Clinical Features and Outcomes Among Patients With Refractory Out-of-Hospital Cardiac Arrest and an Initial Shockable Rhythm.

BACKGROUND: Clinical features among patients with refractory out-of-hospital cardiac arrest (OHCA) and initial shockable rhythms of ventricular fibrillation/pulseless ventricular tachycardia are not well-characterized. METHODS: We compared clinical characteristics and coronary angiographic findings between patients with refractory OHCA (incessant ventricular fibrillation/pulseless ventricular tachycardia after ≥3 direct-current shocks) and those without refractory OHCA. RESULTS: Between 2014 and 2018, a total of 204 patients with ventricular fibrillation/pulseless ventricular tachycardia OHCA (median age 62; males 78%) were divided into groups with (36%, 74/204) and without refractory arrest (64%, 130/204). Refractory OHCA patients had longer cardiopulmonary resuscitation (23 versus 15 minutes), more frequently required ≥450 mg amiodarone (34% versus 3.8%), and had cardiogenic shock (80% versus 55%) necessitating higher adrenaline dose (4.0 versus 1.0 mg) and higher rates of mechanical ventilation (92% versus 74%; all P<0.01). Of 167 patients (82%) selected for coronary angiography, 33% (n=55) had refractory OHCA (P=0.035). Significant coronary artery disease (≥1 major vessel with >70% stenosis) was present in >70% of patients. Refractory OHCA patients frequently had acute coronary occlusion (64% versus 47%), especially left circumflex (20% versus 6.4%) and graft vessel (7.3% versus 0.9%; all P<0.05) compared with those without refractory OHCA. Refractory OHCA group had higher in-hospital mortality (45% versus 30%, P=0.036) and greater new requirement for dialysis (18% versus 6.3%, P=0.011). After adjustment, refractory OHCA was associated with over 2-fold higher odds of in-hospital mortality (odds ratio, 2.28 [95% CI, 1.06-4.89]; P=0.034). CONCLUSIONS: Refractory ventricular fibrillation/pulseless ventricular tachycardia OHCA was associated with more intensive resuscitation, higher rates of acute coronary occlusion, and poorer in-hospital outcomes, underscoring the need for future studies in this extreme-risk subgroup.

Effect of Concomitant Cardiac Arrest on Outcomes in Patients With Acute Coronary Syndrome-Related Cardiogenic Shock.

Patients with acute coronary syndrome (ACS)-related cardiogenic shock (CS) with or without concomitant CA may have disparate prognoses. We compared clinical characteristics and outcomes of patients with CS secondary to ACS with and without cardiac arrest (CA). Between 2014 and 2020, 1,573 patients with ACS-related CS with or without CA who underwent percutaneous coronary intervention enrolled in a multicenter Australian registry were analyzed. Primary outcome was 30-day major adverse cardiovascular and cerebrovascular events (MACCE) (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization and stroke). Long-term mortality was obtained through linkage to the National Death Index. Compared with the no-CA group (n = 769, 49%), the CA group (n = 804, 51%) was younger (62 vs 69 years, p <0.001) and had fewer comorbidities. Patients with CA more frequently had ST-elevation myocardial infarction (92% vs 86%), occluded left anterior descending artery (43% vs 33%), and severe preprocedural renal impairment (49% vs 42%) (all p <0.001). CA increased risk of 30-day MACCE by 45% (odds ratio 1.45, 95% confidence interval 1.05 to 2.00, p = 0.024) after adjustment. CA group had higher 30-day MACCE (55% vs 42%, p <0.001) and mortality (52% vs 37%, p <0.001). Three-year survival was lower for CA compared with no-CA patients (43% vs 52%, p <0.001). In Cox regression, CS with CA was associated with a trend toward greater long-term mortality hazard (hazard ratio 1.19, 95% confidence interval 1.00 to 1.41, p = 0.055). In conclusion, concomitant CA among patients with ACS-related CS conferred a particularly heightened short-term risk with a diminishing legacy effect over time for mortality. CS survivors continue to exhibit high sustained long-term mortality hazard regardless of CA status.

Sex differences among patients presenting to hospital with out-of-hospital cardiac arrest and shockable rhythm.

