Robert D. Safian

Pulmonary vein stenosis: recognizing an important cause of dyspnea after pulmonary vein isolation.

Pulmonary vein (PV) stenosis is a serious and potentially disabling complication after PV ablation. The incidence of PV stenosis depends on the definition of stenosis and on the rigor with which imaging studies are performed after PV isolation [1]. Although the incidence of severe PV stenosis (diameter stenosis 70%) has been reported as 0–8%, most series report rates 1.5% within 1 year of ablation [2]; rates are higher for diameter stenosis of 20–50%. As is true with other types of vascular injury, PV stenosis appears to be a response to thermal injury leading to intimal and smooth muscle cell proliferation, pathophysiologically similar to restenosis after conventional balloon angioplasty, laser balloon angioplasty, atherectomy, and stenting. Our electrophysiology colleagues have already learned that the risk of PV stenosis may be reduced by modifying the ablation technique and by targeting certain regions for ablation; the extent of injury and the risk of PV stenosis are higher when radiofrequency energy is delivered at high temperature (>55 C) and power (>35 Watts), particularly, if ablation is performed within the PV ostium. Various imaging techniques have been used in an effort to localize (and avoid) the PV ostia, including fluoroscopy, computerized tomography (CT), magnetic resonance imaging, venography, real-time impedance measurements, and intracardiac echocardiography, but even despite rigorous efforts, injury to the PV ostia may still occur. The most common diagnostic dilemma is that dyspnea due to PV stenosis is indistinguishable from other more common causes of dyspnea. Most patients with severe stenosis of two or more PVs experience significant dyspnea with exertion, and many of these patients undergo extensive evaluations by internists and pulmonary specialists without specific diagnosis; even general cardiologists may fail to consider PV stenosis if echocardiography fails to identify a cardiac etiology. Accordingly, there should be a high index of suspicion for PV stenosis in patients who develop dyspnea after PV isolation, especially if an obvious pulmonary cause cannot be identified. Some institutions recommend routine serial CT angiography at 1, 3, 6, and 12 months after ablation (regardless of symptom status), whereas other centers perform serial CT angiograms only if the study at 3 months identifies a degree of PV stenosis. Even though the natural history of mild PV stenosis has not been clearly defined, one study identified progression and regression of stenosis in 10 and 30% of patients, respectively [3]. An interesting observation is that quantitative ventilation/perfusion (V/Q) scans become abnormal when both left upper and lower PV stenoses exceed 70%, whereas perfusion abnormalities may be observed with right upper and lower PV stenoses of 55–69%. V/Q scans can also be useful for objective assessment of the degree of baseline perfusion abnormality, and for serial assessment after revascularization. A clinically important subset is the patient who develops PV occlusion after ablation. In this issue of Catheterization and Cardiovascular Intervention, Hill and colleagues report their outcomes of percutaneous intervention in 16 patients with PV occlusion (among 116 patients with PV stenosis) during a 7-year interval from 2005–2012 [4]. Outcomes included procedural success in 78% (79% were treated initially with angioplasty without stenting), reocclusion in 54% within 3.6 months, successful reintervention in 83%, and continued primary and secondary patency in 69% at median follow up of 13 months. Since this study was reported by pediatric cardiologists and included a mix of infants, teenagers, and adults, it may not be

Validity of estimated glomerular filtration rates for assessment of renal function after renal artery stenting in patients with atherosclerotic renal artery stenosis.

OBJECTIVES The purpose of this study was to evaluate the validity of estimates of glomerular filtration rate (eGFR) for assessing serial changes in renal function after renal artery stenting. BACKGROUND eGFR are unreliable for assessing serial renal function in patients with atherosclerotic renal artery stenosis (RAS). eGFR have not been validated for assessment of serial renal function after renal artery stenting. METHODS Serum creatinine (SCr) and (125)I-iothalamate GFR (iGFR) were measured in RAS patients before and after renal artery stenting. eGFR were calculated from Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault (CG) formulas. Using iGFR as the reference standard, the sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) were determined for MDRD, CKD-EPI, and CG for assessing changes in GFR before and after intervention. RESULTS Between 1998 and 2007, 84 patients underwent iGFR and eGFR before and after renal artery stenting. All eGFR demonstrated poor sensitivity and reliability for detecting ≥20% changes in iGFR, and poor agreement in the magnitude and direction of change in iGFR, before and after renal stenting. CONCLUSIONS In RAS patients, eGFR demonstrate poor sensitivity and reliability for detecting meaningful changes in iGFR after renal artery stenting. eGFR should be abandoned as primary endpoints in major clinical trials assessing the impact of renal revascularization on renal function.

