Transcatheter aortic valve implantation amid the COVID-19 pandemic: a nationwide analysis of the first COVID-19 wave in the Netherlands.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on healthcare systems. Most transcatheter aortic valve implantation (TAVI) centres have adopted different triage systems and procedural strategies to serve highest-risk patients first and to minimise the burden on hospital logistics and personnel. We therefore assessed the impact of the COVID-19 pandemic on patient selection, type of anaesthesia and outcomes after TAVI. METHODS: We used data from the Netherlands Heart Registration to examine all patients who underwent TAVI between March 2020 and July 2020 (COVID cohort), and between March 2019 and July 2019 (pre-COVID cohort). We compared patient characteristics, procedural characteristics and clinical outcomes. RESULTS: We examined 2131 patients who underwent TAVI (1020 patients in COVID cohort, 1111 patients in pre-COVID cohort). EuroSCORE II was comparable between cohorts (COVID 4.5 ± 4.0 vs pre-COVID 4.6 ± 4.2, p = 0.356). The number of TAVI procedures under general anaesthesia was lower in the COVID cohort (35.2% vs 46.5%, p < 0.001). Incidences of stroke (COVID 2.7% vs pre-COVID 1.7%, p = 0.134), major vascular complications (2.3% vs 3.4%, p = 0.170) and permanent pacemaker implantation (10.0% vs 9.4%, p = 0.634) did not differ between cohorts. Thirty-day and 150-day mortality were comparable (2.8% vs 2.2%, p = 0.359 and 5.2% vs 5.2%, p = 0.993, respectively). CONCLUSIONS: During the COVID-19 pandemic, patient characteristics and outcomes after TAVI were not different than before the pandemic. This highlights the fact that TAVI procedures can be safely performed during the COVID-19 pandemic, without an increased risk of complications or mortality.

Update and, internal and temporal-validation of the FRANCE-2 and ACC-TAVI early-mortality prediction models for Transcatheter Aortic Valve Implantation (TAVI) using data from the Netherlands heart registration (NHR).

BACKGROUND: The predictive performance of the models FRANCE-2 and ACC-TAVI for early-mortality after Transcatheter Aortic Valve Implantation (TAVI) can decline over time and can be enhanced by updating them on new populations. We aim to update and internally and temporally validate these models using a recent TAVI-cohort from the Netherlands Heart Registration (NHR). METHODS: We used data of TAVI-patients treated in 2013-2017. For each original-model, the best update-method (model-intercept, model-recalibration, or model-revision) was selected by a closed-testing procedure. We internally validated both updated models with 1000 bootstrap samples. We also updated the models on the 2013-2016 dataset and temporally validated them on the 2017-dataset. Performance measures were the Area-Under ROC-curve (AU-ROC), Brier-score, and calibration graphs. RESULTS: We included 6177 TAVI-patients, with 4.5% observed early-mortality. The selected update-method for FRANCE-2 was model-intercept-update. Internal validation showed an AU-ROC of 0.63 (95%CI 0.62-0.66) and Brier-score of 0.04 (0.04-0.05). Calibration graphs show that it overestimates early-mortality. In temporal-validation, the AU-ROC was 0.61 (0.53-0.67).The selected update-method for ACC-TAVI was model-revision. In internal-validation, the AU-ROC was 0.63 (0.63-0.66) and Brier-score was 0.04 (0.04-0.05). The updated ACC-TAVI calibrates well up to a probability of 20%, and subsequently underestimates early-mortality. In temporal-validation the AU-ROC was 0.65 (0.58-0.72). CONCLUSION: Internal-validation of the updated models FRANCE-2 and ACC-TAVI with data from the NHR demonstrated improved performance, which was better than in external-validation studies and comparable to the original studies. In temporal-validation, ACC-TAVI outperformed FRANCE-2 because it suffered less from changes over time.

The impact of gender on long-term mortality in patients with multivessel disease after primary percutaneous coronary intervention.