OBJECTIVE: Sex differences in patients presenting with out-of-hospital cardiac arrest (OHCA) and shockable rhythm might be associated with disparities in clinical outcomes. METHODS: We conducted a retrospective cohort study and compared characteristics and short-term outcomes between male and female adult patients who presented with OHCA and shockable rhythm at two large metropolitan health services in Melbourne, Australia between the period of 2014-2018. Logistic regression was used to assess the effect of sex on clinical outcomes. RESULTS: Of 212 patients, 166 (78%) were males and 46 (22%) were females. Both males and females presented with similar rates of ST-elevation myocardial infarction (44% vs 36%, P = 0.29), although males were more likely to have a history of coronary artery disease (32% vs 13%) and a final diagnosis of a cardiac cause for their OHCA (89% vs 72%), both P = 0.01. Rates of coronary angiography (81% vs 71%, P = 0.23) and percutaneous coronary intervention (51% vs 42%, P = 0.37) were comparable among males and females. No differences in rates of in-hospital mortality (38% vs 37%, P = 0.90) and 30-day major adverse cardiac and cerebrovascular events (composite of all-cause mortality, myocardial infarction, coronary revascularization and nonfatal stroke) (39% vs 41%, P = 0.79) were observed between males and females, respectively. Female sex was not associated with worse in-hospital mortality when adjusted for other variables (odds ratio 0.66, 95% confidence interval 0.28-1.60, P = 0.36). CONCLUSION: Among patients presenting with OHCA and a shockable rhythm, baseline sex and sex differences were not associated with disparities in short-term outcomes in contemporary systems of care.

Meta-Analysis on Drug and Device Therapy of New York Heart Association Functional Class IV Heart Failure With Reduced Ejection Fraction.

Heart failure with reduced ejection fraction (HFrEF) is associated with significant morbidity and mortality, particularly in patients with New York Heart Association (NYHA) functional class IV symptoms. Decades of discovery have heralded significant advancements in the pharmacologic management of HFrEF. However, patients with NYHA IV symptoms remain an under-represented population in almost every clinical trial to date, leaving clinicians with limited evidence with which to guide drug treatment decisions in this patient group with severe heart failure. Randomized controlled trials of adult patients with NYHA IV symptoms of HFrEF randomized to current guideline-recommended medical therapy were included in this systematic review and meta-analysis. The outcomes of interest included the rate of all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A total of 39 randomized controlled trials were included. A total of 6 studies examined angiotensin converting enzyme inhibitors, with meta-analyses of 2 demonstrating a reduced risk of all-cause mortality (relative risk (RR) 0.76, 95% confidence interval 0.59 to 0.97, p = 0.03). A total of 11 studies examined ß blockers, with meta-analysis of 6 demonstrating a reduced risk of all-cause mortality (risk ratio 0.74, 95% confidence interval 0.60 to 0.92, p = 0.008). A study examined the mineralocorticoid antagonist spironolactone, reporting a reduced risk of all-cause mortality in the NYHA IV subgroup. A total of 6 studies examined device therapy, demonstrating the benefit of cardiac resynchronization therapy with or without an implantable cardiac defibrillator in reducing hospitalization in the NYHA IV subgroup. Although trial evidence exists for angiotensin converting enzyme inhibitors, ß-blockers, and mineralocorticoid antagonist therapy in the NYHA IV population, the role of angiotensin receptor blockers is unclear. Ivabradine, angiotensin receptor neprilysin inhibitors, and sodium-glucose transport protein 2 inhibitors remain underinvestigated and have not been proved to provide any benefit above standard heart failure therapy in patients with HFrEF and NYHA IV symptoms.

Evaluation of factors associated with selection for coronary angiography and in-hospital mortality among patients presenting with out-of-hospital cardiac arrest without ST-segment elevation.

