The impact of sex, body mass index and chronic kidney disease on outcomes following percutaneous coronary intervention.

OBJECTIVE: This study sought to evaluate 1) the relationship between body mass index (BMI), chronic kidney disease (CKD) and bleeding complications in patients undergoing percutaneous coronary intervention (PCI); and 2) whether CKD modified the effect of BMI on major bleeding and major adverse cardiac and cerebrovascular events (MACCE). BACKGROUND: The interaction of CKD, sex and BMI in patients undergoing PCI is unclear. METHODS: Between 2010 and 2018, a total of 31,116 patients underwent PCI at six New York metropolitan area hospitals. Bleeding complications were classified by the Bleeding Academic Research Consortium (BARC). Major bleeding was defined as BARC≥3. MACCE was the composite of in-hospital death; myocardial infarction; cerebrovascular events and major bleeding complications. Interaction on multiplicative scales was assessed adjusting for other factors. A three-way multiplicative interaction between BMI, CKD and sex were considered and evaluated for both endpoints of primary interest (BARC≥3 and MACCE). RESULTS: Patients with BARC≥3 bleeding were older (p < 0.0001) and more likely female (p < 0.0001). A 3-way interaction existed between sex, BMI, and CKD on BARC≥3 (p = 0.02). Specifically, the effect of CKD status on odds of BARC≥3 depended on BMI group among males, whereas BMI did modify the relationship between CKD and BARC≥3 among females; after stratification by sex, a significant interaction between BMI and CKD was present in females (p = 0.03) but not in males (p = 0.43). Among females without CKD, normal BMI patients had the greatest odds of BARC≥3 compared to obese or overweight females. Contrasted to females without CKD, among females with CKD there was no significant increased odds of BARC≥3 in normal BMI patients compared to obese or overweight females. However, overweight females with CKD had a significantly increased odds of BARC≥3 compared to obese females with CKD. Furthermore, obese females with CKD had significantly greater BARC≥3 odds compared to obese females without CKD. Similarly, overweight females with CKD had an increased odds of BARC≥3 compared to overweight females without CKD. No significant interactions were found for the odds of MACCE. CONCLUSION: In patients undergoing PCI, there was evidence of a significant and complex 3-way interaction between BMI, CKD and sex for major bleeding events. The predicted probability of major bleeding was greater for females than for male patients, and for both sexes, greater among those with CKD, but BMI group influences these probabilities. Obese females with kidney disease had the lowest incidence of bleeding complications when compared with overweight or normal weight female patients undergoing PCI. This interaction was not seen in the male group or for MACCE. Furthermore, age, cardiogenic shock, STEMI and use of IABP/Impella were each independently associated with odds of major bleeding (among both males and females) and MACCE.

Percutaneous coronary intervention with Impella support with and without intra-aortic balloon in cardiogenic shock patients.

OBJECTIVE: To assess the clinical characteristics and in-hospital bleeding complications and major adverse cardiac and cerebrovascular events (MACCE) associated with the use of Impella alone or the combination of an intra-aortic balloon pump (IABP) with Impella in cardiogenic shock (CS) patients undergoing percutaneous coronary intervention (PCI). METHODS: All CS patients who underwent PCI and were treated with an Impella mechanical circulatory support (MCS) device were identified. Patients were divided into two groups: having MCS support with Impella alone or with both, IABP and Impella simultaneously (dual MCS group). Bleeding complications were classified by a modified Bleeding Academic Research Consortium (BARC) classification. Major bleeding was defined as BARC≥3 bleeding. MACCE was the composite of in-hospital death, myocardial infarction, cerebrovascular events and major bleeding complications. RESULTS: Between 2010 and 2018 a total of 101 patients were treated at six tertiary care New York hospitals with either Impella (n = 61) or dual MCS with Impella and IABP (n = 40). Clinical characteristics were similar for both groups. Dual MCS patients presented more often with a STEMI (77.5 % vs. 45.9 %, p = 0.002) and had left main coronary artery intervention (20.3 % vs. 8.6 %, p = 0.03). Major bleeding complications (69.4 % vs. 74.1 %, p = 0.62) and MACCE rates (80.6 % vs. 79.3 %, p = 0.88) were very high but similar in both groups, however access site bleeding complications were lower in patients treated with dual MCS. In-hospital mortality was 29.5 % for the Impella group and 25.0 % for the dual MCS group (p = 062). Access site bleeding complications were lower in in patients treated with dual MCS (5.0 % vs. 24.6 %, p = 0.01). CONCLUSION: In CS patients undergoing PCI with either the Impella device alone or with Impella and IABP, major bleeding complications and MACCE rates were high but not significantly different between the two groups. In hospital mortality was relatively low in both MCS groups despite the high-risk characteristics of these patients. Future studies should assess the risks and benefits of the simultaneous use of these two MCS in CS patients undergoing PCI.

