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.

Efficacy and Safety of Isoprenaline during Unstable Third-Degree Atrioventricular Block.

Unstable and symptomatic complete atrioventricular block represents a potentially fatal condition that requires prompt therapy while waiting for definitive pacemaker implantation. Although transcutaneous pacing is included in acute management, it could be a difficult approach due to its painfulness and the occasional failure of mechanical capture. Drug therapy is a feasible choice, and current guidelines encompass the use of atropine, dopamine, or epinephrine. Isoprenaline has never been investigated in this setting, and no specific indication of its use has been provided despite its potentially more favorable pharmacological profile. The study population included a consecutive series of patients who presented to the emergency department because of unstable third-degree atrioventricular block and were treated with either isoprenaline or dopamine infusion while waiting for definitive pacemaker implantation. Asymptomatic patients or those with reversible causes of complete atrioventricular block were excluded. The clinical response to the drug was deemed poor if, despite achieving a full drug dose, patients remained symptomatic and/or with hemodynamic instability, ventricular rate and rhythm did not improve or worsened, including if ventricular arrhythmias or asystolic pauses and/or irrepressible nausea/vomiting occurred. Isoprenaline infusion has proved to be safe and tolerated with no arrhythmia induction or hypotensive issues. Isoprenaline has also proven to be more satisfactory in achieving an effective clinical response in 84% of patients rather than dopamine (31%, p < 0.001), reducing the need for temporary artificial pacing. Our data point out the efficacy and safety of isoprenaline infusion and its greater tolerability over dopamine in the acute management of unstable third-degree AV block while waiting for definitive pacemaker implantation.

Slow Continuous Ultrafiltration in Regional Citrate Anticoagulation Performed with a Standard Fluid Infusion Central Venous Catheter in Intensive Care Unit for Fluid Overload in Acute on Chronic Heart Failure: A Case Report.

Slow continuous ultrafiltration (SCUF) is an extracorporeal therapy able to reduce fluid overload in chronic or acute heart failure resistant to diuretics. An in-vitro study demonstrated the SCUF feasibility using a standard fluid infusion central venous catheter (CVC). We describe the clinical application of this SCUF in regional citrate anticoagulation (SCUF-RCA) in a patient admitted to the Intensive Care Unit for acute decompensate heart failure with severe systemic fluid overload resistant to diuretics. To avoid risks deriving from a new catheterization, we used a pre-existing multi-lumen CVC for drug administration to provide 10 h of SCUF-RCA with a blood flow of 35 mL/min and 100 mL/h of ultrafiltration with a final weight loss of 1 Kilogram without technical and clinical complications. The patient had a hemodynamics improvement with the diuresis recovery from the previous oliguria after the SCUF-RCA. This clinical case can open the use of the SCUF-RCA in the clinical practice to treat the fluid overload unresponsive to maximal diuretic therapy not exposing the patient to the risks and complications related to the use of SCUF with CVC for dialysis and systemic anticoagulation with heparin. Accordingly, this technique may be useful in the treatment of fluid overload in outpatients.

Structural Cardiac Abnormalities in Patients with Atrial Fibrillation/Flutter and Myocardial Injury.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTnT) is often increased in patients with atrial fibrillation/flutter, portending a poor prognosis. The etiologies for these increases have not been systematically investigated. Our aim was to define prevalence/significance of structural cardiac abnormalities in patients with atrial fibrillation/flutter and high-sensitivity cardiac troponin T (hs-cTnT) increases. METHODS: This is a retrospective observational cohort study of patients with atrial fibrillation/flutter diagnosis with hs-cTnT measurements, echocardiograms, and coronary angiograms. Myocardial injury was defined as hs-cTnT >10 ng/L for women and >15 ng/L for men. Cases with myocardial injury were adjudicated according to the Fourth Universal Definition of Myocardial Infarction. RESULTS: Patients with definite causes for increased hs-cTnT (n = 875) were tabulated but not evaluated further; common diagnoses were type 1 myocardial infarction, critical illness, and known heart failure. Of the remaining 401, increased hs-cTnT was present in 336 (84%) patients. Of those, 78% had nonischemic myocardial injury, the remaining (n = 75, 22%) had type 2 myocardial infarction. Patients with elevated hs-cTnT had greater left ventricular mass index, left ventricular filling pressures, and right ventricular systolic pressure. They more frequently had significant coronary artery disease (47% vs 31%, P = .016), especially in type 2 myocardial infarction. With logistic regression, age, sex (F), diabetes, left ventricular mass index, e' medial velocity, and right ventricular systolic pressure were independent determinants of myocardial injury. One-year mortality was higher in patients with myocardial injury. CONCLUSIONS: Structural heart abnormalities are common in patients with atrial fibrillation/flutter and increased hs-cTnT. Causes of myocardial injury should be elucidated in each patient to craft appropriate therapies.