Invasive characterization of atherosclerotic plaque in patients with peripheral arterial disease using near‐infrared spectroscopy intravascular ultrasound

We describe the characteristics of atherosclerotic plaque in patients with peripheral arterial disease (PAD) using near‐infrared spectroscopy‐intravascular ultrasound (NIRS‐IVUS)

Coronary artery aneurysms: case report and review of transcatheter management strategies.

There is no consensus on the best management of coronary artery aneurysms (CAA) in adults. We describe two patients with CAA and review transcatheter approaches to exclude them from the circulation.

Percutaneous mitral valve repair for mitral regurgitation: zipping-by-clipping.

In March 2013, the Circulatory System Devices advisory panel of the Food and Drug Administration recommended approval of the MitraClip (Abbott Vascular, Santa Clara, CA) for patients with severe mitral regurgitation (MR) who are at high risk for surgical repair or replacement. There was uniform agreement among the panel members about the safety of the MitraClip, but considerable debate about its efficacy. Much of the controversy about device efficacy stems from the lack of convincing data from randomized clinical trials to support using the MitraClip, relative to established therapies for MR. So, how did we get to this point, and where do we go from here? In my opinion, the two most important issues about the MitraClip are which patients should be treated, and how much MR reduction should be pursued? With regard to the first issue, it seems pretty clear that surgical repair/replacement is superior to MitraClip for MR reduction in patients with degenerative MR who are acceptable candidates for surgery, as suggested by the randomized EVEREST-II trial [1]; the MitraClip may be better suited for patients with significant left ventricular dysfunction and functional MR who are poor candidates for surgery [2,3]. One can argue that EVEREST-II was overly ambitious, and that the ongoing COAPT trial (Clinical Outcomes Assessment of the MitraClip Therapy Percutaneous Therapy for High Surgical Risk Patients) will provide a better assessment of the efficacy of the MitraClip in high-risk patients, by randomizing 400 patients to MitraClip or best medical therapy. However, the second issue about MR reduction is quite murky. For those of us who perform these procedures, the technical aspects are often less laborious than the cognitive aspects of device placement, assessment of residual MR before final clip deployment, and judgments about using multiple clips (MC). In my own experience, I have often likened this to the game of “Whac-A-Mole,” wherein you hit a mole at one location, only to have another pop-up in a different location. Most often we try to position the MitraClip in the center of the vena contracta, only to find another jet of MR “pop-up” more medial or lateral to the intended clip position. This observation may lead to several sequences of release, repositioning, and regrasping leaflets, with the goal of obtaining that ideal single clip (SC) position, or biasing the clip more medially or laterally with the intent of using another clip to treat residual MR. The decision to use more than one clip is heavily influenced by the degree of residual MR (and sometimes we feel that mild MR is “good enough”), the transmitral pressure gradient (TMG), and the mitral valve orifice area (MVOA), not to mention the degree of difficulty and angst associated with placement of the first clip. Fortunately, this issue of Catheterization and Cardiovascular Intervention provides interesting observations and insights into MR reduction by the MitraClip. Paranskaya et al. report their single-center results in 85 consecutive high risk patients who underwent SC and MC interventions, with the intention of eliminating MR [4]. Patients with vena contracta diameter >10 mm and those with complex or multiple MR jets were considered a priori for MC; their institutional “cut-off” for no additional clip implants was TMG 4 mm Hg and MVOA 2.5 cm. The MC strategy was to start at the A3-P3 (posteromedial) commissure and move towards the A1-P1 (anterolateral) commissure, using the so-called “zipping-by-clipping” technique [5]. These are very experienced operators who perform about one MitraClip procedure per week, and the patients were nearly equally divided among degenerative (43.5%) and functional (56.5%) MR. Patients

Complications and Solutions with Carotid Stenting

Complications of carotid stenting can be classified as neurologic, cardiovascular, death, carotid, access site, device malfunctions, and general and late complications. The risk of most complications is related to readily identifiable patient and anatomic factors. Management and outcome of complications require immediate recognition and a team-based approach to patient care.

