Nathan W. Brunner

Right Heart Score for Predicting Outcome in Idiopathic, Familial, or Drug- and Toxin- Associated Pulmonary Arterial Hypertension

OBJECTIVES This study sought to determine whether a simple score combining indexes of right ventricular (RV) function and right atrial (RA) size would offer good discrimination of outcome in patients with pulmonary arterial hypertension (PAH). BACKGROUND Identifying a simple score of outcome could simplify risk stratification of patients with PAH and potentially lead to improved tailored monitoring or therapy. METHODS We recruited patients from both Stanford University (derivation cohort) and VU University Medical Center (validation cohort). The composite endpoint for the study was death or lung transplantation. A Cox proportional hazard with bootstrap CI adjustment model was used to determine independent correlates of death or transplantation. A predictive score was developed using the beta coefficients of the multivariable models. RESULTS For the derivation cohort (n = 95), the majority of patients were female (79%), average age was 43 ± 11 years, mean pulmonary arterial pressure was 54 ± 14 mm Hg, and pulmonary vascular resistance index was 25 ± 12 Wood units × m(2). Over an average follow-up of 5 years, the composite endpoint occurred in 34 patients, including 26 deaths and 8 patients requiring lung transplant. On multivariable analysis, RV systolic dysfunction grade (hazard ratio [HR]: 3.4 per grade; 95% confidence interval [CI]: 2.0 to 7.8; p < 0.001), severe RA enlargement (HR: 3.0; 95% CI: 1.3 to 8.1; p = 0.009), and systemic blood pressure <110 mm Hg (HR: 3.3; 95% CI: 1.5 to 9.4; p < 0.001) were independently associated with outcome. A right heart (RH) score constructed on the basis of these 3 parameters compared favorably with the National Institutes of Health survival equation (0.88; 95% CI: 0.79 to 0.94 vs. 0.60; 95% CI: 0.49 to 0.71; p < 0.001) but was not statistically different than the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) score c-statistic of 0.80 (95% CI: 0.69 to 0.88) with p = 0.097. In the validation cohort (n = 87), the RH score remained the strongest independent correlate of outcome. CONCLUSIONS In patients with prevalent PAH, a simple RH score may offer good discrimination of long-term outcome.

Effectiveness of Statin Prescribing on Reducing Mortality in South Asian, Chinese, and White Patients With Diabetes

BACKGROUND Clinical trials have shown that 3-hydroxy-3-methylgutaryl coenzyme A reductase inhibitors (statins) reduce mortality in patients with diabetes. However, as these trials were conducted in largely white populations, it is unknown whether the benefits of statins can be extended to other ethnic populations in which the incidence of diabetes is rising sharply. We investigated associations between statin prescription and outcomes in a multiethnic population with diabetes. METHODS We identified all patients with newly diagnosed diabetes in British Columbia, Canada (1993-2006), using administrative data. Validated surname analysis was used to identify South Asian and Chinese patients. Statin prescribing was defined as any prescription filled within 1 year of diabetes diagnosis according to a provincial pharmacy database. Median length of follow-up was 4 years. Cox proportional hazards models were constructed for each ethnic group to determine the association of statin prescribing with time to death, adjusting for covariates including age, sex, socioeconomic status, and comorbid conditions. RESULTS There were 143,630 white, 9529 South Asian, and 14,084 Chinese persons with newly diagnosed diabetes. White patients were older and had more comorbidity than the other groups. Statin prescribing was associated with lower mortality compared with no prescribing within each ethnic group: South Asian (Hazard Ratio [HR], 0.69; 95% confidence interval [CI], 0.55-0.86; P = 0.001), Chinese (HR, 0.60; 95% CI, 0.49-0.72; P < 0.0001), and white (HR, 0.65; 95% CI, 0.63-0.67; P < 0.0001). CONCLUSIONS Statin prescribing is associated with lower mortality in white, Chinese, and South Asian patients with newly diagnosed diabetes, confirming the benefits of statins across these ethnic groups.

