Use of extracorporeal membrane oxygenation in high-risk acute pulmonary embolism: A systematic review and meta-analysis.

Extracorporeal membrane oxygenation (ECMO) represents a therapeutic option for cardiopulmonary support in patients with high-risk pulmonary embolism (PE); however, no definite consensus exists on ECMO use in high-risk PE. Hence, we aim to provide insights into its real-world use pooling together all available published experiences. We performed a systematic review and pooled analysis of all published studies (up to April 17, 2020) investigating ECMO support in high-risk PE. All studies including at least four patients were collectively analyzed. Study outcomes were early all-cause death (primary endpoint) and relevant in-hospital adverse events. A total of 21 studies were included in the pooled analysis (n = 635 patients). In this population (mean age 47.8 ± 17.3 years, 44.5% females), ECMO was indicated for cardiac arrest in 62.3% and immediate ECMO support was pursued in 61.9% of patients. Adjunctive reperfusion therapies were implemented in 57.0% of patients. Pooled estimate rate of early all-cause mortality was 41.1% (95% CI 27.7%-54.5%). The most common in-hospital adverse event was major bleeding, with an estimated rate of 28.6% (95%CI 21.0%-36.3%). At meta-regression analyses, no significant impact of multiple covariates on the primary endpoint was found. In this systematic review of patients who received ECMO for high-risk PE, pooled all-cause mortality was 41.1%. Principal indication for ECMO was cardiac arrest, cannulation was chiefly performed at presentation, and major bleeding was the most common complication.

Anti-ß-adrenoceptors autoimmunity causing 'idiopathic' arrhythmias and cardiomyopathy.

BACKGROUND: To determine the prevalence of anti-ß-adrenoceptors autoantibodies (aßAA) in patients with idiopathic arrhythmias (IA) and to assess whether aßAA are predictive markers for concealed cardiomyopathy in such patients. METHODS AND RESULTS: Sixty-seven patients (group 1) with IA [25 supraventricular (SVA) and 42 ventricular (VA)]; 14 patients (group 2) with suspected cardiomyopathy, 12 patients with definite cardiomyopathy (group 3); and 19 healthy controls (group 4) were tested with an enzyme immunoassay, using synthetic peptides corresponding to the second extracellular loop of the human ß1-and ß2-adrenoceptors. Endomyocardial biopsy was performed in 29 patients. As compared with group 4 [3/19 (15.7%)], anti-ß1-adrenoceptor autoantibodies (aß1AA) were more frequent in group-1 patients [38/67 (56.7%; P<0.01): 27/42 (64.2%; P<0.001) with VA and 11/25 (44%; P<0.05) with SVA]. 3 of the group 1 patients also had anti-ß2-adrenoceptor autoantibodies (aß2AA). 4 were positive for aß2AA only. Biopsy performed in 11/67 group 1 patients was abnormal in all. Of them, 7/8 (87.5%) with VA and 3/3 (100%) with SVA were positive for aß1AA. PCR analysis from paraffin blocks of the 11 group 1 biopsied patients was negative for EV, EBV, HCV, AV, PVB19, INF A/B,HSV1/2, HHV6 and HHV8 viral genomes. CONCLUSIONS: The second extracellular loop of the ß-adrenoceptor is the molecular target of specific autoantibodies. Positivity for aß1AA predicts abnormal histological findings in 90% of IA patients and suggests that autoimmunity might play an arrhythmogenic role.

Prognostic value of right atrial pressure-corrected cardiac power index in cardiogenic shock.

AIM: The pulmonary artery catheter (PAC)-derived cardiac power index (CPI) has been found of prognostic value in cardiogenic shock (CS) patients. The original CPI equation included the right atrial pressure (RAP), accounting for heart filling pressure as a determinant of systolic myocardial work, but this term was subsequently omitted. We hypothesized that the original CPI formula (CPIRAP ) is superior to current CPI for risk stratification in CS. METHODS AND RESULTS: A single-centre cohort of 80 consecutive Society for Cardiovascular Angiography and Interventions (SCAI) B-D CS patients with available PAC records was included. Overall in-hospital mortality was 21.3%. Results showed CPIRAP to be the strongest haemodynamic predictor of in-hospital death (padj  = 0.038), outperforming CPI [area under the receiver operating characteristic (ROC) curves: 0.726 and 0.673, P-for-difference = 0.025]. When the population was stratified according to the identified CPIRAP (0.28 W/m2 ) and accepted CPI (0.32 W/m2 ) thresholds, the cohort with discordant indexes (low CPIRAP and high CPI) comprised a group of 13 patients featuring a congested phenotype with frequent right ventricle or biventricular involvement. In this group, in-hospital mortality was high (30.8%) similar to those with concordant low CPI and CPIRAP . CONCLUSION: Incorporating RAP in CPI calculation (CPIRAP ) improves the prognostic yield in patients with CS SCAI B-D. A cut-off of 0.28 W/m2 identifies patients at higher risk of in-hospital mortality. The improved prognostic value of CPIRAP may derive from identification of patients with more intravascular congestion who may experience substantial in-hospital mortality, uncaptured by the commonly used CPI equation.