BACKGROUND: Gender and complete revascularisation are known to affect mortality. The objective of this study was to analyse a gender difference in mortality with respect to complete revascularisation for multivessel disease after primary percutaneous coronary intervention (PPCI) in ST-elevation myocardial infarction (STEMI) patients. METHOD: In a prospective consecutive cohort of 1472 patients presenting with STEMI for PPCI, between January 2006 and January 2010, 832 patients with multivessel disease were analysed. The primary outcome was long-term mortality. RESULTS: Median follow-up was 3.3 ± 1.2 years. Complete revascularisation was performed less in females than in males (30 vs. 38 %; p = 0.04). At PPCI, women (27 %, n = 221) were ± 10 years older (p = 0.001), had more hypertension, renal failure and symptoms of heart failure (all p < 0.01). Cumulative long-term mortality with incomplete revascularisation was higher in females (F: 30 vs. M: 15 %, p = 0.01). After adjustment for baseline characteristics, complete revascularisation (0.84; 95 % CI 0.54-1.32) and gender (1.11; 95 % CI 0.73-1.69) lost significance. Also the gender-by-complete revascularisation interaction was not significant at long term. In women, age under 60 years independently predicted higher mortality (HR 10.09; 95 % CI 3.08-33.08; p < 0.001). CONCLUSION: In STEMI patients with multivessel disease at PPCI, women under the age of 60 years had higher mortality, but in women older than 60 years comorbidity impacted the outcome of revascularisation strategy in the long term.

The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty.

AIMS: The acute phase reactant C-reactive protein is an important prognostic risk factor in patients with both stable and unstable coronary artery disease. The potential prognostic implications of an abnormal pre-procedural C-reactive protein concentration in patients undergoing elective coronary angioplasty may be relevant for subsequent treatment. METHODS AND RESULTS: Pre-procedural plasma levels of C-reactive protein were measured in 501 patients with stable coronary artery disease undergoing elective coronary angioplasty. The incidence of death or myocardial infarction during a 2-year follow-up was 10.6% (24/227) in patients with an increased C-reactive protein level (>3 mg. l(-1)) and 2.9% (8/274) in patients with a normal C-reactive protein level (RR 3.9, 95% CI 1.7-8.9). Survival without death, myocardial infarction, urgent revascularization or hospital admission for unstable angina was significantly lower in patients with an increased C-reactive protein vs patients with a normal C-reactive protein (log-rank 14.62, P<0.0001). Logistic regression analysis identified an increased C-reactive protein level as a strong independent predictor of event-free survival (RR 2.54, 95% CI: 1.44-4.47, P=0.001). CONCLUSION: Pre-procedural C-reactive protein levels are increased in 45% of patients undergoing elective coronary angioplasty. An increased C-reactive protein level is a powerful independent prognostic indicator for subsequent cardiac events, suggesting that late clinical outcome is markedly influenced by pre-procedural systemic activation of inflammation.

Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestamibi single-photon emission computed tomography in patients with two-vessel coronary artery disease.

OBJECTIVES: We sought to perform a direct comparison between perfusion scintigraphic results and intracoronary-derived hemodynamic variables (fractional flow reserve [FFR]; absolute and relative coronary flow velocity reserve [CFVR and rCFVR, respectively]) in patients with two-vessel disease. BACKGROUND: There is limited information on the diagnostic accuracy of intracoronary-derived variables (CFVR, FFR and rCFVR) in patients with multivessel disease. METHODS: Dipyridamole technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT) was performed in 127 patients. The presence of reversible perfusion defects in the region of interest was determined. Within one week, angiography was performed; CFVR, rCFVR and FFR were determined in 161 coronary lesions after intracoronary administration of adenosine. The predictive value for the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR was evaluated by the area under the curve (AUC) of the receiver operating characteristics curves. RESULTS: The mean percentage diameter stenosis was 57% (range 35% to 85%), as measured by quantitative coronary angiography. Using per-patient analysis, the AUCs for CFVR (0.70 +/- 0.052), rCFVR (0.72 +/- 0.051) and FFR (0.76 +/- 0.050) were not significantly different (p = NS). The percentages of agreement with the results of MIBI SPECT were 76%, 78% and 77% for CFVR, rCFVR and FFR, respectively. Per-lesion analysis, using all 161 measured lesions, yielded similar results. CONCLUSIONS: The diagnostic accuracy of three intracoronary-derived hemodynamic variables, as compared with the results of perfusion scintigraphy, is similar in patients with two-vessel coronary artery disease. Cut-offvalues of 2.0 for CFVR, 0.65 for rCFVR and 0.75 for FFR can be used for clinical decision-making in this patient cohort. Discordant results were obtained in 23% of the cases that require prospective evaluation for appropriate patient management.

Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions.

BACKGROUND: Fractional flow reserve (FFR) and coronary blood flow velocity reserve (CFR) represent physiological quantities used to evaluate coronary lesion severity and to make clinical decisions. A comparison between the outcomes of both diagnostic techniques has not been performed in a large cohort of patients with intermediate coronary lesions. METHODS AND RESULTS: FFR and CFR were assessed in 126 consecutive patients with 150 intermediate coronary lesions (between 40% and 70% diameter stenosis by visual assessment). Agreement between outcomes of FFR and CFR, categorized at cut-off values of 0.75 and 2.0, respectively, was observed in 109 coronary lesions (73%), whereas discordant outcomes were present in 41 lesions (27%). In 26 of these 41 lesions, FFR was <0.75 and CFR>or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034). CONCLUSIONS: Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement.

Hyperemic coronary flow after optimized intravascular ultrasound-guided balloon angioplasty and stent implantation.

OBJECTIVES: This study evaluated the acute physiological gain of adjunctive intravascular ultrasound (IVUS) guided balloon angioplasty and stent implantation. BACKGROUND: Recent studies indicate safe coronary luminal enlargement and "stent-like" long-term outcomes using upsized balloons guided by IVUS. METHODS: After angiographically guided balloon angioplasty in 20 patients with 1-vessel disease and normal left ventricular function, IVUS was performed to determine the size of the adjunctive balloon using the mean of the maximal luminal diameter and the maximal diameter of the external elastic membrane measured in the adjacent proximal and distal reference segments. Serial adenosine-induced hyperemic blood flow velocity measurements were performed using a 0.014" Doppler guide wire to determine the physiological lumen obstruction after standard balloon angioplasty, followed by IVUS-guided balloon angioplasty and stent implantation. RESULTS: Upsized balloon angioplasty (increase balloon size: 0.98 +/- 0.26 mm; balloon:artery ratio 1.35 +/- 0.21) resulted in an additional increase of arterial dimensions: minimal lumen diameter (MLD) 2.18 +/- 0.38 mm to 2.73 +/- 0.51 mm; percent diameter stenosis (%DS) 34 +/- 13% to 19 +/- 22%; IVUS assessed minimal lumen area (MLA) 7.53 +/- 1.55 mm2 to 10.24 +/- 2.22 mm2 (all p < 0.0001). Major dissections (> or = type C) did not occur. Hyperemic blood flow velocity increased from 49.8 +/- 20.1 cm/s to 59.1 +/- 22.9 cm/s (p < 0.05) after IVUS-guided balloon angioplasty. Adjunctive stent implantation resulted in a further increase of MLD to 3.84 +/- 0.51 mm, %DS to -9 +/- 21% and MLA to 13.39 +/- 1.80 mm2 (all p < 0.0001), while hyperemic blood flow velocity remained unchanged (61.2 +/- 24.7 cm/s, p = 0.7). CONCLUSIONS: Upsized IVUS-guided balloon angioplasty increases arterial coronary dimensions and the distal hyperemic blood flow velocity. Adjunctive stent implantation does not yield a further gain in the hyperemic blood flow velocity, indicating the absence of a functional residual lumen obstruction after IVUS-guided balloon angioplasty. This may explain a similar clinical outcome reported after those coronary interventions.

Two hour ambulation after coronary angioplasty and stenting with 6 F guiding catheters and low dose heparin.

