Clinical Outcomes of Renal Transplant Recipients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Clinical outcomes of patients with renal transplant (RT) undergoing percutaneous coronary intervention (PCI) remain poorly elucidated. METHOD: Between 2014 and 2021, data were analysed for the following three groups of patients undergoing PCI enrolled in a multicentre Australian registry: (1) RT recipients (n=226), (2) patients on dialysis (n=992), and (3) chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR], 30‒60 mL/min per 1.73 m2) without previous RT (n=15,534). Primary outcome was 30-day major adverse cardiac and cerebrovascular events (MACCEs)-composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, and stroke. RESULTS: RT recipients were younger than dialysis and patients with CKD (61±10 vs 68±12 vs 78±8.2 years, p<0.001). Patients with RT less frequently had severe left ventricular dysfunction compared with dialysis and CKD groups (6.7% vs 14% and 8.5%); however more, often presented with acute coronary syndrome (58% vs 52% and 48%), especially STEMI (all p<0.001). Patients with RT and CKD had lower rates of 30-day MACCE (4.4% and 6.8% vs 11.6%, p<0.001) than the dialysis group. Three-year survival was similar between RT and CKD groups, however was lower in the dialysis group (80% and 83% vs 60%, p<0.001). After adjustment, dialysis was an independent predictor of 30-day MACCE (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.44‒2.50, p<0.001), however RT was not (OR 0.91, CI 0.42‒1.96, p=0.802). Both RT (hazard ratio [HR] 2.07, CI 1.46‒2.95, p<0.001) and dialysis (HR 1.35, CI 1.02‒1.80, p=0.036) heightened the hazard of long-term mortality. CONCLUSIONS: RT recipients have more favourable clinical outcomes following PCI compared with patients on dialysis. However, despite having similar short-term outcomes to patients with CKD, the hazard of long-term mortality is significantly greater for RT recipients.

Novel therapeutic targets and emerging treatments for atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide. Even with excellent control of low-density lipoprotein cholesterol (LDL-C) levels, adverse cardiovascular events remain a significant clinical problem worldwide, including among those without any traditional ASCVD risk factors. It is necessary to identify novel sources of residual risk and to develop targeted strategies that address them. Lipoprotein(a) has become increasingly recognized as a new cardiovascular risk determinant. Large-scale clinical trials have also signalled the potential additive cardiovascular benefits of decreasing triglycerides beyond lowering LDL-C levels. Since CANTOS (Anti-inflammatory Therapy with Canakinumab for Atherosclerotic Disease) demonstrated that antibodies against interleukin-1ß may decrease recurrent cardiovascular events in secondary prevention, various anti-inflammatory medications used for rheumatic conditions and new monoclonal antibody therapeutics have undergone rigorous evaluation. These data build towards a paradigm shift in secondary ASCVD prevention, underscoring the value of targeting multiple biological pathways in the management of both lipid levels and systemic inflammation. Evolving knowledge of the immune system, and the gut microbiota may result in opportunities for modifying previously unrecognized sources of residual inflammatory risk. This review provides an overview of novel therapeutic targets for ASCVD and emerging treatments with a focus on mechanisms, efficacy, and safety.

T-Remodeling of the Pulmonary Artery Bifurcation for Pulmonary Artery Origin Stenosis.

BACKGROUND: Various surgical techniques are utilized for reconstructing hypoplastic pulmonary arteries (PAs) in patients with conotruncal anomalies and at times, may be susceptible to restenosis and reoperation. We reviewed our experience with a simple technique of T-shaped remodeling of the PA bifurcation. METHODS: Between 2005 and 2019, 31 patients underwent T-remodeling of central PAs by a single cardiac surgeon. The PA bifurcation was opened cranially, and the opening was augmented with an oval-shaped patch effectively transforming the V-shaped bifurcation into a T-shaped bifurcation. Both origins of the PAs were enlarged, even in the instance of single PA origin stenosis. RESULTS: Median age at time of T-remodeling was 17 months (range: 7 weeks to 14 years). The following cardiac morphologies were observed: tetralogy of Fallot (n = 12, 39%), pulmonary atresia with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (n = 8, 26%), truncus arteriosus (n = 6, 19%), pulmonary atresia with VSD (n = 3, 9.7%), and transposition of the great arteries (n = 2, 6.5%). Thirteen patients (42%) had previous central shunt, and eight patients (26%) had previous modified Blalock-Taussig shunt. There were no operative mortalities. Immediately after T-remodeling, echocardiographic estimates of right ventricle to PA gradient decreased from 42 [interquartile range 28-58] mm Hg to 20 [12-36] mm Hg (P = .03). Freedom from reoperation on the PA bifurcation for the entire cohort was 100% at one year, 88% (95% CI 68%-96%) at five years and 82% (57%-93%) at ten years. CONCLUSIONS: T-remodeling for PA origin stenosis is a safe procedure with excellent freedom from reoperation that is easily reproducible and applicable to patients with all cardiac morphologies.

