Revising the Maximal Contrast Dose for Predicting Acute Kidney Injury following Coronary Intervention.

INTRODUCTION: The maximal allowable contrast dose (MACD = 5 × body weight/serum creatinine) is an empiric equation that has been used and validated in several studies to mitigate the risk of contrast-induced acute kidney injury (CI-AKI). However, coefficient 5 (referred to as factor K) was empirically devised and never disputed. The aim of this study was to refine the MACD equation for the prediction of CI-AKI following percutaneous coronary interventions (PCIs). METHODS: This is a single-center, retrospective cohort study of adults undergoing PCI. Electronic medical records were reviewed to identify patients who underwent PCI between 2010 and 2019, derived from the National Cardiovascular Data Registry Cath-PCI registry for our hospital. Factor K (defined as contrast volume × serum creatinine/body weight) was calculated for every patient. A receiver operating characteristic (ROC) curve was constructed, and the Youden index was used to identify the optimal cut-off value for factor K in predicting severe (stages 2-3) CI-AKI. RESULTS: Of the 3,506 patients undergoing PCI, 255 (7.2%) developed CI-AKI, and 68 (26.7%) of the 255 experienced severe AKI. Factor K predicted all-stage CI-AKI (area under the ROC curve 0.649; 95% CI 0.611, 0.686) but had better performance for predicting severe (stages 2-3) AKI (0.736; 95% CI 0.674, 0.800). The optimal cut-off value for factor K in predicting severe CI-AKI was 2.5, with a corresponding sensitivity of 68.7% and specificity of 70.5%. On subgroup analyses, optimal cut-off values for factor K for high-risk groups were not significantly different from those of low-risk groups. CONCLUSION: Our study indicates that factor K in the MACD equation is an independent risk factor for the development of severe CI-AKI, with an optimal cut-off value of 2.5. If our findings are validated, the MACD equation should be revised to incorporate the coefficient of 2.5 instead of 5.

Validation and comparison of non-hyperemic pressure reserve to fractional flow reserve for assessment of coronary artery stenosis: A real world study.

BACKGROUND: The visual interpretation of an angiographic stenosis may not always reflect the physiological significance of a lesion. Fractional Flow Reserve (FFR) is a reliable index to assess the significance of a lesion during hyperemia. However, there are pitfalls that can lead to significant misinterpretation and adverse events. OBJECTIVE: This study sought to evaluate the accuracy and predictability of the non-hyperaemic pressure ratio (NHPR) without hyperemic stimuli, compared to hyperemic FFR. METHODS: We conducted a retrospective, multicenter study of 700 patients who underwent a pressure recording during coronary angiography using NHPR and FFR measurements. Receiver operator characteristic (ROC) curve was constructed. NHPR sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy test were calculated. The most accurate NHPR cutoff was determined. RESULTS: Of the 700 procedures, 449 cases were included. By ROC analysis, the optimal cut-point for NHPR was 0.93 to predict an FFR of ≤0.80 with an overall diagnostic accuracy of 78.84%. The sensitivity of this NHPR cutoff was 85.06%, specificity of 75.59%, PPV of 64.53% and a NPV of 90.65%. There was an overall accuracy of about 80% for predicting non-hyperemic index (FFR < 0.80) using a cutoff of NHPR ≤ 0.93. CONCLUSIONS: The use of NHPR can be considered in certain clinical scenarios where adenosine is contraindicated or there are other challenges; with the knowledge that hyperemia might be necessary if there is any high clinical suspicion as it still remains the reference standard for diagnostic certainty.

Routine Angiographic Follow-Up After Coronary Artery Disease Revascularization: Is Seeing Believing?