OBJECTIVE: To evaluate the feasibility and safety of ambulation of patients two hours after elective coronary angioplasty or stenting, or both. METHODS: Coronary angioplasty and stenting were performed using 6 F guiding catheters by the femoral approach and a standard dose of heparin 5000 IU. There were no angiographic exclusion criteria except for planned atherectomy. Patients given oral anticoagulants or heparin were not eligible. All patients were given aspirin. Patients who underwent stent implantation also received ticlopidine 250 mg daily. The arterial sheath was removed immediately after the procedure. Haemostasis was achieved by manual compression and maintained with an inguinal compression bandage. Early ambulation was attempted after two hours of supine bed rest following removal of the bandage. MAIN OUTCOME MEASURES: The incidence of bleeding at or during ambulation requiring compression and additional bed rest, and puncture site complications documented 48 hours after the procedure. RESULTS: 300 of 359 consecutive eligible patients were included for two hour ambulation. Stent implantation was performed in 32% of the procedures. The mean (SD) time to haemostasis was 9.6 (3.2) minutes. Bleeding at ambulation occurred in five patients (1.7%), and nine patients (3.0%) reached the secondary end point of haematoma > 5 x 5 cm at 48 hour follow up. All were treated conservatively without further sequelae. There was no late bleeding or vascular complications. CONCLUSION: Ambulation two hours after elective balloon angioplasty or stent implantation with 6 F guiding catheters by the femoral route and low dose heparin is feasible and safe, with a low incidence of puncture site complications. This early ambulation protocol facilitates a short hospital stay.

Quantification of collateral flow in humans: a comparison of angiographic, electrocardiographic and hemodynamic variables.

OBJECTIVES: Evaluation of collateral vascular circulation according to hemodynamic variables and its relation to myocardial ischemia. BACKGROUND: There is limited information regarding the hemodynamic quantification of recruitable collateral vessels. METHODS: Angiography of the donor coronary artery was performed before and during balloon coronary occlusion in 63 patients with one vessel disease. Patients were divided into groups of those with an absence of collateral vessels (group 1, n = 10), those with recruitable collateral vessels (group 2, n = 23) and those with spontaneously visible collateral vessels (group 3, n = 30). During balloon inflation the coronary wedge/aortic pressure ratio (Pw/Pao) was determined as were collateral blood flow velocity variables, using a 0.014" Doppler guide wire. Myocardial ischemia was defined as > or =0.1 mV ST-shift on a 12 lead electrocardiogram at 1 min coronary occlusion. RESULTS: Myocardial ischemia was present in all patients of group 1, in 14 patients of group 2 and in 3 patients of group 3. Recruitable collateral flow without ischemia showed similar hemodynamic values as in group 3 while these values were similar to group 1 in regard to the presence of recruitable collateral vessels showing ischemia. Logistic regression analysis revealed both Pw/Pao and Vi(col) as independent predictors for the function of collateral vessels. CONCLUSIONS: Hemodynamic variables of collateral vascular circulation are better markers of the functional significance of collateral vessels than is coronary angiography. The total collateral blood flow velocity integral and coronary wedge/aortic pressure ratio are good and independent predictors of the function of collateral vessels producing complementary information.

Sulfonylurea derivatives in cardiovascular research and in cardiovascular patients.

Sulfonylurea derivatives are hypoglycemic drugs frequently used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). In the beta-cell sulfonylureas act by blocking ATP-sensitive potassium channels (K.ATP channels). In several organ systems, including the cardiovascular system, sulfonylurea receptors and functional K.ATP channels have been identified. In the heart their role is not clear: an endogenous cardioprotective effect has been suggested. There is no doubt that K.ATP channels are effectively blocked by sulfonylureas. In the last decade sulfonylureas have been widely used as a pharmacological tool in experimental (cardiac) research. Blockade of K.ATP channels is the proposed cellular mechanism of action for all sulfonylurea-related effects. However, other membrane currents are affected as well. In addition, myocardial metabolism is modified by sulfonylurea pretreatment. Hence, it should seriously be questioned whether these drugs are suitable in assessing involvement of cardiac K.ATP channels in, for example, ischemia-related events. The detrimental effects of sulfonylureas in experimental studies on myocardial ischemia have led to speculation whether the widespread use of these drugs in patients with NIDDM, most often suffering from accompanying ischemic heart disease, should be reconsidered. However, a review of the clinical literature reveals that the most consistent finding is a lower incidence of ventricular arrhythmias associated with the use of glibenclamide, while no excess mortality has been shown for this agent in NIDDM with ischemic heart disease. Despite some direct effects on systemic and coronary vasculature, there are, at present, no firm clinical data on the basis of which sulfonylurea derivatives should be withheld from the cardiac patient.