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.

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.

Adverse Impact of Peri-Procedural Stroke in Patients Who Underwent Percutaneous Coronary Intervention.

Peri-procedural stroke (PPS) is an important complication in patients who underwent percutaneous coronary intervention (PCI). The extent to which PPS impacts mortality and outcomes remains to be defined. Consecutive patients who underwent PCI enrolled in the Victorian Cardiac Outcomes Registry (2014 to 2018) were categorized into PPS and no PPS groups. The primary outcome was 30-day major adverse cardiovascular events (MACEs) (composite of mortality, myocardial infarction, stent thrombosis, and unplanned revascularization). Of 50,300 patients, PPS occurred in 0.26% patients (n = 133) (71% ischemic, and 29% hemorrhagic etiology). Patients who developed PPS were older (69 vs 66 years) compared with patients with no PPS, and more likely to have pre-existing heart failure (59% vs 29%), chronic kidney disease (33% vs 20%), and previous cerebrovascular disease (13% vs 3.6%), p <0.01. Among those with PPS, there was a higher frequency of presentation with ST-elevation myocardial infarction (49% vs 18%) and out-of-hospital cardiac arrest (14% vs 2.2%), PCI by way of femoral access (59% vs 46%), and adjunctive thrombus aspiration (12% vs 3.6%), all p = <0.001. PPS was associated with incident 30-day MACE (odds ratio [OR] 2.97, 95% confidence intervals [CIs] 1.86 to 4.74, p <0.001) after multivariable adjustment. Utilizing inverse probability of treatment weighting analysis, PPS remained predictive of 30-day MACE (OR 1.91, 95% CI 1.31 to 2.80, p = 0.001) driven by higher 30-day mortality (OR 2.0, 95% CI 1.35 to 2.96, p = 0.001). In conclusion, in this large, multi-center registry, the incidence of PPS was low; however, its clinical sequelae were significant, with a twofold increased risk of 30-day MACE and all-cause death.

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.

Fate of Patients With Single Ventricles Who Do Not Undergo the Fontan Procedure.

BACKGROUND: The Fontan procedure, the last of a series of palliative operations for patients born with single ventricles, is associated with a significant late burden of complications. There are other strategies for patients who are suboptimal candidates for Fontan completion; however, the long-term outcomes of these different surgical options have not been clearly elucidated. We performed a systematic literature review to establish the current role of other treatment approaches besides the Fontan procedure. METHODS: The MEDLINE and Embase databases were systematically searched for articles describing the long-term outcomes of patients with single ventricles who have not received the Fontan procedure. RESULTS: A total of 36 articles met all inclusion criteria. There is a scarcity of contemporary data on the non-Fontan cohort. Historical studies provided a significant contribution. CONCLUSIONS: Long-term survival of unoperated patients with single ventricles is possible under the rare conditions of having balanced hemodynamics. As many as half of patients may survive on only a systemic-to-pulmonary artery shunt or bidirectional cavopulmonary shunt for more than 20 years with reasonable functional status. In patients with a failing single ventricle, the bidirectional cavopulmonary shunt is an excellent bridge to heart transplantation and may provide better posttransplant survival than patients with a Fontan circulation. Currently, the Fontan procedure continues to be the best definitive palliation for patients born with single ventricle lesions. However, for those with borderline indications, other strategies should be carefully considered.