PURPOSE OF THE REVIEW: Coronary artery disease is a major cause of mortality and morbidity in the world, and PCI and CABG account for over a million procedures performed annually in the USA. The goal of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is to achieve complete revascularization (CR) if at all possible. However, restenosis and stent thrombosis (ST) remain the Achilles heel of contemporary PCI with restenosis rates between 10 and 30% with bare metal stents to 5-15% after drug-eluting stents and ST rates of around 0.8 vs 1.2%, respectively. Routine angiography after revascularization seems theoretically attractive as this may allow intervention before clinical events occur. In this manuscript, we review the literature regarding routine angiography after PCI or CABG and its outcomes. RECENT FINDINGS: According to the 2016 update from the American Heart Association (AHA), 15.5 million people above the age of 20 have coronary heart disease (CHD) in the USA. The prevalence of CHD is now almost similar in both men and women, and one American suffers from a myocardial infarction (MI) every 42 s. Recent data from randomized clinical trials and observational studies does not support the use of routine coronary angiography after revascularization in asymptomatic patients. There are some studies which show that routine angiography may have a role in left main or complex coronary interventions; however, these findings are exploratory and were not seen in randomized trials. After reviewing the data on routine angiography after coronary revascularization, we came to the conclusion that current data does not support the use of routine angiography for asymptomatic patients. However, there is a lack of randomized controlled trial in this field with only one recent trial reporting negative outcomes.

Native coronary artery thrombosis in the setting of heparin-induced thrombocytopenia: a case report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin therapy. Its pathogenesis includes thrombotic events that can rarely affect the coronary arteries. CASE SUMMARY: We report a 67-year-old woman who presented with extensive lower extremities deep venous thrombosis. After being treated with heparin, she developed an ST-elevation myocardial infarction secondary to an acute thrombus formation. The patient's platelets dropped within 6 days from the procedure and her heparin-PF4 IgG antibody and serotonin release assay were positive confirming the diagnosis of HIT. DISCUSSION: Prothrombotic states, such as HIT, are associated with increased risk for coronary thrombosis and ischaemia. Heparin-induced thrombocytopenia can cause coronary complications usually in previously disrupted coronary vessels and bypass grafts. Here, we demonstrate that spontaneous thrombosis can occur in a previously untreated native coronary artery in a patient with HIT.

Transcatheter aortic valve replacement in unicuspid aortic valve stenosis.

Unicuspid aortic valve (UAV) offers unique challenges to transcatheter aortic valve replacement (TAVR), due to asymmetric expansion and apposition of the prosthesis during implantation. Although TAVR in bicuspid is now a well described experience, TAVR in unicuspid valve has not yet been described. A challenging case is described with TAVR in UAV using a Edwards Sapiens prosthesis via transapical approach. © 2016 Wiley Periodicals, Inc.

Refractory Hypotension as an Initial Presentation of Bilateral Subclavian Artery Stenosis.

Bilateral subclavian stenosis is a rare clinical condition. An interbrachial pressure difference of 15 mm Hg can raise suspicion for unilateral subclavian artery stenosis, but the diagnosis of bilateral subclavian artery stenosis can be challenging. We present a case of a 75-year-old woman who presented with refractory hypotension after surgery. Initial vitals revealed blood pressure in the 60s/50s mm Hg in both arms. Cardiopulmonary examination was remarkable for diminished pulses in all 4 extremities and audible carotid bruits. She continued to be hypotensive despite aggressive fluid resuscitation. Troponin T peaked at 0.24 ng/mL (reference < 0.04), and an echocardiogram revealed a reduction in ejection fraction (37% from 50%). Left and right heart catheterization demonstrated normal filling pressures and cardiac output. During the procedure, however, it was noted that the patient's central blood pressure was 70-80 mm Hg higher than cuff pressures obtained in either arm. Selective angiography revealed 90% left subclavian ostial stenosis as well as 70% stenosis of the right subclavian artery.

Cardiovascular risks associated with low dose ionizing particle radiation.

Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1)H; 0.5 Gy, 1 GeV) and iron ion ((56)Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56)Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56)Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

Therapeutic non-toxic doses of TNF induce significant regression in TNFR2-p75 knockdown Lewis lung carcinoma tumor implants.