Perioperative pharmacological management of pulmonary hypertensive crisis during congenital heart surgery

Pulmonary hypertensive crisis is an important cause of morbidity and mortality in patients with pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD) who require cardiac surgery. At present, prevention and management of perioperative pulmonary hypertensive crisis is aimed at optimizing cardiopulmonary interactions by targeting prostacyclin, endothelin, and nitric oxide signaling pathways within the pulmonary circulation with various pharmacological agents. This review is aimed at familiarizing the practitioner with the current pharmacological treatment for dealing with perioperative pulmonary hypertensive crisis in PAH-CHD patients. Given the life-threatening complications associated with pulmonary hypertensive crisis, proper perioperative planning can help anticipate cardiopulmonary complications and optimize surgical outcomes in this patient population.

Prognostic utility of right atrial emptying fractions in pulmonary arterial hypertension.

Although left atrial function has been extensively studied in patients with heart failure, the determinants and clinical correlates of impaired right atrial (RA) function have been poorly studied. We investigated measures of RA function in pulmonary arterial hypertension (PAH). We identified all treatment-naive patients with World Health Organization category 1 PAH seen at our center during 2000–2011 who had right heart catheterization and 6-minute walk test (6MWT) within 1 month of initial echocardiographic examination. Atrial size was measured using the monoplane area-length method, and atrial function was quantified using total, passive, and active RA emptying fractions (RAEFs). We compared measures of RAEF with known prognostic clinical, echocardiographic, and hemodynamic parameters. For the subset of patients with follow-up echocardiographic examination/6MWT within 6–18 months, we investigated the change in RAEF. In an exploratory analysis, we investigated the association between RAEF and mortality. Our population consisted of 39 patients with treatment-naive (incident) PAH, 30 of whom had follow-up testing. The mean total, passive, and active RAEFs were 24.4% ± 15.1%, 8.5% ± 6.9%, and 17.6% ± 13.9%, respectively. Total and active RAEFs correlated with tricuspid annular plane systolic excursion (P = 0.004 and P = 0.005) and cardiac output (P = 0.02 and P = 0.01). The change in active RAEF correlated with change in 6-minute walk distance (P = 0.02). In our Cox regression analysis, low active and total RAEF were associated with mortality, with hazard ratios of 5.6 (95% confidence interval [CI], 1.2–26.2; P = 0.03) and 4.2 (95% CI, 1.1–15.5; P = 0.03), respectively. Passive RAEF was poorly reproducible and not associated with outcome. Measures of RAEF appear to have prognostic importance in PAH and warrant further study.

Outcomes of non-acute coronary syndrome patients discharged from the emergency department with troponin positivity

BACKGROUND Cardiac troponin elevation portends a worse prognosis in diverse patient populations. The significance of troponin elevation in patients discharged from emergency departments (EDs) without inpatient admission is not well known. METHODS Patients without a diagnosis of acute coronary syndrome discharged from two EDs between April 1, 2006, and December 31, 2007, with an abnormal cardiac troponin (troponin positive [TP]) were compared to a troponin-negative (TN) cohort matched for age, sex, and primary discharge diagnosis. Outcomes were obtained by linking with a regional ED and a provincial vital statistics database and adjusted for the following: estimated glomerular filtration rate, do-not-resuscitate status, history of coronary artery disease, Canadian Triage and Acuity Scale, and left ventricular hypertrophy on electrocardiography. The primary outcome was a composite of death or admission to hospital within 1 year. RESULTS Our total cohort (n  =  344) consisted of 172 TP and 172 TN patients. In the univariate analysis, TP patients had a higher rate of the primary outcome (OR 3.2, 95% CI 2.1-5.0, p < 0.001) and both of its components (p < 0.001). After adjusting for covariates, positive troponin remained an independent predictor of the primary outcome (OR 2.1, 95% CI 1.3-3.4, p  =  0.005) and inpatient admission (OR 2.0, 95% CI 1.2-3.4, p  =  0.006). There was no significant difference in death (OR 1.3, 95% CI 0.6-2.9, p  =  0.5) after adjustment. CONCLUSIONS A positive troponin assay during ED stay in discharged patients is an independent marker for risk of subsequent admission. Our findings suggest that the prognostic power of an abnormal troponin extends to patients discharged from the ED.