1-Year Outcomes of Blinded Physiological Assessment of Residual Ischemia After Successful PCI: DEFINE PCI Trial.

OBJECTIVES: The aim of this study was to identify the post-percutaneous coronary intervention (PCI) target value of instantaneous wave-free ratio (iFR) that would best discriminate clinical events at 1 year in the DEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) study. BACKGROUND: The impact of residual ischemia detected by iFR post-PCI on clinical and symptom-related outcomes is unknown. METHODS: Blinded iFR pull back was performed after successful stent implantation in 500 patients. The primary endpoint was the rate of residual ischemia, defined as iFR ≤0.89, after operator-assessed angiographically successful PCI. Secondary endpoints included clinical events at 1 year and change in Seattle Angina Questionnaire angina frequency (SAQ-AF) score during follow-up. RESULTS: As reported, 24.0% of patients had residual ischemia (iFR ≤0.89) after successful PCI, with 81.6% of cases attributable to angiographically inapparent focal lesions. Post-PCI iFR ≥0.95 (present in 182 cases [39%]) was associated with a significant reduction in the composite of cardiac death, spontaneous myocardial infarction, or clinically driven target vessel revascularization compared with post-PCI iFR <0.95 (1.8% vs 5.7%; P = 0.04). Baseline SAQ-AF score was 73.3 ± 22.8. For highly symptomatic patients (baseline SAQ-AF score ≤60), SAQ-AF score increased by ≥10 points more frequently in patients with versus without post-PCI iFR ≥0.95 (100.0% vs 88.5%; P = 0.01). CONCLUSIONS: In DEFINE PCI, despite angiographically successful PCI, highly symptomatic patients at baseline without residual ischemia by post-PCI iFR had greater reductions in anginal symptoms at 1 year compared with patients with residual ischemia. Achieving post-PCI iFR ≥0.95 was also associated with improved 1-year event-free survival. (Physiologic Assessment of Coronary Stenosis Following PCI [DEFINE PCI]; NCT03084367).

Clinical outcomes according to lesion complexity in high bleeding risk patients treated with 1-month dual antiplatelet therapy following PCI: Analysis from the Onyx ONE clear study.

OBJECTIVES: To compare clinical outcomes in high bleeding risk (HBR) patients with and without complex percutaneous coronary intervention (PCI) treated with Resolute Onyx zotarolimus-eluting stents (ZES) after 1-month dual antiplatelet therapy (DAPT). BACKGROUND: PCI with 1-month DAPT has been demonstrated to be safe in HBR patients treated with Resolute Onyx ZES. Whether these outcomes are consistent in patients with complex lesions is uncertain. METHODS: Among HBR patients who were event-free 1 month after PCI with ZES and treated thereafter with single antiplatelet therapy (SAPT), the clinical outcomes between 1 month and 1 year were compared after complex PCI (3 vessels treated, ≥ 3 lesions treated, total stent length > 60 mm, bifurcation with ≥ 2 stents implanted, atherectomy, or left main, surgical bypass graft or chronic total occlusion PCI) versus noncomplex PCI. Propensity score adjustment was performed to adjust for baseline differences among complex and noncomplex patients. RESULTS: Complex patients (N = 401, 26.6% of total) had a higher prevalence of hyperlipidemia, diabetes mellitus and previous myocardial infarction (MI). Between 1 month and 1 year, rates of MI (7.1% vs. 4.0%, p = 0.02) and cardiac death/MI (9.3% vs. 6.1%, p = 0.04) were higher among complex versus noncomplex patients, although stent thrombosis rates were similar. After adjustment for baseline characteristics, differences in outcomes were no longer significant between groups. CONCLUSIONS: Higher rates of ischemic outcomes in complex PCI patients were largely explained by baseline clinical differences, rather than lesion complexity, among HBR patients treated with 1-month DAPT following PCI with Resolute Onyx ZES.

