Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review.

In this systematic review, we sought to summarize the 3 recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials (Dapagliflozin Effect on CardiovasculAR Events (DECLARE-TIMI 58), Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, and Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME)) and to explore the potential causes for their different results. We found that the major adverse cardiovascular event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14% for DECLARE-TIMI 58, CANVAS, and EMPA-REG OUTCOME, respectively. DECLARETIMI 58 had the fewest cardiorenal events (across treatment and control arms) and EMPA-REG OUTCOME the most. DECLARE-TIMI 58 used alternative inclusion criterion for baseline renal function (creatinine clearance ≧ 60 mL/min) compared to the other trials (estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 bodysurface area). Therefore, the DECLARE-TIMI 58 study cohort had higher eGFR (mean eGFR 85.2 mL/min/1.73 m2 compared to 76.5 and 74 in CANVAS and EMPAREG OUTCOME, respectively); this may have caused the difference in results. Additionally contributing to the high event rate in EMPA-REG OUTCOME was the requirement of prior confirmed cardiovascular disease (CVD), resulting in 99.2% of patients with CVD compared to only 65.6% and 40.6% in CANVAS and DECLARE-TIMI 58, respectively (which did not require CVD). In conclusion, there is a need for large-scale studies of SGLT2i with matching inclusion/exclusion criteria and appropriate endpoints to ensure a truly direct comparison of the drugs.

Inhibition of the Sodium-Proton Antiporter (Exchanger) is a Plausible Mechanism of Potential Benefit and Harm for Drugs Designed to Block Sodium Glucose Co-transporter 2.

Clinical trials of sodium glucose co-transporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and comorbid cardiovascular and kidney disease have shown reductions in major adverse cardiovascular events, heart failure hospitalizations, and attenuation of the progression of kidney disease. The magnitude of benefit appears to be greater than expected due to glycemic control, reduced blood pressure, and loss of adiposity. This impact is also independent from reduced renal function and lesser degrees of natriuresis and glycosuria. However, these agents have also been associated with limb amputation, Fournier's gangrene, diabetic ketoacidosis, metabolic bone disease, and increased hematopoiesis. A strong off-target effect of SGLT2i on the sodium-proton antiporter (exchanger) on the cell surface and intracellular organelles explains the wide-ranging effects of these agents. By slowing the restoration of pH within cells, SGLT2i activate secondary processes that mimic ischemic preconditioning in the heart and kidney and increased hematopoiesis in bone marrow which would explain salutary effects. Conversely, the inability to rapidly recover pH in ischemic peripheral tissues explains the progression of diabetic extremity ulcers, gangrene, propensity for metabolic bone disease, and diabetic ketoacidosis in patients who are predisposed. This paper will review the evidence for the strong off-target effect of SGLT2i on the sodium-proton exchanger and its potential effect on the organ systems and processes in which SGLT2i appear to have activity.

Mitral Valve Perforation in Libman-Sacks Endocarditis: A Heart-Wrenching Case of Lupus.

Libman-Sacks (LS) endocarditis is one of the most common cardiac manifestations of systemic lupus erythematosus. Rarely, however, it can lead to serious complications, including severe valvular regurgitation or superimposed bacterial endocarditis. We describe the initial diagnostic challenges, clinical course, imaging studies and histopathological findings of a patient who presented with life-threatening lupus complicated by hemoptysis and respiratory failure secondary to a rare complication of LS endocarditis, acute mitral valve perforation. We review the current literature on valve perforation in the setting of LS endocarditis. In conclusion, although the disease is often asymptomatic and hemodynamically insignificant, it can result in serious and potentially fatal complications secondary to valve perforation, which may demand emergency surgical management.

Cardiac Computed Tomography Angiography in the Evaluation of Coronary Artery Disease: An Interventional Perspective.

Cardiac computed tomography angiography (CCTA) has become the gold standard for noninvasive anatomic assessment of the coronary arteries. With high positive predictive value and even higher negative predictive value, CCTA allows for rapid determination of the presence or absence of coronary plaque and triage of patients' need for further invasive evaluation and treatment. From an interventional cardiologist's perspective, CCTA (more so than stress testing) is helpful in determining the need for invasive therapy. In conjunction with functional assessments, the anatomic evaluation from CCTA mirrors the anatomical assessment of a coronary angiogram more than any other noninvasive assessment. This allows for catheter selection, percutaneous coronary intervention preplanning, as well as additional decision making before the patient has entered the catheterization laboratory. This manuscript explores some of the more recent developments in noninvasive coronary angiography and discusses the use and utility of CCTA from an interventional cardiologist's perspective.

