Incidence, Outcomes, and Opportunity for Left Ventricular Assist Device Weaning for Myocardial Recovery.

BACKGROUND: Myocardial recovery occurs in patients with advanced heart failure on left ventricular assist device (LVAD) support, but there is the premise that it is rare with uncertain results. OBJECTIVES: The goal of this study was to investigate the incidence and consequence of LVAD explant after myocardial recovery. METHODS: Using the United Network for Organ Sharing registry, LVAD implants in the United States between 2005 and 2020 were tracked until death, transplantation, or explant for myocardial recovery. The cohort undergoing explant was followed up for heart failure relapse (defined as relisting followed by delisting due to death, being too ill, or transplantation; or second durable LVAD implant). RESULTS: Of 15,728 LVAD implants, 126 patients underwent explant for recovery, which only occurred in 55 (38%) of 145 implanting centers. The crude cumulative incidence was 0.7% at 2 years, whereas the incidence reached 4.7% among designated centers in the selected young nonischemic cohort. Of 126 explanted patients, 76 (60%) were subsequently delisted for sustained recovery. Heart failure relapsing had a relatively higher hazard in the early phase, with a 30-day incidence of 6% (7 of 126) but tapered following with the freedom rate of 72.5% at 4 years. CONCLUSIONS: In the United States, LVAD explant for myocardial recovery was underutilized, leading to a very low incidence at the national level despite a realistic rate being achieved in designated centers for selected patients. With follow-up extending up to 4 years after explant, more than one-half were successfully removed and stayed off the waitlist, and approximately 70% were free from heart failure relapse events.

Cardiac Catheterization Laboratory Management of the Comatose Adult Patient With an Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association.

Out-of-hospital cardiac arrest is a leading cause of death, accounting for ≈50% of all cardiovascular deaths. The prognosis of such individuals is poor, with <10% surviving to hospital discharge. Survival with a favorable neurologic outcome is highest among individuals who present with a witnessed shockable rhythm, received bystander cardiopulmonary resuscitation, achieve return of spontaneous circulation within 15 minutes of arrest, and have evidence of ST-segment elevation on initial ECG after return of spontaneous circulation. The cardiac catheterization laboratory plays an important role in the coordinated Chain of Survival for patients with out-of-hospital cardiac arrest. The catheterization laboratory can be used to provide diagnostic, therapeutic, and resuscitative support after sudden cardiac arrest from many different cardiac causes, but it has a unique importance in the treatment of cardiac arrest resulting from underlying coronary artery disease. Over the past few years, numerous trials have clarified the role of the cardiac catheterization laboratory in the management of resuscitated patients or those with ongoing cardiac arrest. This scientific statement provides an update on the contemporary approach to managing resuscitated patients or those with ongoing cardiac arrest.

The Evaluation and Management of Coronary Artery Disease in the Lung Transplant Patient.

Lung transplantation can greatly improve quality of life and extend survival in those with end-stage lung disease. In order to derive the maximal benefit from such a procedure, patients must be carefully selected and be otherwise healthy enough to survive a high-risk surgery and sometimes prolonged immunosuppressive therapy following surgery. Patients therefore must be critically assessed prior to being listed for transplantation with close attention paid towards assessment of cardiovascular health and operative risk. One of the biggest dictators of this is coronary artery disease. In this review article, we discuss the assessment and management of coronary artery disease in the potential lung transplant candidate.