Using high sensitivity cardiac troponin values in patients with SARS-CoV-2 infection (COVID-19): The Padova experience.

BACKGROUND: The spectrum of Coronavirus Disease 2019 (COVID-19) is broad and thus early appropriate risk stratification can be helpful. Our objectives were to define the frequency of myocardial injury using high-sensitivity cardiac troponin I (hs-cTnI) and to understand how to use its prognostic abilities. METHODS: Retrospective study of patients with COVID-19 presenting to an Emergency Department (ED) in Italy in 2020. Hs-cTnI was sampled based on clinical judgment. Myocardial injury was defined as values above the sex-specific 99th percentile upper reference limits (URLs). Most data is from the initial hospital value. RESULTS: 426 unique patients were included. Hs-cTnI was measured in 313 (73.5%) patients; 85 (27.2%) had myocardial injury at baseline. Patients with myocardial injury had higher mortality during hospitalization (hazard ratio = 9 [95% confidence interval (CI) 4.55-17.79], p < 0.0001). Multivariable analysis including clinical and laboratory variables demonstrated an AUC of 0.942 with modest additional value of hs-cTnI. Myocardial injury was associated with mortality in patients with low APACHE II scores (<13) [OR (95% CI): 4.15 (1.40, 14.22), p = 0.014] but not in those with scores > 13 [OR (95% CI): 0.48 (0.08, 2.65), p = 0.40]. Initial hs-cTnI < 5 ng/L identified 33% of patients that were at low risk with 97.8% sensitivity (95% CI 88.7, 99.6) and 99.2% negative predictive value. Type 1 myocardial infarction (MI) and type 2 MI were infrequent. CONCLUSIONS: hs-cTnI at baseline is a significant predictor of mortality in COVID-19 patients. A value < 5 ng/L identified patients at low risk.

Fulminant myocarditis parvovirus B19 related in a young woman.

We present the case of a 18-year-old female with fulminant lymphocytic myocarditis caused by Parvovirus B19 (PVB19), successfully treated using temporary LVAD. In the literature there is no consensus on the surgical strategy. While some surgeons prefer to use a single device supporting only the LV, others prefer to start immediately with a biventricular supporting. At pre-procedural ultrasound evaluation, her anatomical features were not suitable for a percutaneous device such as the Impella. Thus, a temporary paracorporeal continuous flow LVAD was inserted. The heart recovery allowed LVAD removal 9 days after the implant.

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.

Cardiac troponin I in SARS-CoV-2-patients: The additional prognostic value of serial monitoring.

BACKGROUND: Major cardiac complications have been described in SARS-CoV-2 patients. The study of cardiac troponin' kinetic release is the recommended approach to differentiate acute from chronic injury, in order to clinically manage different cardiac diseases. AIM: To investigate whether serial measurements of high sensitivity troponin I (hs-cTnI) might provide additional information in SARS-CoV-2 patients's clinical management. METHODS: 113 consecutive patients suffering from microbiology proven SARS-CoV2-infection have been studied. Hs-cTnI has been measured in lithium-heparin plasma samples using STAT High Sensitive Troponin I (Architect i2000, Abbott Diagnostics), being 99th percentiles 16 and 34 ng/L for females and males respectively. RESULTS: In 69 out of 113 patients hs-cTnI has been measured, showing in 31 (45%) values higher than 99th percentiles in at least one occasion. In 50 patients (72%) a kinetic evaluation (at least 2 measurements during 24 h) has been carried out. Patients were subdivided into five groups: 1 (n = 44) and 2 (n = 19) no measurement of hs-cTnI or no monitoring respectively; 3 (n = 15) no significant variations during monitoring; 4 (n = 8) and 5 (n = 27) significant variations with values persistently below or sometimes higher than 99th percentiles, respectively. Group 5 patients had a longer hospital stay (median 37 days, p = 0.0001), a more aggressive disease (6 out of 27, 22%, died), more often need admission to ICU (n = 25, 92.6%, p < 0.0001), and show one or more peak values, sometime preceded by severe hypoxia. CONCLUSIONS: In SARS-CoV-2 patients, hs-cTnI serial monitoring may provide additional data to stratify risk, establish prognosis and gaining epidemiological insight on cardiac involvement in this pandemic disease.

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).

The benefit of betrixaban for the extended thromboprophylaxis in acutely ill medical patients.

