Impact of diabetes in patients waiting for invasive cardiac procedures during COVID-19 pandemic.

BACKGROUND: During COVID-19 pandemic, elective invasive cardiac procedures (ICP) have been frequently cancelled or postponed. Consequences may be more evident in patients with diabetes. OBJECTIVES: The objective was to identify the peculiarities of patients with DM among those in whom ICP were cancelled or postponed due to the COVID-19 pandemic, as well as to identify subgroups in which the influence of DM has higher impact on the clinical outcome. METHODS: We included 2,158 patients in whom an elective ICP was cancelled or postponed during COVID-19 pandemic in 37 hospitals in Spain. Among them, 700 (32.4%) were diabetics. Patients with and without diabetes were compared. RESULTS: Patients with diabetes were older and had a higher prevalence of other cardiovascular risk factors, previous cardiovascular history and co-morbidities. Diabetics had a higher mortality (3.0% vs. 1.0%; p = 0.001) and cardiovascular mortality (1.9% vs. 0.4%; p = 0.001). Differences were especially important in patients with valvular heart disease (mortality 6.9% vs 1.7% [p < 0.001] and cardiovascular mortality 4.9% vs 0.9% [p = 0.002] in patients with and without diabetes, respectively). In the multivariable analysis, diabetes remained as an independent risk factor both for overall and cardiovascular mortality. No significant interaction was found with other clinical variables. CONCLUSION: Among patients in whom an elective invasive cardiac procedure is cancelled or postponed during COVID-19 pandemic, mortality and cardiovascular mortality is higher in patients with diabetes, irrespectively on other clinical conditions. These procedures should not be cancelled in patients with diabetes.

Consequences of canceling elective invasive cardiac procedures during Covid-19 outbreak.

BACKGROUND: During COVID-19 pandemic in Spain, elective procedures were canceled or postponed, mainly due to health care systems overwhelming. OBJECTIVE: The objective of this study was to evaluate the consequences of interrupting invasive procedures in patients with chronic cardiac diseases due to the COVID-19 outbreak in Spain. METHODS: The study population is comprised of 2,158 patients that were pending on elective cardiac invasive procedures in 37 hospitals in Spain on the 14th of March 2020, when a state of alarm and subsequent lockdown was declared in Spain due to the COVID-19 pandemic. These patients were followed-up until April 31th. RESULTS: Out of the 2,158 patients, 36 (1.7%) died. Mortality was significantly higher in patients pending on structural procedures (4.5% vs. 0.8%, respectively; p < .001), in those >80 year-old (5.1% vs. 0.7%, p < .001), and in presence of diabetes (2.7% vs. 0.9%, p = .001), hypertension (2.0% vs. 0.6%, p = .014), hypercholesterolemia (2.0% vs. 0.9%, p = .026) [Correction added on December 23, 2020, after first online publication: as per Dr. Moreno's request changes in p-values were made after original publication in Abstract.], chronic renal failure (6.0% vs. 1.2%, p < .001), NYHA > II (3.8% vs. 1.2%, p = .001), and CCS > II (4.2% vs. 1.4%, p = .013), whereas was it was significantly lower in smokers (0.5% vs. 1.9%, p = .013). Multivariable analysis identified age > 80, diabetes, renal failure and CCS > II as independent predictors for mortality. CONCLUSION: Mortality at 45 days during COVID-19 outbreak in patients with chronic cardiovascular diseases included in a waiting list due to cancellation of invasive elective procedures was 1.7%. Some clinical characteristics may be of help in patient selection for being promptly treated when similar situations happen in the future.

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI.

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). CONCLUSIONS: Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .).

A coronary "tunnel": optical coherence tomography assessment after rotational atherectomy.

A 81-year-old woman was admitted for exertional angina. Coronary angiogram revealed a severely calcific proximal circumflex lesion. Rotational atherectomy was performed with 1.5 and 1.75 burrs, obtaining a good angiographic result. Optical coherence tomography (OCT) assessment revealed a large dissection parallel to the true lumen. We implanted a 3.0 mm × 38 mm Xience Prime(®) stent and postdilated it with a 3.0-mm non-compliant balloon. Final OCT pullback showed mild malapposed struts with large lumen area. 3D-OCT reconstruction confirmed a large lumen after stent implantation.

