Respiratory exchange ratio overshoot during exercise recovery: a promising prognostic marker in HFrEF.

BACKGROUND AND AIMS: Transient increases (overshoot) in respiratory gas analyses have been observed during exercise recovery, but their clinical significance is not clearly understood. An overshoot phenomenon of the respiratory exchange ratio (RER) is commonly observed during recovery from maximal cardiopulmonary exercise testing (CPET), but it has been found reduced in patients with heart failure with reduced ejection fraction (HFrEF). The aim of the study was to analyze the clinical significance of these RER recovery parameters and to understand if these may improve the risk stratification of patients with HFrEF. METHODS: This cross-sectional study includes HFrEF patients who underwent functional evaluation with maximal CPET for the heart transplant checklist at our Sports and Exercise Medicine Division. RER recovery parameters, including RER overshoot as the percentual increase of RER during recovery (RER mag), have been evaluated after CPET with assessment of hard clinical long-term endpoints (MACEs/deaths and transplant/LVAD-free survival). RESULTS: A total of 190 patients with HFrEF and 103 controls were included (54.6 ± 11.9 years; 73% male). RER recovery parameters were significantly lower in patients with HFrEF compared to healthy subjects (RER mag 24.8 ± 14.5% vs 31.4 ± 13.0%), and they showed significant correlations with prognostically relevant CPET parameters. Thirty-three patients with HFrEF did not present a RER overshoot, showing worse cardiorespiratory fitness and efficiency when compared with those patients who showed a detectable overshoot (VO2 peak: 11.0 ± 3.1 vs 15.9 ± 5.1 ml/kg/min; VE/VCO2 slope: 41.5 ± 8.7 vs 32.9 ± 7.9; ΔPETCO2: 2.75 ± 1.83 vs 4.45 ± 2.69 mmHg, respectively). The presence of RER overshoot was associated with a lower risk of cardiovascular events and longer transplant-free survival. CONCLUSION: RER overshoot represents a meaningful cardiorespiratory index to monitor during exercise gas exchange evaluation; it is an easily detectable parameter that could support clinicians to comprehensively interpreting patients' functional impairment and prognosis. CPET recovery analyses should be implemented in the clinical decision-making of advanced HF.

Characteristics and hospital course of patients admitted for acute cardiovascular diseases during the coronavirus disease-19 outbreak.

INTRODUCTION: During the coronavirus disease-19 (COVID-19) outbreak in spring 2020, people may have been reluctant to seek medical care fearing infection. We aimed to assess the number, characteristics and in-hospital course of patients admitted for acute cardiovascular diseases during the COVID-19 outbreak. METHODS: We enrolled all consecutive patients admitted urgently for acute myocardial infarction, heart failure or arrhythmias from 1 March to 31 May 2020 (outbreak period) and 2019 (control period). We evaluated the time from symptoms onset to presentation, clinical conditions at admission, length of hospitalization, in-hospital medical procedures and outcome. The combined primary end point included in-hospital death for cardiovascular causes, urgent heart transplant or discharge with a ventricular assist device. RESULTS: A similar number of admissions were observed in 2020 (N = 210) compared with 2019 (N = 207). Baseline characteristics of patients were also similar. In 2020, a significantly higher number of patients presented more than 6 h after symptoms onset (57 versus 38%, P < 0.001) and with signs of heart failure (33 versus 20%, P = 0.018), required urgent surgery (13 versus 5%, P = 0.004) and ventilatory support (26 versus 13%, P < 0.001). Hospitalization duration was longer in 2020 (median 10 versus 8 days, P = 0.03). The primary end point was met by 19 (9.0%) patients in 2020 versus 10 (4.8%) in 2019 (P = 0.09). CONCLUSION: Despite the similar number and types of unplanned admissions for acute cardiac conditions during the 2020 COVID-19 outbreak compared with the same period in 2019, we observed a higher number of patients presenting late after symptoms onset as well as longer and more complicated clinical courses.

Timing of Oral P2Y12 Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Although oral P2Y12 inhibitors are key in the management of patients with non-ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined. OBJECTIVES: The purpose of this study was to compare downstream and upstream oral P2Y12 inhibitors administration strategies in patients with non-ST-segment elevation acute coronary syndrome undergoing invasive treatment. METHODS: We performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit). RESULTS: We randomized 1,449 patients to downstream or upstream oral P2Y12 inhibitor administration. A pre-specified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke; and Bleeding Academic Research Consortium type 3, 4, and 5 bleeding through day 30, did not differ significantly between the downstream and upstream groups (percent absolute risk reduction: -0.46; 95% repeated confidence interval: -2.90 to 1.90). These results were confirmed among patients undergoing percutaneous coronary intervention (72% of population) and regardless of the timing of coronary angiography (within or after 24 h from enrollment). CONCLUSIONS: Downstream and upstream oral P2Y12 inhibitor administration strategies were associated with low incidence of ischemic and bleeding events and minimal numeric difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of 1 strategy over the other. (Downstream Versus Upstream Strategy for the Administration of P2Y12 Receptor Blockers In Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication [DUBIUS]; NCT02618837).

Vascular surgery patients: perioperative and long-term risk according to the ACC/AHA guidelines, the additive role of post-operative troponin elevation.

AIMS: The objectives of this study are to evaluate the prognostic role of pre-operative stratification in patients undergoing elective major vascular surgery, the timing of adverse outcomes, and the predictive role of troponin (cTn). METHODS AND RESULTS: Consecutive vascular surgery candidates (n=391) were prospectively stratified and treated according to the ACC/AHA guidelines. The patients were categorized into three groups: (1) with coronary revascularization in the past 5 years, (2) with intermediate clinical risk predictors, and (3) with minor or no clinical risk predictors. cTnI was measured post-operatively. By 18 months, 18.7% of subjects had experienced death or acute myocardial infarction (MI) (by the ACC/ESC criteria). The hazard ratio (HR) was 5.21 (95% CI=2.60-10.43; P<0.0001) in group 1 and 2.58 (95% CI=1.27-4.38; P=0.004) in group 2 when compared with group 3. Most events occurred within 30 days. Elevations of cTnI were associated with adverse outcomes even after multivariable adjustment at long-term (adjusted overall HR=4.73, 95% CI=2.92-7.65; P<0.0001) and at 30 days (adjusted HR=5.52, 95% CI=3.23-9.42; P<0.0001). CONCLUSION: After pre-operative stratification, patients undergoing elective major vascular surgery remain at high risk of MI and death. Events occur mainly early after surgery. cTnI elevations are frequent and independently associated with increased risk. These findings suggest the need for a major re-evaluation of our approach to these patients.