Clinical Outcomes of Non-Stent-Based Interventions for Symptomatic Below-the-Knee Peripheral Artery Disease in the Excellence in Peripheral Artery Disease (XLPAD) Registry.

For endovascular treatment of below-the-knee (BTK) peripheral artery disease (PAD), independently adjudicated real-world outcomes comparing non-stent-based balloon angioplasty (percutaneous transluminal angioplasty) and adjunctive treatments with or without a concomitant ipsilateral femoropopliteal (FP) artery intervention are scarce. A total of 1,060 patients from the multicenter XLPAD registry who underwent non-stent-based BTK PAD intervention between 2006 and 2021 were included. The primary outcome was the 1-year incidence of major adverse limb events (MALEs), a composite of all-cause death, any amputation, or clinically driven repeat revascularization. A total of 566 patients underwent BTK and 494 BTK + FP interventions; 72% were men, with a mean age of 68.4 ± 10.9 years. Diabetes mellitus was more prevalent in the BTK-only group (76.5% vs 69%, p = 0.006). Mean Rutherford class was 4.2 ± 1.18; chronic limb-threatening ischemia was more frequent in the BTK group (55.3% vs 49%, p = 0.040). Moderate to severe calcification was more frequent in the BTK + FP group (21.2% vs 27.1%, p = 0.024), as was lesion length (110.6 ± 77.3 vs 135.4 ± 86.3 mm, p <0.001). Nearly 81% of lesions were treated with percutaneous transluminal angioplasty. Drug-coated balloon (1.6% vs 14%, p <0.001) and atherectomy (38% vs 58.5%, p <0.001) use was more frequent in the BTK + FP group. The rate of procedural success was higher in the BTK + FP group (86% vs 91%, p = 0.009), with amputation being the most common complication at 3.3% within 30 days after the procedure. The rates of 1-year MALE (21.2% vs 22.3%, p = 0.675) and mortality (4.6% vs 3.4%, p = 0.3) were similar between the BTK and BTK + FP groups. Nonstent treatment for BTK PAD with concomitant FP intervention leads to high procedural success and similar rates of 1-year MALE compared with isolated BTK intervention. Condensed Abstract: The vast majority of below-the-knee (BTK) peripheral artery disease (PAD) interventions are performed with balloon angioplasty. Presence of inflow femoropopliteal PAD in patients who undergo BTK interventions can affect the outcome of the procedure. This report explores immediate procedural success and major adverse limb events at 1 year after balloon angioplasty treatment for isolated BTK PAD and in patients who underwent an additional femoropopliteal PAD intervention.

Reproducibility of Femoropopliteal Artery Intravascular Ultrasound Imaging in Patients With Peripheral Artery Disease.

Despite increased use of intravascular ultrasound (IVUS) during peripheral artery interventions, evidence for reproducibility of IVUS measurements and its relation to angiography is lacking. Forty cross-sectional IVUS images of the femoropopliteal artery from 20 randomly selected patients enrolled in the XLPAD (Excellence in Peripheral Artery Disease) registry who underwent peripheral artery interventions and met criteria based on IVUS consensus guidelines were independently assessed by 2 blinded readers. IVUS images from 6 patients (40 images) were selected for angiographic correlation and met criteria for identifiable landmarks (e.g., stent edge and bifurcation). Lumen cross-sectional area (CSA), external elastic membrane (EEM) CSA, luminal diameter, and reference vessel diameter were repeatedly measured. The Lumen CSA and EEM CSA intra-observer agreement by Spearman rank-order correlation (ρ) was >0.993, intraclass correlation coefficient was >0.997, and repeatability coefficient was <1.34. For the interobserver measurement of luminal CSA and EEM CSA, the ρ = 0.742 and 0.764; intraclass correlation coefficient = 0.888 and 0.885; and repeatability coefficient = 7.24 and 11.34, respectively. A Bland-Altman plot for lumen and EEM CSA showed good reproducibility. For angiographic comparison, the ρ for luminal diameter, luminal area, and vessel area were 0.419, 0.414, and 0.649, respectively. Femoropopliteal IVUS measurements showed strong intra-observer and interobserver agreement; IVUS and angiographic measurements did not demonstrate a similar strong agreement.

Comparative Outcomes of Interventions for Femoropopliteal Chronic Total Occlusion Versus Non-Chronic Total Occlusion Lesions From the Multicenter XLPAD Registry.