Tumor necrosis factor-alpha (TNF) binds to two receptors: TNFR1/p55-cytotoxic and TNFR2/p75-pro-survival. We have shown that tumor growth in p75 knockout (KO) mice was decreased more than 2-fold in Lewis lung carcinoma (LLCs). We hypothesized that selective blocking of TNFR2/p75 LLCs may sensitize them to TNF-induced apoptosis and affect the tumor growth. We implanted intact and p75 knockdown (KD)-LLCs (>90%, using shRNA) into wild type (WT) mice flanks. On day 8 post-inoculation, recombinant murine (rm) TNF-α (12.5 ng/gr of body weight) or saline was injected twice daily for 6 days. Tumor volumes (tV) were measured daily and tumor weights (tW) on day 15, when study was terminated due to large tumors in LLC+TNF group. Tubular bones, spleens and peripheral blood (PB) were examined to determine possible TNF toxicity. There was no significant difference in tV or tW between LLC minus (-) TNF and p75KD/LLC-TNF tumors. Compared to 3 control groups, p75KD/LLC+TNF showed >2-5-fold decreases in tV (p<0.001) and tW (p<0.0001). There was no difference in tV or tW end of study vs. before injections in p75KD/LLC+TNF group. In 3 other groups tV and tW were increased 2.7-4.5-fold (p<0.01, p<0.0002 and p<0.0001). Pathological examination revealed that 1/3 of p75KD/LLC+rmTNF tumors were 100% necrotic, the remaining revealed 40-60% necrosis. No toxicity was detected in bone marrow, spleen and peripheral blood. We concluded that blocking TNFR2/p75 in LLCs combined with intra-tumoral rmTNF injections inhibit LLC tumor growth. This could represent a novel and effective therapy against lung neoplasms and a new paradigm in cancer therapeutics.

The association between experience and proficiency with robotic-enhanced coronary intervention-insights from the PRECISE multi-center study.

OBJECTIVES: The PRECISE multi-center study demonstrated the safety and feasibility of robotic-enhanced coronary intervention (PCI). We studied the learning curve associated with the robotic PCI approach. METHODS: The CorPath 200 robotic system was used to perform clinically indicated PCI. The first 3 cases performed by each interventional cardiologist were considered early-experience cases and subsequent procedures were regarded as advanced-experience cases. We compared procedure efficiency, patient radiation exposure, and clinical outcomes in early and advanced-experience cases. RESULTS: A total of 164 robotic-enhanced PCI procedures were performed, with 60 early-experience cases. Advanced-experience cases were associated with shorter procedure duration (51.3 ± 25.5 min vs. 42.2 ± 16.4 min, P = 0.008) and fluoroscopy time (12.9 ± 7.8 min vs. 10.1 ± 4.8 min, 0.009) as compared to early-experience cases. CONCLUSIONS: After performing 3 cases, interventionalists were able to complete robotic-enhanced PCI faster, with reduced radiation, and without compromising safety. The steep learning curve highlights the easy adoption of remote-control robotic technology for PCI.

Nonemergency PCI at hospitals with or without on-site cardiac surgery.