Vascular complications during TAVR: The cost of doing business.

Transcatheter aortic valve replacement (TAVR) has proven superiority to standard medical therapy in inoperable patients with symptomatic severe aortic stenosis, and is equivalent to surgical AVR in high-risk patients [1,2]. Although two devices are currently available in the United States for commercial or investigational use, there are more than 15 devices in various stages of investigation or approval outside the United States. Transfemoral (TF) TAVR is the most commonly employed technique, although other arterial (subclavian, axillary, aortic, transapical) and venous (transseptal, cavoaortic) approaches have been utilized in patients who are unsuitable for the TF approach. Large vascular sheaths (18–24 Fr) are required for TF TAVR, and all patients require careful preoperative multimodality imaging to ensure suitability, based on aortiliac and common femoral arterial dimensions, distribution and extent of calcification, tortuosity, and the diameter of the valve implant. Computerized tomography angiography is widely utilized for vascular decision-making, and patients deemed suitable for TF TAVR usually undergo surgical cutdown for arterial access and surgical repair for hemostasis. Unfortunately, vascular complications have been reported in 8–30% of TF TAVR. Despite improvements in operator experience, patient selection, and valve delivery systems, vascular complications still contribute to significant patient morbidity and are strong predictors of TAVR-related mortality. Accordingly, there is considerable interest in converting TAVR to a fully percutaneous procedure, with the hope of reducing the incidence of vascular complications. In this issue of Catheterization and Cardiovascular Intervention, Holper et al. report the results of a randomized trial of surgical cutdown versus percutaneous access in 30 TAVR patients during a 6-month period in 2011 [3]. Hemostasis was achieved using protamine in all patients, surgical repair in the cutdown group, and the preclosure technique with >2 Perclose ProGlide devices (Abbott Vascular, Santa Clara, CA) in the percutaneous group. The primary endpoint of the study, the composite incidence of major and minor vascular complications (as defined by the Valve Academic Research Consortium-2) was 26.7%, and was identical in both groups (using intention-to-treat and as-treated analyses). These complications included dissection, perforation, and new stenosis, and most (75%) were treated with angioplasty or stents. Time to ambulation and narcotic usage were similar in both groups. However, although this study is timely, it may not have broad applicability for several reasons. First, the study is very small and only 14 patients in each group received their intended femoral access. Second, the authors did not distinguish true access site complications related to the common femoral artery from those related to proximal injury to the common or external iliac artery; complications in the latter distribution may be due to the guidewire or the sheath, rather than access site injury per se. Finally, it is not clear whether the authors used the ideal approaches to femoral access and hemostasis in their percutaneous group. Reliable percutaneous femoral access (above the femoral bifiurcation and below the inferior epigastric artery) is achieved with ultrasound-guided micropuncture access or roadmapping the common femoral artery by selective femoral crossover angiography prior to sheath placement [4]. From a hemostasis standpoint, while preclosure with >2 ProGlide devices may be suitable for sheaths<18 French, experience with 18–24 Fr sheaths for TAVR and endovascular aneurysm repair suggests that

Arterial access for limb salvage for critical limb ischemia: How low (and how small) can we go?