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional balloon angioplasty (20.86% versus 33.48%, P<0.001) or drug-coated balloon angioplasty (1.26% versus 2.93%, P<0.001) were more frequent in the non-CTO group, whereas bare-metal stents (28.09% versus 20.22%, P<0.001) or covered stents (4.08% versus 1.83%, P<0.001) were more frequent in the CTO group. Debulking procedures were more commonly performed in the non-CTO group (41.44% versus 53.13%, P<0.001), despite a similar degree of calcification between the 2 groups. Procedural success was higher in the non-CTO group (90.12% versus 96.79%, P<0.001). Procedural complications were higher in the CTO group (7.21% versus 4.66%, P=0.002), mainly due to excess distal embolization (1.5% versus 0.6%, P=0.015). Adjusted 1-year major adverse limb events were higher in the CTO group (22.47% versus 18.77%, P=0.019), driven mainly by target limb revascularization (19.00% versus 15.34%, P=0.013). Conclusions Procedural success is lower for endovascular treatment of femoropopliteal CTO compared with non-CTO lesions. CTO lesions are associated with higher rates of periprocedural complications and reinterventions after 1 year.

Hybrid intervention approach to coronary artery and valvular heart disease.

Coronary angiography is used to assess the burden of coronary artery disease prior to surgical valve repair/replacement and often leads to concomitant bypass and valve surgery. We sought to evaluate outcomes of an alternative, hybrid approach involving percutaneous coronary intervention (PCI) and valve surgery, assessing the rate of stent thrombosis as a primary outcome. We reviewed charts of consecutive patients who underwent planned PCI prior to surgical valve repair/replacement by a single surgeon from January 2008 to December 2016. We calculated rates of surgical complication, duration of dual antiplatelet therapy (DAPT) prior to surgery, and rates of stent thrombosis and in-stent restenosis. Twenty-four patients were included in this study. Surgery was performed a median of 52.5 days following PCI. DAPT was withheld an average of 8 days before and resumed an average of 4 days after surgery. Ninety-two percent of surgeries were minimally invasive. There were no bleeding complications, stent thromboses, or restenosis events. All patients survived the 1-year follow-up. For patients with mixed coronary and valvular heart disease, a heart team approach involving preoperative PCI followed by staged minimally invasive valvular surgery appears to be safe and warrants further exploration.

Limitations of transoesophageal echocardiogram in acute ischaemic stroke.

Objective: The role of transoesophageal echocardiography (TOE) in identifying ischaemic stroke aetiology is debated. In 2018, the American Heart Association/American Stroke Association (AHA/ASA) issued class IIa recommendation for echocardiography, with the qualifying statement of use in cases where it will alter management. Hence, we sought to determine the rate at which TOE findings altered management in cases of confirmed ischaemic stroke. Methods: We retrospectively analysed TOE cases with confirmed ischaemic stroke at our centre between April 2015 and February 2017. We defined a change in management as the initiation of anticoagulation therapy, antibiotic therapy or patent foramen ovale closure as a direct result of TOE findings. Results: There were 185 patients included in this analysis; 19 (10%) experienced a change in management. However, only 7 of the 19 (4% of all subjects) experienced a change in management due to TOE findings. The remaining 12 were initiated on oral antigoagulation as a result of discoveries during routine workup, mainly atrial fibrillation on telemetry monitoring. Conclusions: This work suggests an overuse of TOE and provides support for the 2018 AHA/ASA stroke guidelines, which recommend against the routine use of echocardiography in the work up of cerebrovascular accident due to a cardioembolic source.

The effect of targeted temperature management on QT and corrected QT intervals in patients with cardiac arrest.

BACKGROUND: Targeted Temperature Management (TTM) improves outcomes after cardiac arrest but may affect the QT and QTc intervals which could increase the chance of subsequent arrhythmia. We report here the effects of TTM on both computer-derived and manually calculated QT and QTc as well as the relationship of the length of the QTc and serious arrhythmia in a retrospective single-center experience. METHODS: 193 patients undergoing TTM for cardiac arrest were studied. 12-lead electrocardiograms (ECG) were measured before, during and after TTM. We assessed the QT and Bazett-corrected QT intervals (QTc) and examined the relationship between QTc and the occurrence of malignant arrhythmias. RESULTS: Both the QT and QTc increased during TTM whether derived manually or from the computer algorithm, although values were different with the two methods. Neither the QT nor the QTc were significantly longer in those patients with malignant arrhythmias. CONCLUSIONS: QT and QTc prolong during TTM. There was no differential increase in the QTc in patients who experienced malignant arrhythmias. While the mechanism of QTc prolongation is not clear, it would not appear that the degree of QTc prolongation has an adverse effect on cardiac rhythm during TTM.