Aortic Arch Thrombus and Pulmonary Embolism in a COVID-19 Patient.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with endothelial inflammation and a hypercoagulable state resulting in both venous and arterial thromboembolic complications. We present a case of COVID-19-associated aortic thrombus in an otherwise healthy patient. CASE REPORT: A 53-year-old woman with no past medical history presented with a 10-day history of dyspnea, fever, and cough. Her pulse oximetry on room air was 84%. She tested positive for severe acute respiratory syndrome coronavirus 2 infection, and chest radiography revealed moderate patchy bilateral airspace opacities. Serology markers for cytokine storm were significantly elevated, with a serum D-dimer level of 8180 ng/mL (normal < 230 ng/mL). Computed tomography of the chest with i.v. contrast was positive for bilateral ground-glass opacities, scattered filling defects within the bilateral segmental and subsegmental pulmonary arteries, and a large thrombus was present at the aortic arch. The patient was admitted to the intensive care unit and successfully treated with unfractionated heparin, alteplase 50 mg, and argatroban 2 µg/kg/min. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Mural aortic thrombus is a rare but serious cause of distal embolism and is typically discovered during an evaluation of cryptogenic arterial embolization to the viscera or extremities. Patients with suspected hypercoagulable states, such as that encountered with COVID-19, should be screened for thromboembolism, and when identified, aggressively anticoagulated.

Usefulness of Elevated Troponin to Predict Death in Patients With COVID-19 and Myocardial Injury.

Elevations in troponin levels have been shown to predict mortality in patients with coronavirus disease 2019 (COVID-19). The role of inflammation in myocardial injury remains unclear. We sought to determine the association of elevated troponin with mortality in a large, ethnically diverse population of patients hospitalized with COVID-19, and to determine the association of elevated inflammatory markers with increased troponin levels. We reviewed all patients admitted at our health system with COVID-19 from March 1 to April 27, 2020, who had a troponin assessment within 48 hours of admission. We used logistic regression to calculate odds ratios (ORs) for mortality during hospitalization, controlling for demographics, co-morbidities, and markers of inflammation. Of 11,159 patients hospitalized with COVID-19, 6,247 had a troponin assessment within 48 hours. Of these, 4,426 (71%) patients had normal, 919 (15%) had mildly elevated, and 902 (14%) had severely elevated troponin. Acute phase and inflammatory markers were significantly elevated in patients with mildly and severely elevated troponin compared with normal troponin. Patients with elevated troponin had significantly increased odds of death for mildly elevated compared with normal troponin (adjusted OR, 2.06; 95% confidence interval, 1.68 to 2.53; p < 0.001) and for severely elevated compared with normal troponin (OR, 4.51; 95% confidence interval, 3.66 to 5.54; p < 0.001) independently of elevation in inflammatory markers. In conclusion, patients hospitalized with COVID-19 and elevated troponin had markedly increased mortality compared with patients with normal troponin levels. This risk was independent of cardiovascular co-morbidities and elevated markers of inflammation.

Bradyarrhythmias in patients with COVID-19: Marker of poor prognosis?

