Win, Sithu

Importance Reduced heart rate during exercise is common and associated with impaired aerobic capacity in heart failure with preserved ejection fraction (HFpEF), but it remains unknown if restoring exertional heart rate through atrial pacing would be beneficial. Objective To determine if implanting and programming a pacemaker for rate-adaptive atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence. Design, Setting, and Participants Single-center, double-blind, randomized, crossover trial testing the effects of rate-adaptive atrial pacing in patients with symptomatic HFpEF and chronotropic incompetence at a tertiary referral center (Mayo Clinic) in Rochester, Minnesota. Patients were recruited between 2014 and 2022 with 16-week follow-up (last date of follow-up, May 9, 2022). Cardiac output during exercise was measured by the acetylene rebreathe technique. Interventions A total of 32 patients were recruited; of these, 29 underwent pacemaker implantation and were randomized to atrial rate responsive pacing or no pacing first for 4 weeks, followed by a 4-week washout period and then crossover for an additional 4 weeks. Main Outcomes and Measures The primary end point was oxygen consumption (V̇ o 2 ) at anaerobic threshold (V̇ o 2,AT ); secondary end points were peak V̇ o 2 , ventilatory efficiency (V̇ e /V̇ co 2 slope), patient-reported health status by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Results Of the 29 patients randomized, the mean age was 66 years (SD, 9.7) and 13 (45%) were women. In the absence of pacing, peak V̇ o 2 and V̇ o 2 at anaerobic threshold (V̇ o 2,AT ) were both correlated with peak exercise heart rate ( r = 0.46-0.51, P < .02 for both). Pacing increased heart rate during low-level and peak exercise (16/min [95% CI, 10 to 23], P < .001; 14/min [95% CI, 7 to 21], P < .001), but there was no significant change in V̇ o 2,AT (pacing off, 10.4 [SD, 2.9] mL/kg/min; pacing on, 10.7 [SD, 2.6] mL/kg/min; absolute difference, 0.3 [95% CI, −0.5 to 1.0] mL/kg/min; P = .46), peak V̇ o 2 , minute ventilation (V̇ e) /carbon dioxide production (V̇ co 2 ) slope, KCCQ-OSS, or NT-proBNP level. Despite the increase in heart rate, atrial pacing had no significant effect on cardiac output with exercise, owing to a decrease in stroke volume (−24 mL [95% CI, −43 to −5 mL]; P = .02). Adverse events judged to be related to the pacemaker device were observed in 6 of 29 participants (21%). Conclusions and Relevance In patients with HFpEF and chronotropic incompetence, implantation of a pacemaker to enhance exercise heart rate did not result in an improvement in exercise capacity and was associated with increased adverse events. Trial Registration ClinicalTrials.gov Identifier: NCT02145351

Background: The Acute Decompensated Heart Failure National Registry (ADHERE) Classification and Regression Tree (CART) algorithm is an accepted method to assess a heart failure (HF) patient’s risk of inpatient mortality based on the patient’s systolic blood pressure (≥115 vs. <115 mmHg), blood urea nitrogen (BUN; ≥43 vs. <43 mg/dL), and creatinine (≥2.75 vs. <2.75 mg/dL) at the time of admission. Whether the ADHERE CART algorithm identifies risk of longer term poor outcomes and is predictive in patients with systolic (EF < 50%) or diastolic (EF ≥ 50%) HF in the community is unclear. Methods: We identified all hospitalizations for a primary diagnosis of HF occurring between 2000-2013 in a community-based cohort living within 40 miles of Rochester, MN. Outcomes including length of stay, in-hospital mortality, 30 and 90 day post-discharge mortality and readmission for any cause at 30 and 90 days were compared across the ADHERE CART risk groups using logistic regression for the entire cohort and separately for systolic (EF < 50%) and diastolic (EF ≥ 50%) HF. Results: See Table. We examined 5,918 heart failure hospitalizations among 3,628 individual patients. Distribution of hospitalizations across the risk categories is shown in table. Length of stay, in-hospital mortality, 30 and 90 day mortality and 30 and 90 day readmission rates all increased with increasing ADHERE risk categories. Similar results were obtained separately for systolic and diastolic HF. Conclusion: The ADHERE CART algorithm is simple, uses data universally available on admission, and identifies groups that differ substantially in their post-discharge adverse outcomes regardless of HF type (systolic vs diastolic) in the community. The ADHERE CART algorithm may inform clinical decision regarding advanced HF treatments, end-of-life planning and care transition services in patients hospitalized for HF in the community.