Difficulties with horizontal aortic root in transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) emerged to be a viable treatment option for failing bioprosthesis in the aortic position. Transfemoral approach is the most common access route for TAVI and associated with most favorable clinical outcome. However, in the presence of unfavorable aortic root anatomy, TAVI via transfemoral approach provides inadequate support for device manipulation during valve positioning, particularly performed for the indication of severe aortic regurgitation. We report our experience on TAVI utilizing CoreValve for a patient with regurgitant failing bioprosthesis with horizontal aortic root where we encountered difficulties during implantation and retrieval of valve delivery system.

Crush, culotte, T and protrusion: which 2-stent technique for treatment of true bifurcation lesions? - insights from in vitro experiments and micro-computed tomography.

BACKGROUND: Percutaneous coronary intervention of complex true bifurcation lesions often fails to ensure continuous stent coverage and strut apposition in both the side branch and main vessel. Struts left unopposed floating in the lumen disturb blood flow and are increasingly recognized as increasing the risk of stent thrombosis. METHODS AND RESULTS: In this study, we compared the results of different bifurcation treatment strategies: Crush (n=5); Culotte (n=3); T-/T with Protrusion (TAP) (n=4) using drug-eluting stents deployed in-vitro in representative coronary bifurcation models. After final kissing balloon post-dilatation, the rate of malapposition within the bifurcation quantified from micro-computed tomography scanning was on average 41.5 ± 8.2% with the Crush technique, reduced to respectively 31.4 ± 5.2% with Culotte and 36.7 ± 8.0% with T-/TAP approach. Overlaying layers of struts in the Crush and Culotte techniques lead to a significantly higher rate of strut malapposition in the proximal vessel than with the T-/TAP technique (Crush: 39.1 ± 10.7%, Culotte: 26.1 ± 7.7%, TAP: 4.2 ± 7.2%, P<0.01). Maximal wall-malapposed strut distance was also found on average to be higher with the Crush (1.36 ± 0.4mm) and Culotte techniques (1.32 ± 0.1mm) than with T-/TAP (1.08 ± 0.1mm, P=0.04). CONCLUSIONS: In this model, the Crush technique resulted in a higher risk of malapposition than either the Culotte or T-/TAP technique.

Real-world experience of MitraClip for treatment of severe mitral regurgitation.

BACKGROUND: Percutaneous edge-to-edge mitral valve repair with the MitraClip(®) was shown to be a safe and feasible alternative compared to conventional surgical mitral valve repair. Herein is reported our experience on MitraClip(®) for high-risk surgical candidates with severe mitral regurgitation (MR). METHODS AND RESULTS: Patients with severe MR (3 or 4+) and high operative risk were considered for MitraClip(®) implantation. Device success was defined as placement of 1 or more MitraClips(®) with reduction of MR to ≤2+. Patients were followed up clinically and with echocardiography at 1 year. A total of 27 patients with severe MR (age, 74±12 years; 17 male; logistic EuroSCORE, 27±12; left ventricular ejection fraction, 40±17%) were treated. Fifty-six percent of MR was degenerative and 44% was functional. Device success was 93% with 14 patients receiving 2 clips. MR severity was reduced from 3.5±0.5 to 1.7±0.8 (P<0.001); New York Heart Association class improved from 3.1±0.4 to 2.0±0.8 (P<0.001). In 45% of functional and in 29% of degenerative MR patients, to avoid mitral stenosis, additional MitraClip(®) implantation was not attempted, with resultant transmitral mean gradient of 4.9±1.6mmHg vs. 3.1±1.4mmHg, respectively (P=0.01). CONCLUSIONS: MitraClip(®) was shown to be an effective and safe treatment for patients with both functional and degenerative MR. Inability to obtain a greater reduction of MR was the consequence of borderline transmitral gradient requiring a compromise to avoid mitral stenosis, particularly in the functional MR patients.

Edge-to-edge percutaneous repair of severe mitral regurgitation--state-of-the-art for Mitraclip® implantation.