INTRODUCTION: Patients admitted with acute medical conditions are at prolonged risk for venous thrombosis. The efficacy and safety, and the appropriate duration of thromboprophylaxis have not been clearly determined. In recent years, direct coagulation factor inhibitors have been successfully tested for the prevention and treatment of arterial and venous thromboembolism. Betrixaban is a novel direct inhibitor of factor Xa with a noteworthy pharmacological feature: limited renal clearance. Areas covered: This review focuses on the pharmacological profile of Betrixaban, including its clinical efficacy and safety. It also covers the results of the pivotal APEX trial assessing the safety and efficacy of betrixaban for extended thromboprophylaxis in patients with acute medical conditions. Expert opinion: The role of extended thromboprophylaxis in acutely ill medical patients is subject to debate. The beneficial results in terms of VTE prevention were offset by the relevant increase in major bleeding. Betrixaban is the only direct oral anticoagulant to have shown a favorable risk-benefit profile in this setting especially in patients at higher risk for thrombosis.

Prognostic value of cardiac troponin I assay in hospitalized elderly patients.

BACKGROUND: Cardiac troponin I (cTnI) has been poorly studied in elderly inpatients. AIM: This study wanted to assess factors influencing the increase in cTnI and its prognostic value in hospitalized elderly patients. METHODS: 354 elderly (mean age of 84.8 ± 6.9 years) patients consecutively admitted in the Geriatrics Division in Padua were tested for cTnI levels assay during the hospital stay. Number of subsequent patient deaths at 6 months and 2 years were registered. RESULTS: Of the 354 patients, 27 (7.6%) died in hospital; their levels were not significantly higher or more frequently positive on cTnI than those of the remainder of the sample. 71 (20.01%) patients died within 6 months of being discharged, and in-hospital positive cTnI levels emerged as a mortality risk factor in this group [unadjusted HR 1.13 (1.04-1.23); p = 0.004]. At 2 years, a total of 174 patients (49.2%) had died, but in-hospital pathological cTnI levels were not a mortality risk factor in this group. DISCUSSION: It should be noted that cTnI level was a risk factor for mortality at 6 months but no longer at 2 years after an elderly patient's hospitalization. This finding may relate to patients' limited physiological reserves or be driven by the fact that the elderly tend to receive fewer evidence-based treatments, and to be managed more conservatively than younger patients. CONCLUSIONS: In the multidimensional analysis of older patients, troponin I can be used to stratify patients and assess mortality risk at 6 months, but not at 2 years.

Renal Dysfunction: How to Think About That in Acute Coronary Syndromes.

PURPOSE OF REVIEW: Reduction of kidney function and heart disease frequently coexisted in the seam patient. The relation between renal and heart function is quite complex and bring out some unresolved questions about diagnosis (mostly related to the biomarkers levels interpretation), pharmacological therapy (mostly related to drugs kinetics and efficacy), and non-pharmacological therapy. RECENT FINDINGS: Patients with kidney dysfunction (KD) are frequently excluded and underrepresented in the large trials. It is well-known that coronary revascularization reduces mortality also in KD patients presenting with acute coronary syndrome. However, acute kidney injury (AKI), primarily related at contrast medium administration, is worse prognosis. For this reason, prevention, early diagnosis, and effective therapy of ACK are key elements in assistance of these patients. In this context, recently, some new biomarkers of renal function have been proposed. Frequently, patients with acute coronary syndromes and kidney disease are undertreated, worsening their prognosis. Undertreatment and comorbidities associated with renal dysfunction explain the higher mortality of these patients.

Argatroban in the management of heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immunoglobulin-mediated serious complication of heparin therapy characterized by thrombocytopenia and high risk for venous and arterial thrombosis: HIT and thrombosis syndrome (HITTS). Argatroban, a direct thrombin inhibitor, is indicated as the anticoagulant for the treatment and prophylaxis of thrombosis in patients with HIT and in patients undergoing percutaneous coronary intervention (PCI) who have HIT. The aim of this review is to examine the pharmacological characteristics and the clinical efficacy and safety of this drug in adults with HIT, including those undergoing PCI. Briefly, 2 prospective multicenter, nonrandomized, open-label studies evaluated the efficacy and safety of argatroban as an anticoagulant in patients with HIT or HITTS. Both studies showed that the incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced in argatroban-treated patients vs control subjects with HIT or HITTS. In both studies, bleeding rates were similar between the groups. Argatroban was evaluated as the anticoagulant therapy in 3 prospective, multicenter, open-label studies in HIT patients who underwent PCI. The studies were similar in design with respect to patient inclusion and exclusion criteria, the argatroban dosing regimen, and primary efficacy outcomes. The investigators performed a pooled analysis of these studies, which showed that most (≥95%) patients achieved a satisfactory outcome from the procedure and adequate anticoagulation (coprimary end points).

Design and methodologies of the POSTconditioning during coronary angioplasty in acute myocardial infarction (POST-AMI) trial.

