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There are multiple proposed mechanisms for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). We hypothesized that coronary microvascular dysfunction is common in these patients. In a prospective, observational study, patients undergoing cardiac catheterization with HFpEF [left ventricular (LV) ejection fraction ≥ 50% and with clinical HF] were compared with similar patients without HFpEF. Patients with ≥50% stenosis were excluded, and coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were measured after adenosine administration using a guidewire, with CFR ≤ 2 and IMR ≥ 23 being abnormal. Baseline characteristics and CFR and IMR were compared in 30 HFpEF patients and 14 control subjects. Compared with control subjects, HFpEF patients were older (65.4 ± 9.6 vs. 55.1 ± 3.1 yr, P < 0.01), had higher numbers of comorbidities (4.4 ± 1.5 vs. 2.6 ± 1.9, P = 0.002), had higher median B-type natriuretic peptide [161 (interquartile range: 75-511) pg/dl vs. 37 (interquartile range: 18.5-111) pg/dl, P < 0.01], and had higher LV end-diastolic pressure (17.8 ± 4.2 vs. 8.4 ± 4.2, P < 0.01). HFpEF patients had lower CFR (2.55 ± 1.60 vs. 3.84 ± 1.89, P = 0.024) and higher IMR (26.7 ± 10.3 vs. 19.7 ± 9.7 units, P = 0.037) than control subjects. Most (71.4%) control subjects had normal coronary physiology, whereas 36.7% of HFpEF patients had both abnormal CFR and IMR and another 36.7% had either abnormal CFR or IMR. In conclusion, this is the first study that has reported invasively determined CFR and IMR in HFpEF patients. We demonstrated the presence of four distinct coronary physiology groups in HFpEF patients. Investigation into the potential mechanisms for these findings is needed. NEW & NOTEWORTHY In this prospective observational study of patients with heart failure with preserved ejection fraction (HFpEF), we found that patients with HFpEF had more abnormalities of coronary flow and resistance than asymptomatic control patients, indicating that coronary microvascular dysfunction may play a role in the HFpEF disease process.

Chronotropic incompetence (CI) is common in heart failure with preserved ejection fraction (HFpEF) and may be a key reason underlying exercise intolerance in these patients. However, the determinants of CI in HFpEF are unknown. We prospectively studied 157 patients with consecutive HFpEF who underwent cardiopulmonary exercise testing and defined CI according to specific thresholds of the percent heart rate reserve (%HRR). CI was diagnosed as present if %HRR <80 if not taking a β blocker and <62 if taking β blockers. Participants who achieved inadequate exercise effort (respiratory exchange ratio ≤1.05) on cardiopulmonary exercise testing were excluded. Multivariable-adjusted logistic regression was used to determine the factors associated with CI. Of the 157 participants, 108 (69%) achieved a respiratory exchange ratio >1.05 and were included in the final analysis. Of these 108 participants, 70% were women, 62% were taking β blockers, and 38% had chronic kidney disease. Most patients with HFpEF met criteria for CI (81 of 108; 75%). Lower estimated glomerular filtration rate (GFR), higher B-type natriuretic peptide, and higher pulmonary artery systolic pressure were each associated with CI. A 1-SD decrease in GFR was independently associated with CI after multivariable adjustment (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4, p = 0.02). The association between reduced GFR and CI persisted when considering a variety of measures of chronotropic response. In conclusion, reduced GFR is the major clinical correlate of CI in patients with HFpEF, and further study of the relation between chronic kidney disease and CI may provide insight into the pathophysiology of CI in HFpEF., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Electromechanical coupling, a well-described phenomenon in systolic dysfunction, has not been well studied in diastole. We hypothesized that the ECG T-peak to T-end (TpTe) interval, representing transmural dispersion of repolarization, is associated with echocardiographic markers of diastolic dysfunction (DD)., Methods and Results: We performed a prospective, cross-sectional study of the association between TpTe and markers of DD in 84 consecutive, unselected patients referred for exercise echocardiography. We systematically measured TpTe on the resting ECG, and we performed comprehensive assessment of DD at rest and at peak stress. ECGs and echocardiograms were analyzed independently, blinded to each other and to all clinical data. By univariable analysis, increased TpTe was associated with older age, increased E/e' ratio, and DD (P<0.05 for all associations after correcting for multiple comparisons). Increased TpTe was inversely associated with reduced tissue Doppler e' velocity, a marker of DD (R=-0.66, P<0.0001). This association persisted after adjusting for age, QTc, exercise-induced wall motion abnormalities, and left ventricular mass index (β=-0.41 [95% confidence interval, -0.70 to -0.12] cm/s per 10-ms increase in TpTe; P=0.006). Baseline TpTe was also independently associated with resting DD (adjusted odds ratio, 3.9 [95% confidence interval, 1.4-10.7]; P=0.009) and peak exercise E/e' ratio (P<0.0001)., Conclusions: Increased TpTe is associated with both resting and exercise-induced DD. Electromechanical coupling may represent a pathophysiologic link between electrical transmural dispersion of repolarization and abnormal myocardial relaxation, and may be a novel therapeutic target.