BACKGROUND: Clinical factors favouring coronary angiography (CA) selection and variables associated with in-hospital mortality among patients presenting with out-of-hospital cardiac arrest (OHCA) without ST-segment elevation (STE) remain unclear. METHODS: We evaluated clinical characteristics associated with CA selection and in-hospital mortality in patients with OHCA, shockable rhythm and no STE. RESULTS: Between 2014 and 2018, 118 patients with OHCA and shockable rhythm without STE (mean age 59; males 75%) were stratified by whether CA was performed. Of 86 (73%) patients undergoing CA, 30 (35%) received percutaneous coronary intervention (PCI). CA patients had shorter return of spontaneous circulation (ROSC) time (17 vs. 25 min) and were more frequently between 50 and 60 years (29% vs. 6.5%), with initial Glasgow Coma Scale (GCS) score >8 (24% vs. 6%) (all p < 0.05). In-hospital mortality was 33% (n = 39) for overall cohort (CA 27% vs. no-CA 50%, p = 0.02). Compared to late CA, early CA ( ≤ 2 h) was not associated with lower in-hospital mortality (32% vs. 34%, p = 0.82). Predictors of in-hospital mortality included longer defibrillation time (odds ratio 3.07, 95% confidence interval 1.44-6.53 per 5-min increase), lower pH (2.02, 1.33-3.09 per 0.1 decrease), hypoalbuminemia (2.02, 1.03-3.95 per 5 g/L decrease), and baseline renal dysfunction (1.33, 1.02-1.72 per 10 ml/min/1.73 m2 decrease), while PCI to lesion (0.11, 0.01-0.79) and bystander defibrillation (0.06, 0.004-0.80) were protective factors (all p < 0.05). CONCLUSIONS: Among patients with OHCA and shockable rhythm without STE, younger age, shorter time to ROSC and GCS >8 were associated with CA selection, while less effective resuscitation, greater burden of comorbidities and absence of treatable coronary lesion were key adverse prognostic predictors.

Impella versus Venoarterial Extracorporeal Membrane Oxygenation for Acute Myocardial Infarction Cardiogenic Shock: A Systematic Review and Meta-Analysis.

OBJECTIVES: Despite an increase in the use of mechanical circulatory support (MCS) devices for acute myocardial infarction cardiogenic shock (AMI-CS), there is currently no randomised data directly comparing the use of Impella and veno-arterial extra-corporeal membrane oxygenation (VA-ECMO). METHODS: Electronic databases of MEDLINE, EMBASE and CENTRAL were systematically searched in November 2021. Studies directly comparing the use of Impella (CP, 2.5 or 5.0) with VA-ECMO for AMI-CS were included. Studies examining other modalities of MCS, or other causes of cardiogenic shock, were excluded. The primary outcome was in-hospital mortality. RESULTS: No randomised trials comparing VA-ECMO to Impella in patients with AMI-CS were identified. Six cohort studies (five retrospective and one prospective) were included for systematic review. All studies, including 7093 patients, were included in meta-analysis. Five studies reported in-hospital mortality, which, when pooled, was 42.4% in the Impella group versus 50.1% in the VA-ECMO group. Impella support for AMI-CS was associated with an 11% relative risk reduction in in-hospital mortality compared to VA-ECMO (risk ratio 0.89; 95% CI 0.83-0.96, I2 0%). Of the six studies, three studies also adjusted outcome measures via propensity-score matching with reported reductions in in-hospital mortality with Impella compared to VA-ECMO (risk ratio 0.72; 95% CI 0.59-0.86, I2 35%). Pooled analysis of five studies with 6- or 12-month mortality data reported a 14% risk reduction with Impella over the medium-to-long-term (risk ratio 0.86; 95% CI 0.76-0.97, I2 0%). CONCLUSIONS: There is no high-level evidence comparing VA-ECMO and Impella in AMI-CS. In available observation studies, MCS with Impella was associated with a reduced risk of in-hospital and medium-term mortality as compared to VA-ECMO.

Determinants of Undertaking Coronary Angiography and Adverse Prognostic Predictors Among Patients Presenting With Out-of-Hospital Cardiac Arrest and a Shockable Rhythm.