The presence of critical limb ischemia (CLI) identifies a patient with a high risk for cardiovascular mortality and limb loss, and mandates strong interdisciplinary collaboration between endovascular interventionalists, vascular surgeons, wound care specialists, cardiologists, and medical specialists with expertise in management of diabetes, chronic kidney disease, and infectious diseases. From a cognitive standpoint, two inter-related clinical principles have emerged that have significant clinical relevance for CLI patients [1]. The first is the angiosome concept, which identifies six anatomic units in the foot, each consisting of discrete regions of arterial blood flow. The anterior tibial/dorsalis pedis artery supplies one angiosome (primarily the dorsum of the foot); the posterior tibial artery supplies three angiosomes via the calcaneal branch (medial plantar surface of the heel), the medial plantar artery (the medial plantar surface of the foot), and the lateral plantar artery (the great toe and most of the plantar surface of the foot except for the lateral heel); and the peroneal artery supplies two angiosomes via the anterior perforating branch (area overlying the lateral malleolus) and the calcaneal branch (lateral and plantar surface of the heel). The second is the concept of direct versus indirect revascularization; direct revascularization requires straight in-line revascularization of the artery that supplies the affected angiosome, whereas indirect revascularization relies on improvement in collateral blood flow to the affected angiosome via the pedal arch, usually because direct revascularization is not technically feasible. In terms of limb salvage, the major goals are to avoid or to limit the extent of amputation, promote wound healing, and provide the patient with a functional limb, to the extent allowable by surgical bypass and/or percutaneous revascularization. From a technical perspective, there have been truly remarkable achievements in percutaneous revascularization of the superficial femoral artery, including antegrade femoral and retrograde popliteal approaches, relying on angiographic and ultrasound roadmaps to enhance procedural safety, and intraluminal and subintimal crossing techniques to enhance procedural success. There is growing interest in direct pedal access for retrograde recanalization, when antegrade recanalization is not feasible [2]. Incredibly, in this issue of Catheterization and Cardiovascular Intervention, Palena et al. demonstrate further ingenuity by performing direct access to the first dorsal metatarsal artery in 38 patients with infrapopliteal disease and CLI refractory to “standard” antegrade femoral or retrograde pedal approaches [3]. In this remarkable study, the authors achieved direct revascularization of the affected angiosome in 33 of 38 patients (87%), resulting in marked improvement in transcutaneous oxygen tension, avoidance of major amputation, amputation-free survival in 81.5% at 12 months, and absence of serious complications. However, significant challenges with this technique include the requirement for angiographic roadmapping to achieve arterial access (which may be problematic when tibial blood flow is poor), high radiation exposure due to prolonged fluoroscopy times, and technical failure in 13.5% due to refractory vasospasm or obliterative atherosclerosis precluding guidewire crossing of tibial artery occlusions. Furthermore, although the strategy of direct revascularization is associated with faster wound healing, direct and indirect revascularization seem to be associated with similar rates of subsequent amputation, raising a question as to the need for transmetatarsal recanalization [4]. Nevertheless, the technical achievements are impressive, and the study demonstrates just “how low (and how small) we can go.” Further improvement in ultrasound guidance and in

Expert consensus statement on FFR, IVUS, and OCT: focus on physiology and luminology.

Invasive coronary angiography has been the gold standard for assessment of coronary stenosis severity for more than 50 years, and was the cornerstone of recommendations for surgical and percutaneous revascularization. In 1988, Topol used the phrase “oculostenotic reflex” to characterize the frequent practice of interventional cardiologists to perform angioplasty on angiographically significant stenoses without considering objective measures of myocardial ischemia [1]. As stenting supplanted angioplasty as the dominant technique for percutaneous coronary intervention (PCI), the temptation to deploy stents to achieve perfect immediate angiographic results was nearly irresistible. Early invasive techniques for intravascular imaging [such as intravascular ultrasound (IVUS) and angioscopy] and hemodynamic assessment (such as coronary flow reserve) were utilized by some centers to acquire additional objective information, but these techniques were not incorporated into routine interventional practice until later studies demonstrated their clinical relevance. In this issue of Catheterization and Cardiovascular Intervention, Lofti and colleagues published an expert consensus statement of the Society of Cardiovascular Angiography and Interventions (SCAI) on the use of IVUS, fractional flow reserve (FFR), and optical coherence tomography (OCT), which constitute important contemporary techniques for intravascular imaging and hemodynamic assessment of coronary artery disease [2]. This document details the base of evidence supporting the use of FFR for determining the functional significance of coronary stenoses and improving PCI outcomes in important angiographic subsets (intermediate stenosis severity, ambiguous lesions, left main disease, serial stenoses, and multivessel disease); the use of IVUS for obtaining high-resolution images to measure lumen, plaque, and vessel dimensions (particularly in left main and bifurcation lesions); and the use of OCT for advanced characterization of the arterial lumen (especially for intraluminal thrombus, stent edge dissection, and stent underexpansion). The SCAI recommends FFR for physiological lesion assessment to help guide the need for revascularization (analogous to the use of preprocedural stress testing), and IVUS or OCT for determining optimal stent deployment after PCI. The SCAI is a dedicated and authoritative professional organization for interventional cardiologists, and the present consensus statement is representative of SCAI leadership in our specialty. This document from an expert writing group is completely consistent with our understanding of the limitations of contrast angiography with regard to physiology, luminology, and appropriateness criteria for PCI, focusing attention on objective delineation of lesion significance based on physiological assessment or on “true” lesion dimensions [3]. There is less attention to comprehensive plaque characterization and delineation of coregistered plaque composition and architecture by direct coronary imaging techniques using IVUS-virtual histology and near-infrared spectroscopy-IVUS. There is a growing body of evidence that combined architectural and compositional plaque characteristics may have important implications for identifying vulnerable plaque (with attendant risks of plaque rupture, acute myocardial infarction, and sudden cardiac death) and identifying lesions at risk for distal embolization after PCI [4,5]. Although current data may not be sufficient to support guideline recommendations, hopefully future consensus documents will be able to comment on the clinical applications of these novel technologies.

