The role of resting myocardial blood flow and myocardial blood flow reserve as a predictor of major adverse cardiovascular outcomes.

Cardiac perfusion PET is increasingly used to assess ischemia and cardiovascular risk and can also provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values. These have been shown to be prognostic biomarkers of adverse outcomes, yet MBF and MBFR quantification remains underutilized in clinical settings. We compare MBFR to traditional cardiovascular risk factors in a large and diverse clinical population (60% African-American, 35.3% Caucasian) to rank its relative contribution to cardiovascular outcomes. Major adverse cardiovascular events (MACE), including unstable angina, non-ST and ST-elevation myocardial infarction, stroke, and death, were assessed for consecutive patients who underwent rest-dipyridamole stress 82Rb PET cardiac imaging from 2012-2015 at the Hospital of the University of Pennsylvania (n = 1283, mean follow-up 2.3 years). Resting MBF (1.1 ± 0.4 ml/min/g) was associated with adverse cardiovascular outcomes. MBFR (2.1 ± 0.8) was independently and inversely associated with MACE. Furthermore, MBFR was more strongly associated with MACE than both traditional cardiovascular risk factors and the presence of perfusion defects in regression analysis. Decision tree analysis identified MBFR as superior to established cardiovascular risk factors in predicting outcomes. Incorporating resting MBF and MBFR in CAD assessment may improve clinical decision making.

Evaluation of Flow After Transcatheter Aortic Valve Replacement in Patients With Low-Flow Aortic Stenosis: A Secondary Analysis of the PARTNER Randomized Clinical Trial.

IMPORTANCE: Low-flow (LF) severe aortic stenosis (AS) is an independent predictor of mortality in patients undergoing aortic valve replacement (AVR). Little is known about improvement in flow after AVR and its effects on survival. OBJECTIVE: To determine whether higher flow (left-ventricular stroke volume index [LVSVI]) after transcatheter AVR (TAVR) would indicate better clinical outcomes in this at-risk population. DESIGN, SETTING, AND PARTICIPANTS: A substudy analysis of data from the Placement of Aortic Transcatheter Valves (PARTNER) randomized clinical trial and continued-access registry was conducted. A total of 984 participants with evaluable echocardiograms and baseline LF AS (LVSVI ≤35 mL/m2) were included. The trial was conducted at 26 sites in the United States and Canada. Patients were stratified after TAVR into tertiles by discharge LVSVI status (severe low flow [SLF], moderate low flow [MLF], and normal flow [(NF]). The present study was conducted from May 11, 2007, to January 9, 2012, with data analysis performed from April 25, 2014, to January 21, 2016. MAIN OUTCOMES AND MEASURES: The primary end point was all-cause mortality at 1 year. RESULTS: Baseline characteristics of 984 patients with LF AS included mean (SD) age, 84 (7) years; 582 (59.1%) men; mean Society of Thoracic Surgeons (STS) score, 11.4% (4.0%); and mean LVSVI, 27.6 (5.0) mL/m2. The discharge LVSVI values by group were SLF, 23.1 (3.5) mL/m2; MLF, 31.7 (2.2) mL/m2; and NF, 43.1 (7.0). All-cause mortality at 1 year was SLF, 26.5%; MLF, 20.1%; and NF, 19.6% (P = .045). Mean LVSVI normalized by 6 months in the MLF (35.9 [9.3] mL/m2) and NF (38.8 [11.1] mL/m2) groups, but remained low in the SLF group at 6 months and 1 year (31.4 [8.4] and 33.0 [8.3] mL/m2], respectively) (P < .001 for all groups). Reported as multivariate hazard ratio, mortality at 1 year was higher in the SLF group compared with the other groups (1.61; 95% CI, 1.17-2.23; P = .004). In addition to SLF, sex (1.59; 95% CI, 1.18-2.13; P = .002), presence of atrial fibrillation (1.41; 95% CI, 1.06-1.87; P = .02), STS score (1.03; 95% CI, 1.01-1.06; P = .02), presence of moderate or severe mitral regurgitation at discharge (1.65; 95% CI, 1.21-2.26; P = .001), pre-TAVR mean transvalvular gradient (0.98; 95% CI, 0.97-0.99; P = .004), and effective orifice area index (1.87; 95% CI, 1.09-3.19; P = .02) were independent predictors of 1-year mortality. CONCLUSIONS AND RELEVANCE: Severe LF at discharge is associated with an increased risk of mortality following TAVR in patients with severe AS and preexisting LF. The identification of remedial causes of persistent LF after TAVR may represent an opportunity to improve the outcome of these patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00530894.

Prevalence, clinical phenotype, and outcomes associated with normal B-type natriuretic peptide levels in heart failure with preserved ejection fraction.

B-type natriuretic peptide (BNP) is used widely to exclude heart failure (HF) in patients with dyspnea. However, most studies of BNP have focused on diagnosing HF with reduced ejection fraction (EF). The aim of this study was to test the hypothesis that a normal BNP level (≤100 pg/ml) is relatively common in HF with preserved EF (HFpEF), a heterogenous disorder commonly associated with obesity. A total of 159 consecutive patients enrolled in the Northwestern University HFpEF Program were prospectively studied. All subjects had symptomatic HF with EF >50% and elevated pulmonary capillary wedge pressure. BNP was tested at baseline in all subjects. Clinical characteristics, echocardiographic parameters, invasive hemodynamics, and outcomes were compared among patients with HFpEF with normal (≤100 pg/ml) versus elevated (>100 pg/ml) BNP. Of the 159 patients with HFpEF, 46 (29%) had BNP ≤100 pg/ml. Subjects with normal BNP were younger, were more often women, had higher rates of obesity and higher body mass index, and less commonly had chronic kidney disease and atrial fibrillation. EFs and pulmonary capillary wedge pressures were similar in the normal and elevated BNP groups (62 ± 7% vs 61 ± 7%, p = 0.67, and 25 ± 8 vs 27 ± 9 mm Hg, p = 0.42, respectively). Elevated BNP was associated with enlarged left atrial volume, worse diastolic function, abnormal right ventricular structure and function, and worse outcomes (e.g., adjusted hazard ratio for HF hospitalization 4.0, 95% confidence interval 1.6 to 9.7, p = 0.003). In conclusion, normal BNP levels were present in 29% of symptomatic outpatients with HFpEF who had elevated pulmonary capillary wedge pressures, and although BNP is useful as a prognostic marker in HFpEF, normal BNP does not exclude the outpatient diagnosis of HFpEF.