IMPROVEMENT IN RIGHT ATRIAL FUNCTION IS ASSOCIATED WITH IMPROVED FUNCTIONAL CAPACITY IN PULMONARY ARTERIAL HYPERTENSION

Patients with pulmonary arterial hypertension (PAH) develop progressive right atrial (RA) remodeling and reduced RA function. RA emptying fraction (RAEF) is a simple measure of RA function. The significance of temporal changes in RAEF have not been investigated in PAH. We identified patients with

RIGHT ATRIAL EMPTYING FRACTIONS ARE ASSOCIATED WITH SURVIVAL IN PULMONARY ARTERIAL HYPERTENSION

Parameters of left atrial function have prognostic importance in left-sided heart failure. Analogous parameters of right atrial function have been sparingly investigated right ventricular (RV) failure. We investigated associations between right atrial emptying fraction (RAEF) and survival in

The prognostic importance of the diastolic pulmonary gradient, transpulmonary gradient, and pulmonary vascular resistance in patients undergoing transcatheter aortic valve replacement

To evaluate the association between markers of precapillary pulmonary hypertension (PH) and survival in transcatheter aortic valve replacement (TAVR).

A case of recurrent pericardial constriction presenting with severe pulmonary hypertension.

Chronic constrictive pericarditis (CP) is a relatively rare condition in which the pericardium becomes fibrotic and noncompliant, eventually resulting in heart failure due to impaired ventricular filling. The only curative treatment is pericardiectomy. Classically, CP does not usually cause severe pulmonary hypertension. When attempting to differentiate CP from restrictive cardiomyopathy, the presence of severely elevated pulmonary arterial pressure is used as a diagnostic criterion ruling against CP. We present a case of proven recurrent pericardial constriction following pericardiectomy presenting with severe pulmonary hypertension.

Validity of algorithm for estimating left sided filling pressures on echocardiography in a population referred for pulmonary arterial hypertension

The determination of LV filling pressure is integral to the diagnosis of pulmonary arterial hypertension (PAH). The American Society of Echocardiography (ASE) has devised algorithms for their estimation. We aimed to test these algorithms in a population referred for suspected PAH. In our retrospective study, we evaluated the accuracy of the ASE Algorithms compared to right heart catheterization done within three months, in patients seen during 2006–2014. All echocardiograms were classified as showing normal, elevated or indeterminate filling pressures. Those with indeterminate pressures were excluded. We evaluated the diagnostic properties of this algorithm to predict a pulmonary artery wedge pressure (PAWP) and left ventricular end diastolic pressure (LVEDP) >15 mmHg. A total of 94 patients were included. The ASE algorithms yielded indeterminate results in 50 (53.2%) patients. This occurred more commonly in older patients and patients with cardiovascular comorbidities. The algorithm had a high sensitivity for predicting an elevated PAWP at 89.5% (95% confidence interval [CI] = 66.9–98.7) and an elevated LVEDP at 100% (95% CI = 76.8–100). The algorithm had a negative predictive value of 81.8% and 100% for predicting an elevated PAWP (95% CI = 52.4–94.8) and LVEDP, respectively, but a poor positive predictive value. The ASE algorithm for predicting LV filling pressures often cannot be applied in populations with suspected PAH. When they are interpretable, they have a high negative predictive value for elevated PAWP and LVEDP. We recommend caution when using these algorithms in populations with suspected PAH.