Left Ventricular Unloading With Impella Versus IABP in Patients With VA-ECMO: A Systematic Review and Meta-Analysis.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use for circulatory support in cardiogenic shock results in increased left ventricular (LV) afterload. The use of concomitant Impella or intra-aortic balloon pump (IABP) have been proposed as adjunct devices for LV unloading. The authors sought to compare head-to-head efficacy and safety outcomes between the 2 LV unloading strategies. We conducted a search of Medline, EMBASE, and Cochrane databases to identify studies comparing the use of Impella to IABP in patients on VA-ECMO. The primary outcome of interest was in-hospital mortality. The secondary outcomes included transition to durable LV assist devices/cardiac transplantation, stroke, limb ischemia, need for continuous renal replacement therapy, major bleeding, and hemolysis. Pooled risk ratios (RRs) with 95% confidence interval and heterogeneity statistic I2 were calculated using a random-effects model. A total of 7 observational studies with 698 patients were included. Patients on VA-ECMO unloaded with Impella vs IABP had similar risk of short-term all-cause mortality, defined as either 30-day or in-hospital mortality- 60.8% vs 64.9% (RR 0.93 [0.71 to 1.21], I2 = 71%). No significant difference was observed in transition to durable LV assist devices/cardiac transplantation, continuous renal replacement therapy initiation, stroke, or limb ischemia between the 2 strategies. However, the use of VA-ECMO with Impella was associated with increased risk of major bleeding (57.2% vs 39.7%) (RR 1.66 [1.12 to 2.44], I2 = 82%) and hemolysis (31% vs 7%) (RR 4.61 [1.24 to 17.17], I2 = 66%) compared with VA-ECMO, along with IABP. In conclusion, in patients requiring VA-ECMO for circulatory support, the concomitant use of Impella or IABP had comparable short-term mortality. However, Impella use was associated with increased risk of major bleeding and hemolysis.

Outcomes of Simultaneous Heart and Kidney Transplantation.

BACKGROUND: Simultaneous heart-kidney transplantation has been increasingly performed in end-stage heart failure patients with concurrent kidney dysfunction despite limited evidence supporting its indications and utility. OBJECTIVES: The purpose of this study was to investigate the effects and utility of simultaneously implanted kidney allografts with various degrees of kidney dysfunction during heart transplantation. METHODS: Using the United Network for Organ Sharing registry, long-term mortality was compared in recipients with kidney dysfunction who underwent heart-kidney transplantation (n = 1,124) vs isolated heart transplantation (n = 12,415) in the United States between 2005 and 2018. In heart-kidney recipients, contralateral kidney recipients were compared for allograft loss. Multivariable Cox regression was used for risk adjustment. RESULTS: Long-term mortality was lower among heart-kidney recipients than among heart-alone recipients when recipients were on dialysis (26.7% vs 38.6% at 5 years; HR: 0.72; 95% CI: 0.58-0.89) or had a glomerular filtration rate (GFR) of <30 mL/min/1.73 m2 (19.3% vs 32.4%; HR: 0.62; 95% CI: 0.46-0.82) and GFR of 30 to 45 mL/min/1.73 m2 (16.2% vs 24.3%; HR: 0.68; 95% CI: 0.48-0.97) but not in GFR of 45 to 60 mL/min/1.73 m2. Interaction analysis showed that the mortality benefit of heart-kidney transplantation continued up to GFR 40 mL/min/1.73 m2. The incidence of kidney allograft loss was higher among heart-kidney recipients than among contralateral kidney recipients (14.7% vs 4.5% at 1 year; HR: 1.7; 95% CI: 1.4-2.1). CONCLUSIONS: Heart-kidney transplantation relative to heart transplantation alone provided superior survival for dialysis-dependent recipients and non-dialysis-dependent recipients up to a GFR of approximately 40 mL/min/1.73 m2 but at the cost of almost twice the risk of kidney allograft loss than contralateral kidney allograft recipients.

Ticagrelor or prasugrel versus clopidogrel in patients undergoing percutaneous coronary intervention for chronic coronary syndromes.

BACKGROUND: Potent P2Y12 inhibitors such as ticagrelor and prasugrel are superior to clopidogrel in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). Whether this benefit extends to a patient population with chronic coronary syndromes (CCS) is unclear. AIMS: We sought to compare the safety and efficacy of prasugrel and ticagrelor versus clopidogrel in patients undergoing PCI for CCS. METHODS: Consecutive patients undergoing PCI for CCS at a tertiary centre between 2014 and 2019 who were discharged on prasugrel or ticagrelor were compared with those on clopidogrel. The primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularisation at 1 year. RESULTS: Overall, 11,508 patients were included in the study (ticagrelor/prasugrel n=2,860 [24.9%], clopidogrel n=8,648 [75.1%]) with an increasing frequency of potent P2Y12 inhibitor use over the study period (ptrend<0.001). Clopidogrel was used more frequently in patients with multimorbid risk factors, whereas anatomical or procedural complexity was associated with ticagrelor/prasugrel use (left main PCI, bifurcation PCI, number of lesions, rotational atherectomy). No difference in the incidence of death or MI was noted across the groups (ticagrelor/prasugrel vs clopidogrel: 2.7% vs 3.1%, adjusted hazard ratio [adjHR] 0.86, 95% confidence interval [CI]: 0.62-1.17; p=0.33) or secondary outcomes including bleeding (adjHR 0.75, 95% CI: 0.46-1.21; p=0.23) on propensity score stratification analysis. Additionally, no difference in the primary outcome was observed across subgroups, including those undergoing complex PCI. CONCLUSIONS: Ticagrelor and prasugrel are increasingly used in patients with CCS undergoing PCI with similar 1-year efficacy and safety when compared to clopidogrel. Whether use of these agents can be beneficial in patients undergoing PCI for CCS with a high thrombotic and low bleeding risk warrants further study.