BACKGROUND: Emergency surgery has become a rare event after percutaneous coronary intervention (PCI). Whether having cardiac-surgery services available on-site is essential for ensuring the best possible outcomes during and after PCI remains uncertain. METHODS: We enrolled patients with indications for nonemergency PCI who presented at hospitals in Massachusetts without on-site cardiac surgery and randomly assigned these patients, in a 3:1 ratio, to undergo PCI at that hospital or at a partner hospital that had cardiac surgery services available. A total of 10 hospitals without on-site cardiac surgery and 7 with on-site cardiac surgery participated. The coprimary end points were the rates of major adverse cardiac events--a composite of death, myocardial infarction, repeat revascularization, or stroke--at 30 days (safety end point) and at 12 months (effectiveness end point). The primary end points were analyzed according to the intention-to-treat principle and were tested with the use of multiplicative noninferiority margins of 1.5 (for safety) and 1.3 (for effectiveness). RESULTS: A total of 3691 patients were randomly assigned to undergo PCI at a hospital without on-site cardiac surgery (2774 patients) or at a hospital with on-site cardiac surgery (917 patients). The rates of major adverse cardiac events were 9.5% in hospitals without on-site cardiac surgery and 9.4% in hospitals with on-site cardiac surgery at 30 days (relative risk, 1.00; 95% one-sided upper confidence limit, 1.22; P<0.001 for noninferiority) and 17.3% and 17.8%, respectively, at 12 months (relative risk, 0.98; 95% one-sided upper confidence limit, 1.13; P<0.001 for noninferiority). The rates of death, myocardial infarction, repeat revascularization, and stroke (the components of the primary end point) did not differ significantly between the groups at either time point. CONCLUSIONS: Nonemergency PCI procedures performed at hospitals in Massachusetts without on-site surgical services were noninferior to procedures performed at hospitals with on-site surgical services with respect to the 30-day and 1-year rates of clinical events. (Funded by the participating hospitals without on-site cardiac surgery; MASS COM ClinicalTrials.gov number, NCT01116882.).

Safety and feasibility of robotic percutaneous coronary intervention: PRECISE (Percutaneous Robotically-Enhanced Coronary Intervention) Study.

OBJECTIVES: The aim of this study was to evaluate the safety as well as the clinical and technical effectiveness of robotic-assisted percutaneous coronary intervention. BACKGROUND: Robotic systems have been suggested to enhance the performance of cardiovascular procedures, as well as to provide protection from the occupational hazards that are associated with interventional practice. METHODS: Patients with coronary artery disease and clinical indications for percutaneous intervention were enrolled. The coronary intervention was performed with the CorPath 200 robotic system, which consists of a remote interventional cockpit and a bedside disposable cassette that enables the operator to advance, retract, and rotate guidewires and catheters. The primary endpoints were clinical procedural success, defined as <30% residual stenosis at the completion of the robotic-assisted procedure without major adverse cardiovascular events within 30 days, and device technical success, defined as the successful manipulation of the intracoronary devices using the robotic system only. RESULTS: A total of 164 patients were enrolled at 9 sites. Percutaneous coronary intervention was completed successfully without conversion to manual operation, and device technical success was achieved in 162 of 164 patients (98.8%). There were no device-related complications. Clinical procedural success was achieved in 160 of 164 patients (97.6%), whereas 4 (2.4%) had periprocedural non-Q-wave myocardial infarctions. No deaths, strokes, Q-wave myocardial infarctions, or revascularization occurred in the 30 days after the procedures. Radiation exposure for the primary operator was 95.2% lower than the levels found at the traditional table position. CONCLUSIONS: This pivotal multicenter study with a robotic-enhanced coronary intervention system demonstrated the safety and feasibility of the system. The robotic remote-control procedure met the expected technical and clinical performance, with significantly lower radiation exposure to the operator. (Evaluation of the Safety and Effectiveness of the CorPath 200 System in Percutaneous Coronary Interventions [PCI] [PRECISE]; NCT01275092).

Left and codominant coronary artery circulations are associated with higher in-hospital mortality among patients undergoing percutaneous coronary intervention for acute coronary syndromes: report From the National Cardiovascular Database Cath Percutaneous Coronary Intervention (CathPCI) Registry.