BACKGROUND: Reperfusion remains the definitive treatment for acute myocardial infarction (AMI), but restoring blood flow carries the potential to exacerbate the ischemia-related injury. Postconditioning might modify reperfusion-induced adverse events. STUDY DESIGN: The POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) trial is a single-center, prospective, randomized study, with a planned inclusion of 78 patients with ST-elevation AMI. Patients will be randomly assigned to the postconditioning arm [primary angioplasty (PA) and stenting followed by brief episodes of ischemia-reperfusion early after recanalization] or non-postconditioning arm. All patients will be treated medically according to current international guidelines, including glycoprotein IIb/IIIa inhibitors before PA. The primary end point is to evaluate whether postconditioning, compared to plain PA, reduces infarct size estimated by cardiac magnetic resonance (CMR) at 30 +/- 10 days after the AMI. Secondary end points are microvascular obstruction observed at CMR, ST-segment resolution, angiographic myocardial blush grade <2, non-sustained/sustained ventricular tachycardia in the 48 h following PA, left ventricular remodeling and function at follow-up CMR, and the reduction of major adverse cardiac events at 30 days and 6 months. CONCLUSION: The POST-AMI trial will evaluate the usefulness of postconditioning in limiting infarct size during the early and late phases after AMI.

Aborted myocardial infarction: is it real in the troponin era?

BACKGROUND: Cardiac troponins are the markers of choice for the diagnosis of acute myocardial infarction. The objective of this study was to compare the frequency of "aborted myocardial infarction" (no detectable myocardial injury) determined by measurement of troponin versus that determined by creatine kinase (CK) and creatine kinase-muscle brain (CK-MB) measurement criteria among patients with ST-elevation myocardial infarction (STEMI) who received reperfusion therapy. METHODS: Since 2004, the Mayo Clinic (Rochester, MN) has had a standard reperfusion protocol for the treatment of patients with STEMI. During the study period, 767 patients presented with new or presumed new ST elevation or left bundle block. RESULTS: The diagnosis of STEMI was confirmed in 765 (99.7%) patients. Using the 99th percentile cutoff value, troponin T elevations occurred in 765 (100%) of 765 patients when serial samples were available. Creatine kinase-MB levels of twice or more the upper limit of normal occurred in 681 (90.1%) of 749 patients with serial samples for CK-MB, and CK equal or greater than twice the gender-specific upper limits of normal occurred in 521 (78.8%) of 661 patients with serial samples for CK available. CONCLUSION: The frequency of aborted myocardial infarction is 0% when using troponin at the 99th percentile cutoff as recommended by contemporary guidelines from the European Society of Cardiology (Nice, France) and American College of Cardiology (Washington, DC).

Long-term prognostic significance of elevated cardiac troponin levels in critically ill patients with acute gastrointestinal bleeding.

BACKGROUND: Elevations in troponin level have prognostic importance in critically ill patients, including those with gastrointestinal (GI) bleeding. However, there are no data addressing the independent association of troponin levels and mortality, adjusted for the severity of the underlying disease, in patients with GI bleeding. OBJECTIVE: This study was designed to determine whether troponin T elevations are independently associated with in-hospital, short-term (30 days), and long-term mortality in medical intensive care unit patients with GI bleeding after adjusting for the severity of disease measured by the Acute Physiology, Age, and Chronic Health Evaluation score prognostic system. DESIGN: Retrospective study. SETTING: We examined the Acute Physiology, Age, and Chronic Health Evaluation III database and cardiac troponin T levels from patients consecutively admitted to the medical intensive care unit at Mayo Clinic, Rochester, MN, with acute GI bleeding. PATIENTS: Between August 2000 and July 2005, 1076 patients with acute GI bleeding consecutively admitted to the medical intensive care units. MEASUREMENTS: In-hospital, short-term (30 days), and long-term all-cause mortality. RESULTS: During hospitalization, 8.0% of deaths occurred in patients with troponin T < 0.01% and 11.9% with troponin T > or = 0.01 (p = 0.083). At 30 days, mortality was 10.1% and 18.8% in patients without and with elevations of troponins, respectively (p < 0.001). The Kaplan-Meier expected probability of survival at 1-, 2-, and 3-yr follow-up was 54.2%, 40.8%, and 30.4% with troponin T > or = 0.01 microg/L and 78.3%, 69.3%, and 61.5% with troponin T < 0.01 microg/L (p < 0.001). After adjustment for severity of disease and baseline characteristics, cardiac troponin levels were associated only with long-term mortality (p < 0.001). LIMITATIONS: This is a retrospective, single-center study which included only patients in whom troponin level was determined upon admission. CONCLUSIONS: In patients with GI bleeding severe enough to require admission to the medical intensive care unit, admission troponin T elevations are associated with long-term but not short-term mortality.