Meta-Analysis Comparing P2Y12 Inhibitors in Acute Coronary Syndrome.

Dual antiplatelet therapy combining aspirin with a P2Y12-receptor inhibitor reduces atherothrombotic events following an acute coronary syndromes (ACS), but the relative merits of different P2Y12 inhibitors remain unclear, despite several recent large-scale trials. We performed a network meta-analysis, representing the largest evidence to date to inform P2Y12 inhibitor choice in patients with ACS. Fourteen studies were included, for a total population of 145,019 patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review. A network meta-analysis using a frequentist approach with surface under the cumulative ranking probability calculation was performed. Major adverse cardiovascular events (MACE), all-cause death, myocardial infarction (MI), definite stent thrombosis (ST) and major bleeding at 30-day and 1-year all-cause death and MI were the study endpoints. At 30-day, prasugrel was superior to both clopidogrel and ticagrelor in MACE, all-cause death and definite ST endpoints. Both prasugrel and ticagrelor were superior to clopidogrel in MI endpoint. Ticagrelor also reduced all-cause death compared with clopidogrel. Ticagrelor, prasugrel, and clopidogrel resulted equivalent in terms of the safety outcome of 30-day major bleeding. No significant difference was found among clopidogrel, prasugrel, and ticagrelor with respect to 1-year MACE outcome. Both prasugrel and ticagrelor reduced the occurrence of 1-year all-cause death compared with clopidogrel. Prasugrel reduced 1-year MI rate as compared with clopidogrel, while ticagrelor did not. At probability analyses, prasugrel ranked best in all 30-day and 1-year efficacy and safety endpoints. In conclusion, in this network meta-analysis, prasugrel showed the highest efficacy in reducing adverse outcomes in ACS patients and had the highest probability of being the best P2Y12 inhibitor to reduce hard adverse events both at 30-day and 1-year follow-up.

Circulating irisin levels in heart failure with preserved or reduced ejection fraction: A pilot study.

Irisin, a recently discovered myokine, has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in patients with heart failure (HF), both with preserved (HFpEF) or reduced (HFrEF) ejection fraction. We have therefore evaluated the circulating irisin levels in HFpEF and HFrEF patients, correlating them with metabolic parameters and total antioxidant capacity (TAC), as index of oxidative stress. Irisin was significantly higher in HFpEF than in HFrEF patients (7.72 ± 0.76 vs 2.77 ± 0.77 ng/ml, respectively). An inverse correlation between irisin and TAC was found in HFpEF, but not in HFrEF. Conversely, no correlation was present with HOMA index. These data support the hypothesis that a different pathophysiological mechanism is involved in the two HF subtypes, and oxidative stress modulates irisin secretion.

Cardiovascular autonomic nervous system evaluation in Parkinson disease and multiple system atrophy.

BACKGROUND: Autonomic nervous system dysfunction (ANSd) heralds or follows motor symptoms (MS) in Parkinson disease (PD), but may precede years and progress more rapidly in multiple system atrophy (MSA). Cardiac dysautonomia severity correlates with disabling symptoms thus a Cardiac Autonomic Nervous System Evaluation protocol (CANSEp) is useful to assess ANSd in PD and MSA patients. METHODS AND RESULTS: Consecutive patients with PD or MSA were studied. The severity of MS was quantified with UPDR III and Hoehn/Yahr scales. CANSEp consisted of the 5-test Ewing protocol (EP) and Heart Rate Variability analysis (HRVa), in time-domain (TD) and frequency-domain (FD). 36 patients with parkinsonian symptoms (23 PD, 13 MSA) and 40 healthy controls were studied. Parkinsonism was more severe in MSA, comparing UPDR III and Hoehn/Yahr scales (p<0.0001). Higher EP's scores were found in MSA (mean 5.1±1.98) compared to PD (mean 3.5±2) and controls (score 0.25±0.1). TD and FD-HRVa were abnormal in PD and MSA, compared to controls. In PD depression of vagal tone was predominant during sleep, whereas in MSA depression of sympathetic tone prevailed during daily activity. CONCLUSIONS: Whereas its specificity is very high, the sensitivity of the EP was only 43.5% in PD and 76.9% in MSA. HRVa improved diagnosis accuracy in 10 patients, unidentified by the EP alone, with overall sensitivity of 65.2% in PD and 92.3% in MSA. Thus CANSEp provides a better assessment of cardiovascular dysautonomia in parkinsonian syndromes, useful to differentiate PD from MSA and to address clinical and pharmacological management.

Heart rate variability analysis during head-up tilt test predicts nitroglycerine-induced syncope.