MitraClip® therapy is a percutaneous edge-to-edge plication of the mitral leaflets, mimicking the Alfieri surgical technique. MitraClip® implantation is a safe procedure, and survival outcomes in high-surgical-risk patients are superior to historical controls. Despite these results, questions remain concerning long-term efficacy and durability. The MitraClip® device has been studied in a safety and feasibility trial in the USA, a randomized pivotal trial against surgical mitral valve repair. Moreover, MitraClip® now has over 2 years of CE-mark approval and a rapidly expanding clinical experience in Europe, primarily in patients at high risk for surgery. A dedicated multidisciplinary team is necessary, as well as thoughtful patient selection, familiarity with the technical aspects of the procedure, including transesophageal ultrasound imaging and post-procedure monitoring. Currently available clinical data and procedural steps are herein reviewed. Because the MitraClip® procedure is still relatively new, continued investigation is required to further better define the patient populations that will benefit most.

Sex Differences in Instantaneous Wave-Free Ratio or Fractional Flow Reserve-Guided Revascularization Strategy.

OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 ± 0.51 vs. 0.43 ± 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 ± 0.09 vs. 0.91 ± 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 ± 0.09 vs. 0.85 ± 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

Clinical Events After Deferral of LAD Revascularization Following Physiological Coronary Assessment.

BACKGROUND: Physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR). OBJECTIVES: The purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial. METHODS: MACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex. RESULTS: A total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06). CONCLUSIONS: iFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral.

Comparison of Major Adverse Cardiac Events Between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients With or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Invasive physiologic indices such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are used in clinical practice. Nevertheless, comparative prognostic outcomes of iFR-guided and FFR-guided treatment in patients with type 2 diabetes have not yet been fully investigated. Objective: To compare 1-year clinical outcomes of iFR-guided or FFR-guided treatment in patients with and without diabetes in the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization (DEFINE-FLAIR) trial. Design, Setting, and Participants: The DEFINE-FLAIR trial is a multicenter, international, randomized, double-blinded trial that randomly assigned 2492 patients in a 1:1 ratio to undergo either iFR-guided or FFR-guided coronary revascularization. Patients were eligible for trial inclusion if they had intermediate coronary artery disease (40%-70% diameter stenosis) in at least 1 native coronary artery. Data were analyzed between January 2014 and December 2015. Interventions: According to the study protocol, iFR of 0.89 or less and FFR of 0.80 or less were used as criteria for revascularization. When iFR or FFR was higher than the prespecified threshold, revascularization was deferred. Main Outcomes and Measures: The primary end point was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. The incidence of MACE was compared according to the presence of diabetes in iFR-guided and FFR-guided groups. Results: Among the total trial population (2492 patients), 758 patients (30.4%) had diabetes. Mean age of the patients was 66 years, 76% were men (1868 of 2465), and 80% of patients presented with stable angina (1983 of 2465). In the nondiabetes population (68.5%; 1707 patients), iFR guidance was associated with a significantly higher rate of deferral of revascularization than the FFR-guided group (56.5% [n = 477 of 844] vs 46.6% [n = 402 of 863]; P < .001). However, it was not different between the 2 groups in the diabetes population (42.1% [n = 161 of 382] vs 47.1% [n = 177 of 376]; P = .15). At 1 year, the diabetes population showed a significantly higher rate of MACE than the nondiabetes population (8.6% vs 5.6%; adjusted hazard ratio [HR], 1.88; 95% CI, 1.28-2.64; P < .001). However, there was no significant difference in MACE rates between iFR-guided and FFR-guided groups in both the diabetes (10.0% vs 7.2%; adjusted HR, 1.33; 95% CI, 0.78-2.25; P = .30) and nondiabetes population (4.7% vs 6.4%; HR, 0.83; 95% CI, 0.51-1.35; P = .45) (interaction P = .25). Conclusions and Relevance: The diabetes population showed significantly higher risk of MACE than the nondiabetes population, even with the iFR-guided or FFR-guided treatment. The iFR-guided and FFR-guided treatment showed comparable risk of MACE and provided equal safety in selecting revascularization target among patients with diabetes. Trial Registration: ClinicalTrials.gov identifier: NCT02053038.

Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes.

OBJECTIVES: The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND: Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS: The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS: Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS: Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.