BACKGROUND: Left or codominant coronary arterial circulation may represent less well-balanced myocardial perfusion and thus confer worse prognosis in acute coronary syndrome, especially for culprit lesions arising from the left coronary artery. METHODS AND RESULTS: We related left and codominance, relative to right dominance, with in-hospital mortality in 207 926 percutaneous coronary interventions (PCI) for acute coronary syndromes from July 1, 2009 through June 30, 2010 in the National Cardiovascular Data Registry Cath Percutaneous Coronary Intervention (CathPCI) Registry database version 4. Generalized estimating equations and logistic regression analyses were used in unadjusted and multivariable adjusted models. Models were adjusted using the validated National Cardiovascular Data Registry mortality risk model. We performed subgroup analyses and formally tested for effect modification by the epicardial coronary artery containing the culprit lesion. Left coronary dominance was associated with higher in-hospital mortality in unadjusted (odds ratio=1.29, 95% confidence interval [CI], 1.17-1.42) and adjusted models (1.19, 95% CI, 1.06-1.34). Codominance was associated with worsened mortality only in adjusted models (odds ratio=1.16, 95% CI, 1.01-1.34). Addition of coronary dominance to the National Cardiovascular Data Registry risk model did not materially change model discrimination or calibration. The odds of death for left versus right dominance among those with left circumflex or left main culprit lesions was 1.25 (95% CI, 1.02-1.53), for right coronary artery lesions was 1.19 (95% CI, 0.83-1.71), and for left anterior descending artery lesions was 1.09 (95% CI, 0.93-1.28). There was no statistical evidence for effect modification by culprit lesion vessel (P=0.8). CONCLUSIONS: Left and codominance are associated with modestly increased post-percutaneous coronary intervention in-hospital mortality in patients with acute coronary syndrome. Confirmation of these findings with angiographic core laboratory verification of coronary dominance and longer term follow-up will be desirable.

Cancer Therapy Targeting the HER2-PI3K Pathway: Potential Impact on the Heart.

The HER2-PI3K pathway is the one of the most mutated pathways in cancer. Several drugs targeting the major kinases of this pathway have been approved by the Food and Drug Administration and many are being tested in clinical trials for the treatment of various cancers. However, the HER2-PI3K pathway is also pivotal for maintaining the physiological function of the heart, especially in the presence of cardiac stress. Clinical studies have shown that in patients treated with doxorubicin concurrently with Trastuzumab, a monoclonal antibody that blocks the HER2 receptor, the New York Heart Association class III/IV heart failure was significantly increased compared to those who were treated with doxorubicin alone (16 vs. 3%). Studies in transgenic mice have also shown that other key kinases of this pathway, such as PI3Kα, PDK1, Akt, and mTOR, are important for protecting the heart from ischemia-reperfusion and aortic stenosis induced cardiac dysfunction. Studies, however, have also shown that inhibition of PI3Kγ improve cardiac function of a failing heart. In addition, results from transgenic mouse models are not always consistent with the outcome of the pharmacological inhibition of this pathway. Here, we will review these findings and discuss how we can address the cardiac side-effects caused by inhibition of this important pathway in both cancer and cardiac biology.

Robotic-assisted percutaneous coronary intervention--filling an unmet need.

Percutaneous coronary intervention (PCI) has undergone a remarkable evolution over the past 25 years. Initially, the procedure was limited to relatively straightforward lesions and was associated with significant risk and unpredictable long-term efficacy. With the incorporation of new technologies such as stents, the safety and efficacy of the procedure has improved dramatically. However, the fundamental way in which the procedure is performed has changed little since the time of Gruntzig's first successful case. Cumulative exposure to ionizing radiation, orthopedic injuries resulting from wearing shielding aprons, and fatigue from standing for hours at the table have made the catheterization laboratory a "high-risk workplace" for the interventional cardiologist. Robotic-assisted PCI was developed to allow the operator to precisely manipulate angioplasty guidewires, balloons, and stents from a radiation-shielded cockpit. A small first-in-man study demonstrated that PCI can be performed with robotic assistance. The pivotal Percutaneous Robotically Enhanced Coronary Intervention Study trial is currently enrolling patients and evaluating the safety and efficacy of the CorPath® robotically assisted PCI system.

Differential outcomes after sirolimus-eluting stent implantation: comparing on-label versus off-label patients in the 'real world'.