BACKGROUND: Despite descriptions of various cardiovascular manifestations in patients with coronavirus disease 2019 (COVID-19), there is a paucity of reports of new onset bradyarrhythmias, and the clinical implications of these events are unknown. METHODS: Seven patients presented with or developed severe bradyarrhythmias requiring pacing support during the course of their COVID-19 illness over a 6-week period of peak COVID-19 incidence. A retrospective review of their presentations and clinical course was performed. RESULTS: Symptomatic high-degree heart block was present on initial presentation in three of seven patients (43%), and four patients developed sinus arrest or paroxysmal high-degree atrioventricular block. No patients in this series demonstrated left ventricular systolic dysfunction or acute cardiac injury, whereas all patients had elevated inflammatory markers. In some patients, bradyarrhythmias occurred prior to the onset of respiratory symptoms. Death from complications of COVID-19 infection occurred in 57% (4/7) patients during the initial hospitalization and in 71% (5/7) patients within 3 months of presentation. CONCLUSIONS: Despite management of bradycardia with temporary (3/7) or permanent leadless pacemakers (4/7), there was a high rate of short-term morbidity and death due to complications of COVID-19. The association between new-onset bradyarrhythmias and poor outcomes may influence management strategies for acutely ill patients with COVID-19.

Sex-Related Differences in Early- and Long-Term Mortality After Transcatheter and Surgical Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

BACKGROUND: Observational data suggest that early- and long-term outcomes of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differ significantly between men and women, but have demonstrated conflicting results. This study sought to examine early- and long-term mortality with TAVR and SAVR in women versus men. METHODS: Electronic search was performed until February 2018 for studies reporting sex-specific mortality following TAVR or isolated SAVR. Data were pooled using random-effects models. Outcomes included rates of early mortality (in hospital or 30 days) and long term (1 year or longer). RESULTS: With 35 studies, a total of 80,928 patients were included in our systematic review and meta-analysis, including 40,861 men and 40,067 women. Pooled analyses suggested considerable sex-related differences in longterm mortality following TAVR and SAVR. Following SAVR, women had higher long-term mortality (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.16-1.56; P<.001) and a trend toward higher early mortality (OR, 1.69; 95% CI, 0.97-2.97; P=.07) compared to men. Following TAVR, women had lower long-term mortality (OR, 0.78; 95% CI, 0.71-0.86; P<.001) and no difference in early mortality (OR, 1.09; 95% CI, 0.96-1.23; P=.17) compared to men. CONCLUSIONS: In this systematic review and meta-analysis, women had higher long-term mortality and a trend toward higher early mortality compared to men following SAVR. Following TAVR, women had lower long-term mortality and no difference in early mortality compared with men.

Correction to: Patient-specific simulation of transcatheter aortic valve replacement: impact of deployment options on paravalvular leakage.

This is to inform that the original article was published without the "Conflict of Interest" statement.

Blinded Physiological Assessment of Residual Ischemia After Successful Angiographic Percutaneous Coronary Intervention: The DEFINE PCI Study.

OBJECTIVES: This study sought to evaluate the incidence and causes of an abnormal instantaneous wave-free ratio (iFR) after angiographically successful percutaneous coronary intervention (PCI). BACKGROUND: Impaired coronary physiology as assessed by fractional flow reserve is present in some patients after PCI and is prognostically relevant. METHODS: DEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) was a multicenter, prospective, observational study in which a blinded iFR pull back was performed after angiographically successful PCI in 562 vessels in 500 patients. Inclusion criteria were angina with either multivessel or multilesion coronary artery disease with an abnormal baseline iFR. The primary endpoint of the study was the rate of residual ischemia after operator-assessed angiographically successful PCI, defined as an iFR <0.90. The causes of impaired iFR were categorized as stent related, untreated proximal or distal focal stenosis, or diffuse atherosclerosis. RESULTS: An average of 1.1 vessels per patient had abnormal baseline iFRs, with a mean value of 0.69 ± 0.22, which improved to 0.93 ± 0.07 post-PCI. Residual ischemia after angiographically successful PCI was present in 112 patients (24.0%), with a mean iFR in that population of 0.84 ± 0.06 (range 0.60 to 0.89). Among patients with impaired post-PCI iFRs, 81.6% had untreated focal stenoses that were angiographically inapparent, and 18.4% had diffuse disease. Among the focal lesions, 38.4% were located within the stent segment, while 31.5% were proximal and 30.1% were distal to the stent. Post-PCI vessel angiographic diameter stenosis was not a predictor of impaired post-procedural iFR. CONCLUSIONS: Blinded post-PCI physiological assessment detected residual ischemia in nearly 1 in 4 patients after coronary stenting despite an operator-determined angiographically successful result. Most cases of residual ischemia were due to inapparent focal lesions potentially amenable to treatment with additional PCI. (Physiologic Assessment of Coronary Stenosis Following PCI [DEFINE PCI]; NCT03084367).

