Exercise intolerance is a hallmark feature in heart failure with preserved ejection fraction (HFpEF). Prior heavy exercise (“priming exercise”) speeds pulmonary oxygen uptake (V̇o2p) kinetics in older adults through increased muscle oxygen delivery and/or alterations in mitochondrial metabolic activity. We tested the hypothesis that priming exercise would speed V̇o2p on-kinetics in patients with HFpEF because of acute improvements in muscle oxygen delivery. Seven patients with HFpEF performed three bouts of two exercise transitions: MOD1, rest to 4-min moderate-intensity cycling and MOD2, MOD1 preceded by heavy-intensity cycling. V̇o2p, heart rate (HR), total peripheral resistance (TPR), and vastus lateralis tissue oxygenation index (TOI; near-infrared spectroscopy) were measured, interpolated, time-aligned, and averaged. V̇o2p and HR were monoexponentially curve-fitted. TPR and TOI levels were analyzed as repeated measures between pretransition baseline, minimum value, and steady state. Significance was P < 0.05. Time constant (τ; tau) V̇o2p (MOD1 49 ± 16 s) was significantly faster after priming (41 ± 14 s; P = 0.002), and the effective HR τ was slower following priming (41 ± 27 vs. 51 ± 32 s; P = 0.025). TPR in both conditions decreased from baseline to minimum TPR ( P < 0.001), increased from minimum to steady state ( P = 0.041) but remained below baseline throughout ( P = 0.001). Priming increased baseline ( P = 0.003) and minimum TOI ( P = 0.002) and decreased the TOI muscle deoxygenation overshoot ( P = 0.041). Priming may speed the slow V̇o2p on-kinetics in HFpEF and increase muscle oxygen delivery (TOI) at the onset of and throughout exercise. Microvascular muscle oxygen delivery may limit exercise tolerance in HFpEF.

We present the case of a 50-year-old man presenting with fever, back pain, persistent bacteremia with Veillonella dispar , echocardiographic evidence of a tricuspid valve vegetation increasing in size, and magnetic resonance imaging suggesting new vertebral osteomyelitis. He was successfully treated with intravenous ceftriaxone for six weeks. Deep-seated infections secondary to Veillonella species are rare, but cases of endocarditis, osteomyelitis, and meningitis have been reported in the literature. Given Veillonella species are normal human commensals present in the oropharyngeal flora, we suspect our patient developed native tricuspid valve endocarditis and vertebral osteomyelitis as a complication of either poor dentition or contaminated injection drug use paraphernalia and subsequent hematogenous seeding.

Background: Although several factors have been cited for risk stratification in patients with simple transposition of the great arteries (dTGA), no single predictor emerges consistently. We aimed to assess survival and determine factors associated with survival in a large cohort of dTGA adults with atrial switch. Methods and Results: We included 1,169 dTGA adults (median age 28.1 years, 38.7% female) under regular follow-up at 28 institutions between 2002 and 2019. The primary outcome was a composite of death, mechanical circulatory support (MCS) and heart transplant. During a median follow-up of 9.2 [IQR 5.5-14.2] years, 67 (5.7%) patients died, six (0.5%) patients underwent MCS and 21 (1.8%) had a heart transplant. Cumulative incidence of composite endpoint at 15 years was 12.8% [95% CI 9.8 - 15.7], see Figure). Median age at time of primary outcome was 39.5 [IQR 33.9 - 45.1] years. Leading causes of death were worsening of heart failure (34%), non-cardiac (21%) and sudden unexplained death (12%). In multivariable Cox analyses for baseline variables, age, VSD, ventricular arrhythmia and heart failure admission were each associated with increased risk of the outcome, whereas prior pacemaker (26% of patients) was not. New pacemaker implantation was performed in 107 (9.1%), ICD in 109 (9.3%), and cardiac surgery in 35 (3%) patients. Patients who died were more likely to develop arrhythmias, be admitted for heart failure or require surgery during follow-up. Conclusion: In this large contemporary cohort of dTGA adults after atrial switch, late survival was excellent and seemed to be determined by arrhythmia and heart failure-related complications. Few patients underwent advanced heart failure therapies. Figure. Cumulative incidence of the composite primary outcome (MCS, heart transplant or death) over a period of 15 years from first visit at an adult congenital heart disease clinic since 2002. Shading represents upper and lower 95% confidence limits.