BACKGROUND: Randomized controlled trials indicate that sirolimus-eluting stents (SES) reduce the rates of restenosis and need for subsequent revascularization procedures, but patients enrolled in randomized trials represent a highly selected population. This study examined the performance of SES in a 'real world' setting by comparing the outcomes of trial-eligible versus ineligible patients undergoing percutaneous coronary intervention. METHODS: From the US commercial introduction of SES in April 2003 until December 2003, all patients that received an SES at our institution were followed in a prospective registry (n=838). For the purpose of this analysis, the registry population was divided into two groups based on the inclusion and exclusion criteria of the stenosis in a native coronary artery (SIRIUS) trial. The primary endpoint of the study was the rate of target lesion revascularization (TLR) at follow-up. Secondary endpoints included major adverse cardiac events (MACE) such as cardiac death, myocardial infarction, and target vessel revascularization. Clinical follow-up was complete for 92% of patients with a median duration of 14.2 months. RESULTS: Overall, 296 patients (35.3%) met entry criteria for the SIRIUS trial and thus comprised the SIRIUS eligible group. Patients in the SIRIUS ineligible group (n=542) were more likely to have chronic kidney disease and earlier bypass surgery and had longer mean stent length. At 1 year, TLR occurred in 3.0% of the SIRIUS eligible population and in 9.2% of the SIRIUS ineligible group (P=0.001). The secondary endpoint of cumulative MACE occurred in 6.6% of the SIRIUS eligible versus in 17.7% of the SIRIUS ineligible population (P<0.001). Two patients (0.4%) in the SIRIUS ineligible group had a late stent thrombosis on days 39 and 99, respectively, versus none in the SIRIUS eligible group. CONCLUSION: Among 'real world' patients treated with SES, the incidence of TLR and MACE at 1 year was substantially greater among SIRIUS ineligible patients compared with SIRIUS eligible patients. These findings confirm that pivotal clinical trials of drug-eluting stents tend to enroll low-risk patients and that the estimated rates of TLR and MACE derived from such trials may not reflect subsequent outcomes with unrestricted clinical use.

Correlates of adverse events during saphenous vein graft intervention with distal embolic protection: a PRIDE substudy.

OBJECTIVES: We sought to identify correlates of 30-day adverse events among patients undergoing percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG). BACKGROUND: Although the use of distal embolic protection devices during SVG intervention reduces major adverse cardiac events (MACE), many patients still experience MACE despite distal embolic protection, and the major predictors of MACE among these patients are not well-characterized. METHODS: Correlates of 30-day MACE and peri-procedural creatine kinase-myocardial band (CK-MB) elevation were assessed among 631 patients undergoing SVG intervention with distal embolic protection enrolled in the PRIDE (PRotection during saphenous vein graft Intervention to prevent Distal Embolization) study, a randomized comparison of the TriActiv System (Kensey-Nash Corp., Exton, Pennsylvania) with an active control group (Guardwire [Medtronic, Santa Clara, California] or Filterwire [Boston Scientific, Minneapolis, Minnesota]). RESULTS: Baseline covariates associated with MACE were longer lesion length, greater angiographically assessed estimated plaque volume, and higher SVG degeneration score. Graft age and angina class were not associated with adverse events. Angiographic lesion length was significantly correlated with more complex angiographic metrics such as estimated plaque volume and the SVG degeneration score. In multivariable analyses, angiographic lesion length was the strongest independent correlate of MACE (odds ratio [OR] 2.81 [95% confidence interval (CI) 1.82 to 4.34]/log-increase in lesion length, p < 0.001) with a graded increase in MACE observed with increasing lesion lengths. Similarly, the strongest independent correlate of CK-MB elevation was lesion length (OR 2.54 [95% CI 1.59 to 4.04]/log-increase in lesion length, p < 0.001). The associations between lesion length and both MACE and CK-MB elevation were consistent among the studied embolic protection devices (TriActiv, Guardwire, or Filterwire). CONCLUSIONS: Angiographic lesion length was the strongest correlate of short-term adverse events among patients undergoing SVG intervention with distal embolic protection, with incremental effects noted at even relatively short lesion lengths.