Cardiovascular Safety in Drug Development: A Role for Endothelial Function Tests.

As drug development becomes a long and demanding process, it might also become a barrier to medical progress. Drug safety concerns are responsible for many of the resources consumed in launching a new drug. Despite the money and time expended on it, a significant number of drugs are withdrawn years or decades after being in the market. Cardiovascular toxicity is one of the major reasons for those late withdrawals, meaning that many patients are exposed to unexpected serious cardiovascular risks. It seems that current methods to assess cardiovascular safety are imperfect, so new approaches to avoid the exposure to those undesirable effects are quite necessary. Endothelial dysfunction is the earliest detectable pathophysiological abnormality, which leads to the development of atherosclerosis, and it is also an independent predictor for major cardiovascular events. Endothelial toxicity might be the culprit of the cardiovascular adverse effects observed with a significant number of drugs. In this article, we suggest the regular inclusion of the best validated and less invasive endothelial function tests in the clinical phases of drug development in order to facilitate the development of drugs with safer cardiovascular profiles.

Complex anatomy making it difficult for left atrial appendage closure.

Left atrial appendage closure is a useful technique for patients at high thromboembolic risk and contraindications for oral anticoagulation therapy. However, it can be challenging when anatomical difficulties are encountered. We present a unique case of atypical appendage uptake and how we completed the procedure.

The 2011-2012 pilot European Society of Cardiology Sentinel Registry of Transcatheter Aortic Valve Implantation: 12-month clinical outcomes.

AIMS: Our aim was to assess one-year outcomes of patients enrolled in the pilot European Sentinel Registry of Transcatheter Aortic Valve Implantation (TAVI). METHODS AND RESULTS: One-year outcomes of 4,571 patients (81.4±7.2 years, 2,291 [50.1%] male) receiving TAVI with the SAPIEN XT (57.3%) or CoreValve prosthesis at 137 European centres were analysed using Kaplan-Meier and Cox proportional hazards regression techniques. At one year, 3,341 patients were alive, 821 had died, and 409 were lost to follow-up. Of 2,125 patients who underwent functional assessment, 1,916 (90%) were in New York Heart Association (NYHA) Class I/II at one year, with functional improvement from baseline noted in 1,682 patients (88%). One-year survival based on 4,564 patients was estimated at 79.1%. Independent baseline predictors of mortality were increasing age and logistic EuroSCORE, the presence of NYHA III/IV, chronic obstructive pulmonary disease, and atrial fibrillation. Female gender was associated with a 4% survival benefit at one year. Vascular access routes other than transfemoral were associated with poorer survival. Procedural failure and major periprocedural complications had an adverse impact on survival. CONCLUSIONS: Contemporary European experience attests to the effectiveness of routine TAVI in unselected elderly patients.

Extended use of the GuideLiner in complex coronary interventions.

AIMS: Challenging coronary anatomies including chronic total occlusions (CTO), extreme vessel tortuosity, diseased bypass grafts, and anomalous coronary arteries pose difficulties in coronary interventions. The GuideLiner is a monorail catheter originally developed to facilitate delivery of stents to target lesions in tortuous vessels. We conducted a study on the feasibility and safety of utilising this catheter in a wider array of complex coronary interventions. METHODS AND RESULTS: Consecutive patients undergoing coronary or peripheral interventions where a GuideLiner was used were recruited into this study. Patient demographics, lesion and vessel characteristics, procedural details and outcomes were prospectively entered into our database and analysed. From September 2009 to October 2011, 54 consecutive patients underwent coronary intervention in our institution using a GuideLiner; 21 out of 54 coronary applications were motivated by the need to increase support to cross CTOs, predominantly of the RCA. Anomalous or angulated take-off of the treatment vessels (31%), previously deployed proximal stents (15%), heavy proximal calcification (9%) and tortuosity (7%) accounted for the remaining reasons. One patient had successful renal denervation with the aid of a GuideLiner catheter. Procedural success was 98% in our series with no device-related periprocedural complications such as ostial dissection or myocardial necrosis. CONCLUSIONS: The use of a GuideLiner facilitates the approach to complex coronary interventions including chronic total occlusion and saphenous vein graft intervention by providing greater back-up support and easier engagement of coronary ostia.