Simultaneous thoracic aortic endovascular graft and transfemoral transcatheter aortic valve replacement in a patient with a descending aortic thrombus.

Severe descending thoracic and abdominal aortic pathology can deter consideration of transfemoral (TF) access for transcatheter aortic valve replacement (TAVR) in adults with severe symptomatic aortic stenosis (AS) and may lead to utilization of alternative access sites. We report a case of an 88-year-old frail woman with severe symptomatic AS referred for TAVR with demonstration of a large thrombus in the descending thoracic aorta immediately distal to the left subclavian artery. Given concerns of thrombus embolization with femoral advancement of the transcatheter valve, coverage with a thoracic aortic endograft was planned immediately prior to the TAVR.

Patient-specific simulation of transcatheter aortic valve replacement: impact of deployment options on paravalvular leakage.

Transcatheter aortic valve replacement (TAVR) has emerged as an effective alternative to conventional surgical valve replacement in high-risk patients afflicted by severe aortic stenosis. Despite newer-generation devices enhancements, post-procedural complications such as paravalvular leakage (PVL) and related thromboembolic events have been hindering TAVR expansion into lower-risk patients. Computational methods can be used to build and simulate patient-specific deployment of transcatheter aortic valves (TAVs) and help predict the occurrence and degree of PVL. In this study finite element analysis and computational fluid dynamics were used to investigate the influence of procedural parameters on post-deployment hemodynamics on three retrospective clinical cases affected by PVL. Specifically, TAV implantation depth and balloon inflation volume effects on stent anchorage, degree of paravalvular regurgitation and thrombogenic potential were analyzed for cases in which Edwards SAPIEN and Medtronic CoreValve were employed. CFD results were in good agreement with corresponding echocardiography data measured in patients in terms of the PVL jets locations and overall PVL degree. Furthermore, parametric analyses demonstrated that positioning and balloon over-expansion may have a direct impact on the post-deployment TAVR performance, achieving as high as 47% in PVL volume reduction. While the model predicted very well clinical data, further validation on a larger cohort of patients is needed to verify the level of the model's predictions in various patient-specific conditions. This study demonstrated that rigorous and realistic patient-specific numerical models could potentially serve as a valuable tool to assist physicians in pre-operative TAVR planning and TAV selection to ultimately reduce the risk of clinical complications.

Impact of prior revascularization on the outcomes of patients presenting with ST-elevation myocardial infarction and cardiogenic shock.

BACKGROUND: Patient presenting with ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) have extremely high mortality rates. OBJECTIVES: We sought to assess the impact of prior revascularization by either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) on the in-hospital and 12-month outcomes and compare them with revascularization-naïve patients. METHODS AND RESULTS: Between 1/2010 and 5/2017, a total of 241 consecutive patients were admitted to our institution with STEMI and CS as defined by New York State Percutaneous Coronary Interventions Reporting System (PCIRS) and underwent primary PCI. Baseline clinical, angiographic and procedural characteristics, as well as in-hospital outcomes were prospectively collected among all patients undergoing primary PCI as part of the New York State PCIRS data collection. Patients with a history of prior bypass graft surgery were older and had a history of heart failure, hypertension, dyslipidemia, and diabetes. The left anterior descending coronary artery was usually the culprit vessel in post PCI and revascularization naïve patients, whereas it was a vein graft in patients with a prior history of surgical bypass. In-hospital mortality rates were different in the three groups and there was no significant difference in major adverse cardiac and cerebrovascular events rates among the three groups (p = 0.87). Notably, revascularization-naïve patients had higher rates of major bleeding complications (p = 0.006). By multivariable analysis, only age (OR 1.03; CI = 1.0-1.06), a prior history of congestive heart failure (OR 4.36, CI = 1.04-18.38) and dyslipidemia (OR 0.32 CI = 0.15-0.64) were independent predictors of 12-month mortality. Prior revascularization had no impact on rates of stroke, death or MACCE. CONCLUSIONS: Patients with acute STEMI and CS had similar in-hospital and one year mortality, stroke or major adverse cardiac and cerebrovascular events rates irrespective of their prior revascularization status.