High-Risk Pulmonary Embolism During Labor: JACC Patient Care Pathways.

While in labor, a 37-year-old woman developed acute dyspnea, hypoxemia, and tachycardia. Transthoracic echocardiography demonstrated severe right ventricular dilation and dysfunction, raising the suspicion of acute pulmonary embolism. The patient indeed had bilateral pulmonary embolism, necessitating percutaneous thrombectomy. Her course was complicated by another saddle pulmonary embolus, heparin-induced thrombocytopenia, and COVID-19 infection. This clinical case illustrates the importance of prompt diagnosis of acute pulmonary embolism in a peripartum female patient, the multidisciplinary approach of management, and how to approach clinical complications such as heparin-induced thrombocytopenia. Furthermore, long-term management in acute pulmonary embolism is presented.

High-Risk Pulmonary Embolism During Labor: JACC Patient Care Pathways.

While in labor, a 37-year-old woman developed acute dyspnea, hypoxemia, and tachycardia. Transthoracic echocardiography demonstrated severe right ventricular dilation and dysfunction, raising the suspicion of acute pulmonary embolism. The patient indeed had bilateral pulmonary embolism, necessitating percutaneous thrombectomy. Her course was complicated by another saddle pulmonary embolus, heparin-induced thrombocytopenia, and COVID-19 infection. This clinical case illustrates the importance of prompt diagnosis of acute pulmonary embolism in a peripartum female patient, the multidisciplinary approach of management, and how to approach clinical complications such as heparin-induced thrombocytopenia. Furthermore, long-term management in acute pulmonary embolism is presented.

Temporary mechanical circulatory support devices: practical considerations for all stakeholders.

Originally intended for life-saving salvage therapy, the use of temporary mechanical circulatory support (MCS) devices has become increasingly widespread in a variety of clinical settings in the contemporary era. Their use as a short-term, prophylactic support vehicle has expanded to include procedures in the catheterization laboratory, electrophysiology suite, operating room and intensive care unit. Accordingly, MCS device design and technology continue to develop at a rapid pace. In this Review, we describe the functionality, indications, management and complications associated with temporary MCS, together with scenario-specific utilization, goal-directed development and bioengineering of future devices. We address various considerations for the use of temporary MCS devices in both prophylactic and rescue scenarios, with input from stakeholders from various cardiovascular specialties, including interventional and heart failure cardiology, electrophysiology, cardiothoracic anaesthesiology, critical care and cardiac surgery.

Ticagrelor vs Prasugrel in a Contemporary Real-World Cohort Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Potent P2Y12 agents such as ticagrelor and prasugrel are increasingly utilized across the clinical spectrum of patients undergoing percutaneous coronary intervention (PCI). There is a paucity of data supporting their use in a patient population inclusive of both acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. OBJECTIVES: The authors compared the efficacy and safety of ticagrelor and prasugrel in a real-world contemporary PCI cohort. METHODS: Consecutive patients undergoing PCI between 2014 and 2019 discharged on either prasugrel or ticagrelor were included from the prospectively collected institutional PCI registry. Primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularization at 1 year. RESULTS: Overall, 3,858 patients were included in the study (ticagrelor: n = 2,771; prasugrel: n = 1,087), and a majority (48.4%) underwent PCI in the context of CCS. Patients prescribed ticagrelor were more likely to be female, have a history of cerebrovascular disease, and have ACS presentation, while those receiving prasugrel were more likely to be White with a higher prevalence of prior revascularization. No difference in the risk of death or MI was noted across the groups (ticagrelor vs prasugrel: 3.3% vs 3.1%; HR: 0.88; 95% CI: 0.54-1.43; P = 0.59). Rates of target vessel revascularization were significantly lower in the ticagrelor cohort (9.3% vs 14.0%; adjusted HR: 0.71; 95% CI: 0.55-0.91; P = 0.007) with no differences in stroke or bleeding. The results were consistent in patients with CCS (HR: 0.84; 95% CI: 0.46-1.54) and ACS (HR: 1.18; 95% CI: 0.46-1.54), without evidence of interaction (P = 0.37), and confirmed across multivariable adjustment and propensity score stratification analysis. CONCLUSIONS: In this contemporary patient population undergoing PCI, prasugrel and ticagrelor were associated with similar 1-year efficacy and safety.