OBJECTIVE: The aim of this study was to determine whether or not heart rate variability (HRV) analysis during the first 20 min of head-up tilt testing could predict whether patients will develop syncope after nitroglycerine administration. DESIGN: 64 patients with previous loss of consciousness underwent head-up tilt testing with the Italian protocol, which involves the administration of nitroglycerine after 20 min of tilt. HRV parameters were analysed from 5 min intervals selected during pretest supine rest (phase 1), the first 5 min (phase 2) and the last 5 min (phase 3) of passive 20 min of tilting, prior to the administration of nitroglycerine. Differences in power (ms(2)) of the spectral components between the various phases of tilting were calculated for each patient and expressed as Δ. RESULTS: 20 patients (group 1, 9 women, mean age 43.2±24.5 years) had a syncope during tilt testing after nitroglycerine, while the other 44 (group 2, 24 women, mean age 41±20.5 years) did not. In group 1, the HRV spectral parameters high frequency (HF) and total power (TP) had a significant decrement from phases 2 to 3 (p=0.012 and 0.027, respectively), while in group 2 the average HF and TP values did not change. The Δ of spectral parameters between phases 2 and 3 were able to differentiate between the two groups and to predict syncope after nitroglycerine administration (p<0.05). CONCLUSIONS: HRV analysis within the first 20 min of passive tilting demonstrated that patients with nitroglycerine-induced syncope are characterised by a progressive decrement of parasympathetic activity, which does not occur in patients with a negative response to nitroglycerine. If confirmed on a wider population, HRV analysis could replace nitroglycerine administration and shorten the duration of the tilt test.

Prevalence of virulent Helicobacter pylori strains in patients affected by idiopathic dysrhythmias.

Helicobacter pylori virulent strains have been shown to affect cardiovascular diseases through molecular mimicry mechanisms. Silent autoimmune myocarditis has been hypothesized to be the cause of idiopathic dysrhythmias (IA). The aim of this study is to assess the prevalence of virulent H. pylori strains in patients affected by IA. In this study,54 patients (40 men, mean age 44 ± 17 years) affected by IA and 50 healthy subjects (34 men, mean age 45 ± 9) were evaluated. IA, defined as dysrhythmias with no evidence of other cardiac pathology, were either supraventricular (SVA, 23 patients; mean age 45 ± 15 years) or ventricular (VA, 31 patients; mean age 42 ± 18 years). H. pylori infection and gastrointestinal (GI) symptoms were evaluated. H. pylori strains expressing the cytotoxin-associated gene A (cagA) and the vacuolating-cytotoxin A (vacA) were also assessed through western blot. The prevalence of H. pylori is similar in IA patients and in controls (42 vs. 44%; p > 0.05); H. pylori infection is observed in 48 and 39% of the patients are affected by SVA and VA, respectively. The prevalence of CagA-positive strains is increased in IA patients compared to controls (65 vs. 42%; p < 0.01); similarly, the prevalence of VacA-positive strains is also increased in IA patients (74 vs. 46%; p < 0.006). Excluding belching, infected patients did not show any difference in GI symptoms, when compared to non-infected subjects. From this study it is concluded that there is an epidemiological link between CagA and VacA-positive H. pylori strains in IA patients.

Percutaneous method for single-catheter multiple monophasic action potential recordings during magnetocardiographic mapping in spontaneously breathing rodents.

To test the feasibility of a novel method to combine magnetocardiographic (MCG) estimate of ventricular repolarization (VR) and multiple monophasic action potential (MultiMAP) recording in spontaneously breathing rodents with percutaneous sub-xyphoid epicardial placement of a MCG-compatible amagnetic catheter (AC), ten Wistar rats (WRs) and ten guinea pigs (GPs) were studied. Under fluoroscopic control, the AC was moved until four stable MAPs were recorded (fixed inter-electrode distance of 1.2 mm). 36-channel DC-SQUID (sensitivity 20 fT Hz(-½)) were used for MCG mapping. MAPs, differentially amplified (BW: DC-500 Hz), were digitized at 1 kHz. AC pacing provided local ventricular effective refractory period (VERP) estimate. MAP duration (MAPd) was measured at 50% and 90% levels of repolarization. Simultaneous MCG mapping and MultiMAP recording were successful in all animals. Average MAPd50% and MAPd90% were shorter in WRs than in GPs (26.4 ± 2.9 ms versus 110.6 ± 14.3 ms and 60.7 ± 5.4 ms versus 127.7 ± 15.3 ms, respectively). VERP was 51 ± 4.8 ms in WRs and 108.4 ± 12.9 ms in GPs, respectively. The MAP amplitude was 16.9 ± 4.5 in WRs and 16.2 ± 4.2 in GPs. MAP and MCG parameters of VR were in good agreement. All animals survived the procedure. Two also survived a second invasive study; one was followed up until natural death at 52 months. Percutaneous MultiMAP recording is minimally invasive, usually avoids animal sacrifice, is compatible with simultaneous surface MCG mapping and might be used for experimental validation of MCG VR abnormality, to study the arrhythmogenic potential of new drugs and/or animal models of ventricular arrhythmias.