Left ventricular end diastolic pressure and contrast-induced acute kidney injury in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Left ventricular end-diastolic pressure (LVEDP) reflects ventricular performance and volume status. We sought to analyze the relationship between LVEDP and the incidence of contrast-induced acute kidney injury (AKI) in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). METHODS: Between January 2006 and December 2008, a total of 254 patients presenting with an acute coronary syndrome had the LVEDP assessed prior to the intervention. Contrast-induced AKI was defined as an increase in serum creatinine ≥25% from baseline or an absolute increase of >0.5 mg/dL from baseline. Patients were divided into three groups according to baseline LVEDP (<12 mmHg, 12-20 mmHg and > 20 mmHg). Baseline clinical, angiographic and procedural characteristics, as well as serum creatinine and estimated glomerular filtration rate (eGFR) at baseline and at 24, 48 and 72 h were retrospectively collected. RESULTS: Baseline clinical characteristics were similar in all three groups with the exception of lower left ventricular ejection fraction in patients with elevated LVEDP (p = 0.02). Among the 17 patients with an LVEDP < 12 mmHg, only one (5.9%) developed AKI; among the 82 patients with an LVEDP = 12-20 mmHg, 15 (18.3%) developed AKI; and among the 155 patients with an LVEDP > 20 mmHg, only 22 developed AKI (13.6%). There was no correlation between LVEDP and the change in GFR at 24 h and at 48 h. Further comparison between the group of patients that developed contrast induced AKI versus those that did not, showed a that there was a significantly lower baseline left ventricular ejection fraction (LVEF) among patients that developed contrast induced AKI compared to those that did not (41.4% vs. 48.3%, p = 0.045, respectively). CONCLUSIONS: In patients with acute coronary syndrome undergoing PCI, baseline LVEDP was not associated with contrast-induced AKI. However patients with reduced ejection fraction seemed to be at a higher risk of developing AKI. More studies are needed to assess the relationship between LVEDP, LVEF and the risk of developing contrast induced AKI.

Realistic Vascular Replicator for TAVR Procedures.

Transcatheter aortic valve replacement (TAVR) is an over-the-wire procedure for treatment of severe aortic stenosis (AS). TAVR valves are conventionally tested using simplified left heart simulators (LHS). While those provide baseline performance reliably, their aortic root geometries are far from the anatomical in situ configuration, often overestimating the valves' performance. We report on a novel benchtop patient-specific arterial replicator designed for testing TAVR and training interventional cardiologists in the procedure. The Replicator is an accurate model of the human upper body vasculature for training physicians in percutaneous interventions. It comprises of fully-automated Windkessel mechanism to recreate physiological flow conditions. Calcified aortic valve models were fabricated and incorporated into the Replicator, then tested for performing TAVR procedure by an experienced cardiologist using the Inovare valve. EOA, pressures, and angiograms were monitored pre- and post-TAVR. A St. Jude mechanical valve was tested as a reference that is less affected by the AS anatomy. Results in the Replicator of both valves were compared to the performance in a commercial ISO-compliant LHS. The AS anatomy in the Replicator resulted in a significant decrease of the TAVR valve performance relative to the simplified LHS, with EOA and transvalvular pressures comparable to clinical data. Minor change was seen in the mechanical valve performance. The Replicator showed to be an effective platform for TAVR testing. Unlike a simplified geometric anatomy LHS, it conservatively provides clinically-relevant outcomes and complement it. The Replicator can be most valuable for testing new valves under challenging patient anatomies, physicians training, and procedural planning.