = 0.002). CONCLUSIONS A CMR LGE in NICM patients strongly predicts adverse cardiac outcomes. The CMR LGE may represent the end-organ consequences of sustained adrenergic activation and adverse LV remodeling, and its identification may significantly improve risk stratification strategies in this high risk population. (Imaging Techniques for Identifying Factors of Sudden Cardiac Death Risk; NCT00181233).

The association between hospital volume and survival after acute myocardial infarction in elderly patients.

Background Patients with chest pain thought to be due to acute coronary ischemia are typically taken by ambulance to the nearest hospital. The potential benefit of field triage directly to a hospital that treats a large number of patients with myocardial infarction is unknown. Methods We conducted a retrospective cohort study of the relation between the number of Medicare patients with myocardial infarction that each hospital in the study treated (hospital volume) and long-term survival among 98,898 Medicare patients 65 years of age or older. We used proportional-hazards methods to adjust for clinical, demographic, and health-system–related variables, including the availability of invasive procedures, the specialty of the attending physician, and the area of residence of the patient (rural, urban, or metropolitan). Results The patients in the quartile admitted to hospitals with the lowest volume were 17 percent more likely to die within 30 days after admission than patients in the quartile admitted to hos...

A randomized trial of the efficacy of multidisciplinary care in heart failure outpatients at high risk of hospital readmission

OBJECTIVES We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period. BACKGROUND Hospital admission for CHF is an important problem amenable to improved outpatient management. METHODS Two hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patients primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patients primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis. RESULTS The median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups. CONCLUSIONS This study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF.

Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years.

BACKGROUND The benefit of intravenous thrombolytic therapy in elderly patients with myocardial infarction is uncertain. There are no randomized trials of thrombolytic efficacy or observational studies of clinical effectiveness that focus specifically on the elderly. METHODS AND RESULTS To determine whether thrombolytic therapy for elderly patients is associated with a survival advantage in a large observational database, we conducted a retrospective cohort study of 7864 Medicare fee-for-service patients aged 65 to 86 years with the primary discharge diagnosis of acute myocardial infarction who were admitted with clinical and ECG indications for thrombolytic therapy and no absolute contraindications. The study included all US acute care nongovernment hospitals without on-site angioplasty capability. Using proportional-hazards methods, we found that in a comprehensive multivariate model, there was a significant interaction (P<0.001) between age and the effect of thrombolytic therapy on 30-day mortality rates. For patients 65 to 75 years old, thrombolytic therapy was associated with a survival benefit, consistent with randomized trials. Among patients aged 76 to 86 years, thrombolytic therapy was associated with a survival disadvantage, with a 30-day mortality hazard ratio of 1.38 (95% CI 1. 12 to 1.71, P=0.003). For these patients, there was no benefit from thrombolytic therapy in any clinical subgroup. CONCLUSIONS In nationwide clinical practice, thrombolytic therapy for patients >75 years old is unlikely to confer survival benefit and may have a significant survival disadvantage. Reperfusion research that is focused on elderly patients is urgently needed.

Pulmonary Capillary Wedge Pressure Augments Right Ventricular Pulsatile Loading

Background— Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (RPA) and compliance (CPA) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load. Methods and Results— Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the RPA-CPA relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent RPA-CPA hyperbolic (inverse) dependence, CPA=0.564/(0.047+RPA), with a near-constant resistance-compliance product (0.48±0.17 seconds). In the same patients, the systemic resistance-compliance product was highly variable. Severe pulmonary fibrosis (n=89) did not change the RPA-CPA relation. Increasing patient age led to a very small but statistically significant change in the relation. However, elevation of the pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly lowering CPA for any RPA and negatively correlating with the resistance-compliance product (P<0.0001). Conclusions— Pulmonary hypertension and pulmonary fibrosis do not significantly change the hyperbolic dependence between RPA and CPA, and patient age has only minimal effects. This fixed relationship helps explain the difficulty of reducing total right ventricular afterload by therapies that have a modest impact on mean RPA. Higher pulmonary capillary wedge pressure appears to enhance net right ventricular afterload by elevating pulsatile, relative to resistive, load and may contribute to right ventricular dysfunction.