Coronary Dissection and Right Heart Failure Salvaged by PCI With Percutaneous Intraluminal Microaxial RV-Assist Support.

Right heart failure is a dreaded sequelae of proximal right coronary artery occlusion that can complicate an angiogram or percutaneous coronary intervention. This case illustrates the use of a percutaneous intraluminal microaxial right ventricular assist device for high-risk percutaneous coronary intervention of an ostial right coronary artery dissection in refractory right heart failure. (Level of Difficulty: Advanced.).

Characterization of Myocardial Injury in Patients With COVID-19.

BACKGROUND: Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data. OBJECTIVES: This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19. METHODS: We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. RESULTS: A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities. CONCLUSIONS: Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

COVID-19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis.

Patients with severe COVID-19 disease have been characterized as having the acute respiratory distress syndrome (ARDS). Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Many patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated d-dimers and higher rates of venous thromboembolism. We present four cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock, with evidence of markedly elevated dead-space ventilation who received tPA. All showed post treatment immediate improvements in gas exchange and/or hemodynamics. We suspect that severe COVID-19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction. Treatment for COVID-19 pneumonia may warrant anticoagulation for milder cases and thrombolysis for more severe disease.

COVID-19 Critical Illness Pathophysiology Driven by Diffuse Pulmonary Thrombi and Pulmonary Endothelial Dysfunction Responsive to Thrombolysis.

Patients with severe COVID-19 disease have been characterized as having the acute respiratory distress syndrome (ARDS). Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated D-dimers and higher rates of venous thromboembolism. We present five cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock, with evidence of markedly elevated dead-space ventilation who received tPA. All showed post treatment immediate improvements in gas exchange and/or hemodynamics. We suspect that severe COVID-19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction. Treatment for COVID-19 pneumonia may warrant anticoagulation for milder cases and thrombolysis for more severe disease.

Predictors of Left Ventricular Ejection Fraction Improvement After Primary Stenting in ST-Segment Elevation Myocardial Infarction (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial).

The predictors of improvement in left ventricular ejection fraction (LVEF) after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) are poorly understood. We sought to determine the prevalence and clinical and angiographic predictors of LVEF improvement after primary PCI in STEMI. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction trial, 3,602 patients presenting with STEMI were randomized to heparin + a glycoprotein IIb/IIIa inhibitor versus bivalirudin. Routine 13-month angiographic follow-up was performed in a prespecified substudy of 656 stented patients. The median [25%, 75%] change in LVEF from baseline to 13 months was +2.4% [-5.9%, 11.8%]; LVEF increased or remained unchanged in 379 patients (57.8%; median Δ +9.8% [4.3%, 16.4%]) and fell in 277 patients (42.2%; median Δ -7.0% [-11.8%, -3.6%]). Independent predictors of LVEF improvement were female gender (p = 0.002), lower baseline LVEF (p <0.0001), Thrombolysis in Myocardial Infarction 3 flow after PCI (p = 0.03), shorter lesion length (p = 0.04), and lower post-PCI peak MB isoenzyme of creatine kinase (p <0.0001). In conclusion, in the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction trial, although LVEF improved during follow-up after primary PCI in more than half of patients, left ventricular function worsened over time in a substantial proportion, the occurrence of which may be predicted by clinical, angiographic, and laboratory variables.

Incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction: the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction Trial.

BACKGROUND: Reinfarction after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction has negative consequences. Little is known about reinfarction after drug-eluting stents and bivalirudin anticoagulation. We, therefore, sought to determine the incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in the contemporary era. METHODS AND RESULTS: Outcomes were assessed in 3202 patients undergoing stent implantation for ST-segment-elevation myocardial infarction in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Independent predictors of reinfarction and mortality were identified by Cox proportional hazards modeling. The cumulative incidence of reinfarction was 1.8% at 30 days, 4.0% at 1 year, and 6.9% at 3 years. Definite stent thrombosis was responsible for 76.3% of reinfarctions occurring within 30 days and 52.0% of all reinfarctions within 3 years. Independent predictors of reinfarction were current smoking, Killip class ≥2, baseline thrombocytosis, multivessel disease, symptom onset-to-balloon time, and total stent length. Randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting versus bare metal stents were not significant predictors of reinfarction. Reinfarction was a powerful independent predictor of subsequent cardiac mortality (hazard ratio [95% confidence interval]=7.65 [4.47-13.09]; P<0.0001) and all-cause mortality (hazard ratio [95% confidence interval]=2.88 [1.74-4.78]; P<0.0001). CONCLUSIONS: Despite advances in pharmacotherapy and stents, reinfarction after primary percutaneous coronary intervention is not infrequent, in the contemporary era is most often attributable to stent thrombosis, and is strongly associated with subsequent cardiac and all-cause mortality. Further enhancements in drugs and devices to prevent reinfarction are needed to improve outcomes in high-risk patients with ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium.

Cardiac experimental biology and translational research would benefit from an in vitro surrogate for human heart muscle. This study investigated structural and functional properties and interventional responses of human engineered cardiac tissues (hECTs) compared to human myocardium. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs, >90% troponin-positive) were mixed with collagen and cultured on force-sensing elastomer devices. hECTs resembled trabecular muscle and beat spontaneously (1.18 ± 0.48 Hz). Microstructural features and mRNA expression of cardiac-specific genes (α-MHC, SERCA2a, and ACTC1) were comparable to human myocardium. Optical mapping revealed cardiac refractoriness with loss of 1:1 capture above 3 Hz, and cycle length dependence of the action potential duration, recapitulating key features of cardiac electrophysiology. hECTs reconstituted the Frank-Starling mechanism, generating an average maximum twitch stress of 660 µN/mm(2) at Lmax, approaching values in newborn human myocardium. Dose-response curves followed exponential pharmacodynamics models for calcium chloride (EC50 1.8 mM) and verapamil (IC50 0.61 µM); isoproterenol elicited a positive chronotropic but negligible inotropic response, suggesting sarcoplasmic reticulum immaturity. hECTs were amenable to gene transfer, demonstrated by successful transduction with Ad.GFP. Such 3-D hECTs recapitulate an early developmental stage of human myocardium and promise to offer an alternative preclinical model for cardiology research.

Low-density lipoprotein levels in patients with acute heart failure.

Statins do not appear to have a significant benefit in heart failure (HF) as they do in coronary artery disease (CAD). Significant evidence exists that low serum cholesterol levels may be harmful in HF. This study sought to determine the optimal low-density lipoprotein (LDL) level in patients hospitalized with acute HF. Patients were included if they presented to the hospital with acute HF and had a lipid panel drawn during admission. The primary outcome was all-cause mortality, and secondary outcomes were rates of major cardiovascular (CV) events, left ventricular assist device (LVAD) implantation, and orthotopic heart transplantation (OHT). A total of 2428 patients were followed for a mean of 2.9±2.2 years. For the entire cohort, when compared with those with LDL levels >130 mg/dL, all-cause mortality was higher in those with LDL levels <71 mg/dL (hazard ratio, 1.68; 95% confidence interval, 1.31-2.167; P<.01). Results were similar when analyzing patients with LVEF ≤40%, HF of ischemic etiology only, and in statin users. The rates of CV events, LVAD implantation, or OHT in any comparison did not differ. Low LDL levels (<71 mg/dL), similar to low total cholesterol levels, were associated with a poorer prognosis and higher overall mortality in patients with HF, regardless of etiology and systolic function.