Background: Occasionally patients with congenitally corrected transposition of the great arteries (ccTGA) exhibit little clinical evidence of cardiovascular limitation even to their 8th decade. We aimed to assess survival prospects in a large cohort of ccTGA adults. Methods & Results: We included 555 ccTGA adults (median age 33.0 years, 48.3% female) under regular follow-up at 28 institutions between 2002 and 2019. The primary outcome was a composite of death, mechanical circulatory support (MCS) and heart transplant. During a median follow-up of 8.1 [IQR 4.4 - 13.3] years, 56 (10.1%) patients died, 10 (1.8%) patients underwent MCS and 14 (2.5%) had a heart transplant. Median age at time of primary outcome was 51.1 [IQR 37.5 - 63.2] years and cumulative incidence at 15 years from baseline was 21.5% [95% CI 16.1 - 26.5]. Leading causes of death were worsening of heart failure (43%) and sudden death (10%). Patients who died were more likely to use heart failure (HF) medications. In multivariable Cox analyses for baseline variables, age, prior atrial arrhythmia and HF admission were each associated with an increased risk of the primary outcome. Figure shows cumulative incidence according to history of atrial arrhythmia. During follow-up, 91 (16.4%) were admitted for HF, pacemaker implantation was performed in 68 (12.3%) patients, ICD in 82 (14.7%), and major cardiac surgery (mostly for systemic AV-valve) in 89 (15.8%) patients. Conclusion: In this large cohort of ccTGA adults, survival seemed to be primarily determined by heart failure-related complications. Prior atrial arrhythmia also seems to be a harbinger for adverse outcome. Few patients underwent advanced HF therapies. Figure: Cumulative incidence of the composite primary outcome (MCS, heart transplant or death) over a period of 14 years from first visit at an adult congenital heart disease clinic since 2002 stratified according to history of atrial arrhythmia. Shading represents upper and lower 95% confidence limits.

Exercise intolerance and muscle dysfunction characterize heart failure with preserved ejection fraction (HFpEF). Prior heavy exercise (“priming”) speeds pulmonary oxygen uptake (V̇O2p) kinetics in older adults. The mechanism behind speeding of V̇O2p kinetics following priming is either through increased oxygen delivery to the exercising muscles or increased intracellular metabolic activity; the former remains dominant in older and diseased populations.PURPOSEWe tested the hypothesis that priming would not speed V̇O2p on‐kinetics in patients with HFpEF due to muscle dysfunction commonly found in patients with HFpEF.METHODSEight HFpEF patients, 4 high‐fit (CTL‐HF), and 5 low‐fit age‐matched controls (CTL‐LF) performed 3 repetitions of 2 exercise transitions: MOD1, rest to 4‐min moderate‐intensity cycling; and MOD2, MOD1 preceded by 2‐min heavy‐intensity cycling and 5‐min rest. V̇O2p (oxidative metabolism; pulmonary gas exchange), heart rate (HR, cardiac function; ECG), total peripheral resistance (TPR, vascular function; ModelFlow), and tissue oxygenation of the vastus lateralis (TOI, muscle oxygen delivery; near‐infrared spectroscopy) on‐kinetics were measured, linearly interpolated, time‐aligned, and averaged. V̇ O2p and HR were curve‐fitted using a monoexponential equation to yield a time constant (tau). ΔTPR and ΔTOI were calculated from baseline at 15s, 30s, and end‐exercise. Significance was P<0.05.RESULTSHFpEF V̇O2p on‐kinetics (tau 45 ± 15 s) were slower than CTL‐HF (25 ± 6 s) but not CTL‐LF (50 ± 19 s; P=0.008). MOD2 V̇O2p on‐kinetics (tau 37 ± 14 s) were faster than MOD1 (47 ± 19 s), pooled across groups (P=0.039). Although not statistically significant, the priming effect was notably smaller in HFpEF compared to control groups (9% in HFpEF, 33% in low‐fit controls, and 30% faster in high‐fit controls). HR on‐kinetics were slower following priming in all groups (MOD1 tau 34 ± 21 vs. MOD2 44 ± 27 s; P=0.001), suggesting cardiac output as an unlikely assistant to the observed speeding in V̇O2p on‐kinetics across groups. TPR was lower in CTL‐HF throughout exercise compared to HFpEF (all P<0.038) and at 30s and end‐exercise compared to CTL‐LF (all P<0.032), pooled across conditions with no effect of priming. TOI in CTL‐HF increased at 15–30s (all P≤0.024) while HFpEF patients and CTL‐LF had decreased TOI at 15–30s in MOD1 (all P≤0.024). The latter suggests lower oxygen delivery at early exercise onset compared to CTL‐HF. Priming reduced TOI in HFpEF at 30s (P=0.033) and CTL‐HF throughout exercise (all P<0.05), suggesting either lower muscle oxygen delivery or greater mitochondrial activity following priming.CONCLUSIONSlow HFpEF V̇O2p on‐kinetics may not be speeded by priming exercise. Heart rate and vascular responses to priming may not account for speeding of V̇O2p on‐kinetics in older adults. Intracellular mechanisms may limit HFpEF exercise tolerance.Support or Funding InformationCanadian Institutes of Health ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.