PDE5A Inhibitor Treatment of Persistent Pulmonary Hypertension After Mechanical Circulatory Support

Background—Pulmonary hypertension (PH) secondary to left heart failure portends a poor prognosis and is a relative contraindication to heart transplantation at many centers. We tested the hypothesis that when PH persists after adequate left ventricle unloading via recent left ventricular assist device (LVAD) therapy, phosphodiesterase type 5A inhibition would decrease PH in this population. Methods and Results—We performed an open-label clinical trial using control patients not receiving therapy. Between 1999 and 2007, 138 consecutive patients undergoing cardiac transplantation evaluation with advanced left ventricular dysfunction, an elevated pulmonary capillary wedge pressure, and PH (defined by a pulmonary vascular resistance (PVR) >3 Woods Units), were treated with LVAD therapy. Fifty-eight of these patients reduced their pulmonary capillary wedge pressure to a value <15 mm Hg (11.8±2.0 mm Hg from baseline 23.2±6.2 mm Hg) 1 to 2 weeks after LVAD implantation, but despite this improvement, the PVR of these patients was only minimally affected (5.65±3.00 to 5.39±1.78 Wood Units). Twenty-six consecutive patients from this group with persistently elevated PVR were started on oral phosphodiesterase type 5A inhibition with sildenafil and titrated to an average of dose of 51.9 mg by mouth 3 times per day. The average PVR in the sildenafil-treated group fell from 5.87±1.93 to 2.96±0.92 Wood Units (P<0.001) and the mean pulmonary artery pressure fell from 36.5±8.6 to 24.3±3.6 mm Hg (P<0.0001) and was significantly lower when compared with the 32 LVAD recipients not receiving sildenafil at weeks 12 to 15 after the initial post-LVAD hemodynamic measurements (13 to 17 weeks post-LVAD implantation). In addition, hemodynamic measurements of right ventricular function in sildenafil-treated patients was also improved compared with patients not receiving sildenafil. Conclusions—In patients with persistent PH after recent LVAD placement, phosphodiesterase type 5A inhibition in this open-label trial resulted in a significant decrease in PVR when compared with control patients.

Effects of acute hormone therapy on recurrent ischemia in postmenopausal women with unstable angina

OBJECTIVES We tested whether acute hormone therapy reduces ambulatory electrocardiographic ischemia in postmenopausal (PMP) women with unstable angina (UA). BACKGROUND Endothelial dysfunction contributes to the pathophysiology of UA. Acute estrogen administration improves endothelial function in PMP women with coronary artery disease and increases coronary artery blood flow. METHODS Two hundred ninety-three PMP women with UA (mean age 69.7 years), treated with standard anti-ischemic therapy, were enrolled within 24 h of symptom onset. In a double-blind fashion, subjects were randomized to receive intravenous followed by oral conjugated estrogen for 21 days, intravenous estrogen followed by oral conjugated estrogen plus medroxyprogesterone for 21 days or placebo. The primary end point was the number of ambulatory electrocardiographic ischemic events over the first 48 h. Clinical events were also determined over six months of follow-up. RESULTS Electrocardiographic ischemia did not differ among the three randomized groups. The mean number of ischemic events per patient over 48 h was 0.74 for estrogen, 0.86 for estrogen plus progesterone and 0.74 for the placebo groups (p = 0.87). The percentage of patients with ischemic events and the mean duration of ischemia did not differ between hormone- and placebo-treated patients. In-hospital and six-month rates of adverse clinical events were also similar among the three randomized groups. CONCLUSIONS Acute hormone therapy does not reduce ischemia in PMP women with UA when added to standard anti-ischemic therapy.

Pulmonary artery measurements in pulmonary hypertension: the role of computed tomography.