Background The Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines (GWTG) registries have developed simple heart failure (HF) in-hospital mortality risk scores. We hypothesized that HF scores predictive of in-hospital mortality would perform as well for early postdischarge mortality risk stratification. Methods and Results In this single-center, community-based, retrospective study of all consecutive primary HF hospitalizations (6203 hospitalizations in 3745 patients) from 2000 to 2013, the ADHERE and GWTG risk scores were calculated from admission data. There were 176 (3.0%) and 399 (6.7%), 869 (14.7%), and 1272 (21.5%) deaths in-hospital and at 30, 90, and 180 days postdischarge, respectively. The GWTG but not ADHERE risk score was well calibrated for in-hospital mortality. Both the ADHERE (C statistic 0.66 and 0.67, 0.64, and 0.64) and GWTG (C statistic 0.74 and 0.73, 0.71, and 0.70) HF risk scores were similarly predictive of in-hospital and 30-, 90-, and 180-day postdischarge mortality. The ADHERE risk score identified 10% and the GWTG risk score identified 20% of hospitalizations where 180-day postdischarge mortality was 50%, a prognostic bench mark for hospice referral. In contrast, hospitalizations characterized as lowest risk by the ADHERE (57% of hospitalizations; 180-day mortality 16.2%) or GWTG score (20% of hospitalizations; 180-day mortality 8.0%) had substantially lower mortality (odds ratios high versus low risk of 5–8 [ADHERE] and 11–18 [GWTG] across time points; P <0.0001 for all). Conclusions The simple ADHERE and GWTG scores stratify hospitalized HF patients for both inpatient and early postdischarge mortality risk, allowing comprehensive risk assessment on admission.

Background: In patients with heart failure and preserved ejection fraction, little is known about the characteristics of, and outcomes in, those with and without diabetes mellitus. Methods: We examined clinical and echocardiographic characteristics and outcomes in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Ejection Fraction) according to history of diabetes mellitus. Cox regression models were used to estimate hazard ratios for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. Results: Overall, 1134 of 4128 patients (27%) had diabetes mellitus. Compared with those without diabetes mellitus, they were more likely to have a history of myocardial infarction (28% versus 22%), higher body mass index (31 versus 29 kg/m 2 ), worse Minnesota Living With Heart Failure score (48 versus 40), higher median N-terminal pro-B-type natriuretic peptide concentration (403 versus 320 pg/mL; all P <0.01), more signs of congestion, but no significant difference in left ventricular ejection fraction. Patients with diabetes mellitus had a greater left ventricular mass and left atrial area than patients without diabetes mellitus. Doppler E-wave velocity (86 versus 76 cm/s; P <0.0001) and the E/e’ ratio (11.7 versus 10.4; P =0.010) were higher in patients with diabetes mellitus. Over a median follow-up of 4.1 years, cardiovascular death or heart failure hospitalization occurred in 34% of patients with diabetes mellitus versus 22% of those without diabetes mellitus (adjusted hazard ratio, 1.75; 95% confidence interval, 1.49–2.05), and 28% versus 19% of patients with and without diabetes mellitus died (adjusted hazard ratio, 1.59; confidence interval, 1.33–1.91). Conclusions: In heart failure with preserved ejection fraction, patients with diabetes mellitus have more signs of congestion, worse quality of life, higher N-terminal pro-B-type natriuretic peptide levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes mellitus on outcomes in heart failure with preserved ejection fraction and whether they are modifiable. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00095238.