Carotid artery stenting: Looking at the bright side of regulatory oversight

In contemporary cardiovascular medicine, few procedures have received such intense scrutiny, have been the subject of such widespread study, and have engendered so much interdisciplinary controversy as carotid artery stenting (CAS). Although carotid endarterectomy (CEA) receives widespread reimbursement even when applied outside the clinical boundaries of the “landmark” CEA trials of the 1990’s, the national coverage determination (NCD) from the Center for Medicare and Medicaid Services (CMS) restricts reimbursement for CAS to symptomatic patients at high risk for CEA and to asymptomatic high-risk patients enrolled in trials or registries approved by the Food and Drug Administration (FDA). Most CAS operators and several professional societies believe that the CMS NCD policy is outdated, is inconsistent with the results of large randomized clinical trials and registries that demonstrate equipoise between CAS and CEA, and is mired in the turf struggles between interventional cardiologists, vascular surgeons, and neurologists. Despite an enormous evidence base supporting CAS, many cardiovascular societies, including the Society for Cardiac Angiography and Intervention and the American College of Cardiology have failed to lobby successfully for changes to the NCD. While there is no question that most interventional cardiologists would regard the NCD as a clear barrier to CAS, it is compelling that one of the world’s foremost CAS experts believes that there is a strong link between FDA regulatory approval, CMS NCD, and the outcome of CAS. In this issue of Catheterization and Cardiovascular Intervention, Gray and Verta review the outcomes of CAS in all FDA-sponsored clinical trials from 2000 to 2012, including investigational device exemption (IDE) trials and postmarket approval (PMA) registries [1]; several salient points are remarkable. First, the base of evidence is comprised of nearly 50,000 patients treated with CAS. Second, the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy study set the standards for dispassionate evaluation of CAS and CEA that have been incorporated into all subsequent CAS, IDE, and PMA studies [2], relying on common inclusion and exclusion criteria, shared definitions of primary and secondary endpoints, independent assessment and adjudication of neurological and cardiovascular events, and requirement for use of dual antiplatelet therapy and embolic protection devices (EPDs). Third, the time period of study included several regulatory milestones, including FDA approval of seven stent systems and 510(k) approval of 12 EPDs; all of these studies met their primary endpoint. Fourth, CAS experience was divided into an early (2000–2004) and late (2005–2012) experience; compared to early high-risk patients, late CAS high-risk patients experienced a marked decline in the 30-day risk of death and stroke (overall, 2.6% vs. 5.3%), including symptomatic (5.1% vs. 11.6%), and asymptomatic (2.8% vs. 5.4%) patients. Similarly, there was marked decline in death and stroke in standard risk symptomatic patients (1.8% vs. 4.4%). Appropriately, Gray and Verta attribute the favorable temporal changes in outcome to an interaction between several factors, including technological improvements in stent and EPD design, and enhancements in physician knowledge, experience, and judgment. The authors suggest that these improvements are “linked” to FDA regulatory approval and CMS coverage decisions. The premise that FDA and Medicare regulations have led to improved outcomes may represent the bright side of regulatory oversight, although I am skeptical that FDA and CMS intended to improve outcomes rather than limit CAS availability. Nevertheless, there is no