Characteristics of patients presenting with out-of-hospital cardiac arrest (OHCA) selected for coronary angiography (CA) and factors predicting in-hospital mortality remain unclear. We assessed clinical characteristics associated with undertaking CA in patients presenting with OHCA and shockable rhythm (CA group). Predictors of in-hospital mortality were evaluated with multivariable analysis. Of 1,552 patients presenting with cardiac arrest between 2014 and 2018 to 2 health services in Victoria, Australia, 213 patients with OHCA and shockable rhythm were stratified according to CA status. The CA group had shorter cardiopulmonary resuscitation duration (17 vs 25 minutes) and time to return of spontaneous circulation (17 vs 26 minutes) but higher proportion of ST-elevation on electrocardiogram (48% vs 24%) (all p <0.01). In-hospital mortality was 38% (n = 81) for the overall cohort, 32% (n = 54) in the CA group, and 61% (n = 27) in the no-CA group. Predictors of in-hospital mortality included non-selection for CA (odds ratio 4.5, 95% confidence interval 1.5 to 14), adrenaline support (3.9, 1.3 to 12), arrest at home (2.7, 1.1 to 6.6), longer time to defibrillation (2.5, 1.5 to 4.2 per 5-minute increase), lower blood pH (2.1, 1.4 to 3.2 per 0.1 decrease), lower albumin (2.0, 1.2 to 3.3 per 5 g/L decrease), higher Acute Physiology and Chronic Health Evaluation II score (1.7, 1.0 to 3.0 per 5-point increase), and advanced age (1.4, 1.0 to 2.0 per 10-year increase) (all p ≤0.05). In conclusion, non-selection for CA, concomitant cardiogenic shock requiring inotropic support, poor initial resuscitation (arrest at home, longer time to defibrillation and lower pH), greater burden of co-morbidities (higher Acute Physiology and Chronic Health Evaluation II score and lower albumin), and advanced age were key adverse prognostic indicators among patients with OHCA and shockable rhythm.

Adverse 30-Day Clinical Outcomes and Long-Term Mortality Among Patients With Preprocedural Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: Approximately 5-10% of patients presenting for percutaneous coronary intervention (PCI) have concurrent atrial fibrillation (AF). To what extent AF portends adverse long-term outcomes in these patients remains to be defined. METHODS: We analysed data from the multicentre Melbourne Interventional Group Registry from 2014-2018. Patients were identified as being in AF or sinus rhythm (SR) at the commencement of PCI. The primary endpoint was long-term mortality, obtained via linkage with the National Death Index. RESULTS: 13,286 procedures were included, with 800 (6.0%) patients in AF and 12,486 (94.0%) in SR. Compared to SR, patients with AF were older (72.9±10.9 vs 64.1±12.0 p<0.001) and more likely to have comorbidities including diabetes mellitus (31.3% vs 25.0% p<0.001), hypertension (74.4% vs 65.1% p<0.001) and moderate to severe left ventricular systolic dysfunction (36.6% vs 19.5% p<0.001). Atrial fibrillation was associated with an increased risk of in-hospital mortality (11.0% vs 2.5% p<0.001) and MACE (composite of all-cause mortality, myocardial infarction, or target vessel revascularisation) (11.9% vs 4.2% p<0.001). In-hospital major bleeding was more common in the AF group (3.1% vs 1.0% p<0.001). On Cox proportional hazards modelling, AF was an independent predictor of long-term mortality (adjusted HR 1.38 95% CI 1.11-1.72 p<0.004) at a mean follow-up of 2.3±1.5 years. CONCLUSIONS: Preprocedural AF is common among patients presenting for PCI. Preprocedural AF is associated with high-rates of comorbid illnesses and portends higher risk of short- and long-term outcomes including mortality underscoring the need for careful evaluation of its risks prior to PCI.

Vasoplegia Following Orthotopic Heart Transplantation: Prevalence, Predictors and Clinical Outcomes.