Purpose: We studied the relationship between pulmonary artery diameter (PAD) as measured on computed tomography (CT) and pulmonary artery pressure (PAP) with the specific goal of assessing the reliability of various measurements on high-resolution chest CT as predictors of pulmonary hypertension (PH). Materials and Methods: In a preliminary study we determined the method of measuring the main PAD (mPAD) that best correlated with PAP. Using this approach we measured mPAD on CT and correlated the data with PAP obtained from right heart catheterization in 298 patients with known PH and in 102 controls. Various metrics were analyzed for their specificity and sensitivity as screening measurements for PH. Results: The mean PAD and mPAD/ascending aorta diameter (AAD) ratio were found to have the highest correlation with PAP (r=0.51 and 0.53, respectively; P<0.001). A threshold of mPAD>29.5 mm was found to be 70.8% sensitive and 79.4% specific for PH, and an mPAD threshold >31.5 mm had a sensitivity and specificity of 52.0% and 90.2%, respectively. An mPAD/AAD ratio >1 was found to be 70.8% sensitive and 76.5% specific for PH. There was no significant correlation between mPAD and body surface area or age (r=0.04 and 0.07, respectively). A strong statistically significant difference (P<0.0001) was found between mPAD and mPAD/AAD ratio between controls and the PH group. Conclusion: mPAD and mPAD/AAD ratio may be used to detect PH in patients of any age or with any body surface area.

Usefulness of Transesophageal Echocardiography in Predicting Mortality and Morbidity in Stroke Patients Without Clinically Known Cardiac Sources of Embolus

This study tested the hypothesis that stroke patients without a cardiac source of embolism suspected by clinical examination can be risk stratified by transesophageal echocardiography. Forty ischemic stroke patients without atrial fibrillation, prosthetic valves, ejection fraction < 20%, or recent myocardial infarction underwent multiplane transesophageal echocardiography: 24 (designated high risk) had > or = 1 of the following: left heart thrombus, vegetation, mass or spontaneous echo contrast, mobile ascending aortic or arch debris, patent foramen ovale, atrial septal defect or aneurysm, mitral annular calcification, mitral valve thickening, prolapse or mitral valve strands. End points were death, recurrent stroke, transient ischemic attack, myocardial infarction or peripheral embolism. Thirty-eight patients (95%) (23 high, 15 low risk) were followed for 14 +/- 8 months: 9 (24%) died of vascular causes including 4 who had a cardiac cause of death and 5 who had fatal strokes. Eight had recurrent strokes (4 nonfatal) and 1 nonfatal myocardial infarction occurred. Cardiovascular survival was predicted by transesophageal echocardiography: survival rates were 92% (low risk) and 63% (high risk) at 24 months (p = 0.036). Left atrial enlargement was independently associated with death from stroke (fatal stroke occurred in 25% of those with atrial enlargement compared to 8% of those with normal atrial dimension, p < or = 0.03), as was left atrial spontaneous echo contrast (50% died vs 9% without contrast, p < or = 0.03). Left ventricular hypertrophy and aortic atherosclerosis were both associated with the risk of recurrent stroke (30% of patients with ventricular hypertrophy had recurrent stroke compared to 10% with normal wall thickness (p < or = 0.05); 30% with aortic atherosclerosis had a recurrent stroke compared to none with a normal aorta (p < or = 0.05). Thus, transesophageal echocardiography clearly identifies patients at a high risk for cardiovascular mortality and morbidity after stroke despite an unsuspected source of embolism by clinical examination.

Measuring Clinical Information Technology in the ICU Setting: Application in a Quality Improvement Collaborative

OBJECTIVE Few instruments are available to measure the performance of intensive care unit (ICU) clinical information systems. Our objectives were: 1) to develop a survey-based metric that assesses the automation and usability of an ICUs clinical information system; 2) to determine whether higher scores on this instrument correlate with improved outcomes in a multi-institution quality improvement collaborative. DESIGN This is a cross-sectional study of the medical directors of 19 Michigan ICUs participating in a state-wide quality improvement collaborative designed to reduce the rate of catheter-related blood stream infections (CRBSI). Respondents completed a survey assessing their ICUs information systems. MEASUREMENTS The mean of 54 summed items on this instrument yields the clinical information technology (CIT) index, a global measure of the ICUs information system performance on a 100 point scale. The dependent variable in this study was the rate of CRBSI after the implementation of several evidence-based recommendations. A multivariable linear regression analysis was used to examine the relationship between the CIT score and the post-intervention CRBSI rates after adjustment for the pre-intervention rate. RESULTS In this cross-sectional analysis, we found that a 10 point increase in the CIT score is associated with 4.6 fewer catheter related infections per 1,000 central line days for ICUs who participate in the quality improvement intervention for 1 year (95% CI: 1.0 to 8.0). CONCLUSIONS This study presents a new instrument to examine ICU information system effectiveness. The results suggest that the presence of more sophisticated information systems was associated with greater reductions in the bloodstream infection rate.