BACKGROUND: Patients undergoing heart transplant are at high risk for postoperative vasoplegia. Despite its frequency and association with poor clinical outcomes, there remains no consensus definition for vasoplegia, and the predisposing risk factors for vasoplegia remain unclear. Accordingly, the aim of this study was to evaluate the prevalence, predictors, and clinical outcomes associated with vasoplegia in a contemporary cohort of patients undergoing heart transplantation. METHODS: This was a retrospective cohort study of patients undergoing heart transplantation from January 2015 to December 2019. A binary definition of vasoplegia of a cardiac index of 2.5 L/min/m2 or greater and requirement for norepinephrine (≥5 µg/min), epinephrine (≥4 µg/min), or vasopressin (≥1 unit/h) to maintain a mean arterial blood pressure of 65 mm Hg, for 6 consecutive hours during the first 48 hours postoperatively, was used in determining prevalence. Given the relatively low threshold for the binary definition of vasoplegia, patients were divided into tertiles based on their cumulative vasopressor requirement in the 48 hours following transplant. Outcomes included all-cause mortality, intubation time, intensive care unit length of stay, and length of total hospitalization. RESULTS: After exclusion of patients with primary cardiogenic shock, major bleeding, or overt sepsis, data were collected on 95 eligible patients. By binary definition, vasoplegia incidence was 66.3%. We separately stratified by actual vasopressor requirement tertile (high, intermediate, low). Stratified by tertile, patients with vasoplegia were older (52.7 ± 10.2 vs 46.8 ± 12.7 vs 44.4 ± 11.3 years, P = .02), with higher rates of chronic kidney disease (18.8% vs 32.3% vs 3.1%, P = .01) and were more likely to have been transplanted from left ventricular assist device support (n = 42) (62.5% vs 32.3% vs 37.5%, P = .03). Cardiopulmonary bypass time was prolonged in those that developed vasoplegia (155 min [interquartile range 135-193] vs 131 min [interquartile range 117-152] vs 116 min [interquartile range 102-155], P = .003). Intubation time and length of intensive care unit and hospital stay were significantly increased in those that developed vasoplegia; however, this difference did not translate to a significant increase in all-cause mortality at 30 days or 1 year. CONCLUSIONS: Vasoplegia occurs at a high rate after heart transplantation. Older age, chronic kidney disease, mechanical circulatory support, and prolonged bypass time are all associated with vasoplegia; however, this study did not demonstrate an associated increase in all-cause mortality LAY SUMMARY: Patients undergoing heart transplantation are at high risk of vasoplegia, a condition defined by low blood pressure despite normal heart function. We found that vasoplegia was common after heart transplant, occurring in 60%-70% of patients after heart transplant after excluding those with other causes for low blood pressure. Factors implicated included age, poor kidney function, prolonged cardiopulmonary bypass time and preoperative left ventricular assist device support. We found no increased risk of death in patients with vasoplegia despite longer lengths of stay in intensive care and in hospital.

Relation of Timing of Percutaneous Coronary Intervention on Outcomes in Patients With Non-ST Segment Elevation Myocardial Infarction.

International guidelines suggest revascularization within 24 hours in non-ST segment elevation myocardial infarction (NSTEMI). Within a large population cohort study, we aimed to explore clinical practice regarding timing targets for percutaneous coronary intervention (PCI) in NSTEMI. The Victorian Cardiac Outcomes Registry was established in 2013 as a state-wide clinical quality registry, pooling data from public and private PCI capable centers. Data were collected on 11,852 PCIs performed for NSTEMI from 2014 to 2018. Patients were divided into 3 groups by time of symptom onset to PCI (<24 hours; 24 to 72 hours; >72 hours). We performed multivariable logistic regression analysis conditional on several baseline covariates in investigating the impact of timing of PCI in NSTEMI on clinical outcomes. Patients who underwent PCI within 24 hours represented 18.4% (n = 2,178); 24 to 72 hours 45.8% (n = 5,434); >72 hours 35.8% (n = 4,240). Patients waiting longer for PCI were older (62.6 ± 12.2 vs 64.8 ± 12.6 vs 67.0 ± 12.7, p <0.001), more likely to be female (23.1% vs 24.2% vs 26.4%, p = 0.007), and have diabetes (18.6% vs 21.1% vs 27.1%, p <0.001). Multivariate logistic regression found that as compared with PCI <24 hours, PCI 24 to 72 hours and PCI >72 hours of symptom onset were associated with a decreased risk of 30-day mortality (odds ratio 0.55; 95% confidence interval 0.35 to 0.86, p = 0.008 and odds ratio 0.64; 95% confidence interval 0.35 to 1.01, p = 0.053, respectively). There was no significant difference in 30-day mortality between groups following exclusion of patients presenting with cardiogenic shock or out of hospital cardiac arrest requiring intubation. In conclusion, many registry patients undergo PCI outside the 24-hour window following NSTEMI. This delay is at odds with current guideline recommendations but does not appear to be associated with an increased mortality risk.