Ticagrelor or Clopidogrel After an Acute Coronary Syndrome in the Elderly: A Propensity Score Matching Analysis from 16,653 Patients Treated with PCI Included in Two Large Multinational Registries.

PURPOSE: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population. METHODS: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients <75 versus ≥75 years old. Endpoints were BARC 3-5 MB, re-MI, and all-cause death at 1-year follow-up. The study included 16,653 patients (13,153 < 75 and 3500 ≥ 75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P < 0.001). Using propensity score matching (PSM), two treatment groups of 1566 patients were included in the final analysis. RESULTS: Ticagrelor was able to prevent re-MI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2-0.6; P < 0.001) and all-cause death (HR, 0.60; 95% CI, 0.4-0.9; P = 0.026) irrespective of age. In patients ≥75 years, ticagrelor reduced all-cause death (HR, 0.32; 95% CI, 0.1-0.8; P = 0.012) and re-MI (HR, 0.25; 95% CI, 0.1-1.1, P = 0.072). Moreover, even with the limit of the low number of events, ticagrelor did not significantly increase the incidence of MB (HR, 1.49; 95% CI, 0.70-3.0; P = 0.257). At multiple Cox regression, age (HR, 1.03; 95% CI, 1.02-1.05; P < 0.001) resulted an independent risk factor for bleeding. CONCLUSION: In our study, reflecting the results from two large retrospective, real-world registries, Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients with ACS treated with PCI, while significantly improving 1-year survival. Further studies on elderly patients are suggested.

Stent strut thickness and acute vessel injury during percutaneous coronary interventions: an optical coherence tomography randomized clinical trial.

AIMS: Compare the degree of acute vascular injury caused by a polymer-free, thin-strut drug-eluting stent (DES) to that caused by a bioresorbable polymer, thick-strut DES using optical coherence tomography (OCT). METHODS AND RESULTS: Fifty patients requiring nonurgent PCI were randomized to receive either a thin or a thick-strut DES. OCT was performed before and after stent implantation. OCT-based injury score (IS) after implantation was numerically higher within thick-strut stents 0.32 vs. 0.23, but the difference was NS (P = 0.61). Edge dissections were present in 36% of the patients without differences between groups. Tissue prolapse (TP) area was larger with thin-strut stents (2.26 vs. 1.83 mm2, P = 0.04). Stent expansion and symmetry index were similar between the two platforms (85% vs. 94%, P = 0.08; and 0.82 vs. 0.80, P = 0.25). No differences were observed in total malapposition area (1.85 mm2 in thin-strut stents vs. 1.47 mm2, P = 0.48). Regarding the influence of plaque-type, IS tended to be higher (non-significant) with thick strut DES in fibrocalcific plaques. Stent malapposition area was smaller in fibrous plaques, especially with thin strut stents (P = 0.03). CONCLUSION: There was no difference in the extent of OCT-based vessel injury associated with thin and thick-strut DES platforms. TP was larger with the thin strut DES, potentially reflecting a deeper stent embedment in the vessel wall.

Anatomical and functional healing after resorbable magnesium scaffold implantation in human coronary vessels: A combined optical coherence tomography and quantitative flow ratio analysis.

BACKGROUND: No data are currently available on the process of vessel healing and long-term physiological results after implantation of resorbable magnesium-made scaffold (RMS) in human coronary arteries. OBJECTIVES: To investigate after percutaneous coronary intervention (PCI) and at 12 months follow-up (a) RMS resorption process and vessel healing, as judged by optical coherence tomography (OCT) imaging; and (b) physiological result of RMS implantation evaluated by quantitative flow ratio (QFR). METHODS: All patients successfully treated with at least one RMS from July 2016 to August 2018 at 2 Italian centers were evaluated. All cases with OCT pullback and/or coronary angiography suitable for QFR analysis performed after PCI and at 12 months were included. Resorption process was analyzed at OCT in each frame reporting presence of residual struts in the vessel. RESULTS: Forty-four patients/forty-nine lesions were included. 12-months mean lumen area (LA; 7.54 ± 3.04 mm2 ) significantly decreased compared to mean LA recorded immediately after PCI (8.12 ± 1.89 mm2 ; p < .01). However, LA changes did not affect the functional result of PCI with a non-ischemic QFR value (>0.80) in 98% of cases at 12-months follow-up. Protruding struts were detectable in more than half of cases and their presence was correlated with an increase in mean LA (+0.73mm2 [95% CI 0.51-0.94], p < .001). CONCLUSIONS: RMS implantation in a real-world population lead to significant decrease in mean LA without significant functional impairment. Two different patterns of RMS resorption were recorded, whose clinical significance remains to be investigated.

Angiography-derived functional assessment of non-culprit coronary stenoses in primary percutaneous coronary intervention.

AIMS: Functional assessment of non-culprit lesions (NCL) in patients presenting with ST-elevation myocardial infarction (STEMI) and multivessel disease constitutes an unmet need. This study aimed to evaluate the diagnostic accuracy of quantitative flow ratio (QFR) in the functional assessment of NCL during the acute phase of STEMI. METHODS AND RESULTS: This was a retrospective, observational, multicentre study including patients with STEMI and staged fractional flow reserve (FFR) assessment of NCL. QFR in NCL was calculated from the coronary angiogram acquired during primary PCI in a blinded fashion with respect to FFR. The diagnostic value of QFR in the STEMI population was compared with a propensity score-matched population of stable angina patients. Eighty-two patients (91 NCL) were included. Target lesions were of both angiographic and functional (mean FFR 0.82±0.09) intermediate severity. The diagnostic performance of QFR was high (AUC 0.91 [95% CI: 0.85-0.97]) and similar to that observed in the matched control population (AUC 0.91 vs 0.94, p=0.5). The diagnostic accuracy of QFR was very high (>95%) in those vessels (61.5%) with QFR values out of a ROC-defined "grey zone" (0.75-0.85). A hybrid FFR/QFR approach (FFR only when QFR is in the grey zone) would adequately classify 96.7% of NCL, avoiding 58.5% of repeat diagnostic procedures. CONCLUSIONS: QFR has a good diagnostic accuracy in assessing the functional relevance of NCL during primary PCI, similar to the accuracy observed in stable patients.

Prediction of long-term patient outcome after contemporary left main stenting using the SYNTAX and SYNTAX II scores: A comparative analysis from the FAIL-II multicenter registry (failure in left main study with 2nd generation stents-Cardiogroup III study).

AIMS: To establish the value of the SYNTAX Score-II (SS-II) in predicting long-term mortality of patients treated with left main PCI (LM-PCI) using second-generation drug-eluting stents (DES). METHODS AND RESULTS: The SYNTAX score (SS) and the SS-II were calculated in 804 patients included in the FAILS-2 registry (failure in left main study with 2nd generation stents). Patients were classified in low (SS-II ≤33; n = 278, 34.6%), intermediate (SS-II 34-43; n = 260, 32.3%) and high (SS-II ≥44; n = 266, 33.1%) SS-II tertiles. Primary endpoint was all-cause mortality. A significant difference in long-term mortality was noted (5.2 ± 3.6 years): 4.1, 7.5, and 16.7% in low, mid and high SS-II tertiles respectively (p < .001). SS-II score was more accurate in predicting mortality than SS (AUC = 0.73; 95%CI: 0.67-0.79 vs. AUC = 0.55; 95%CI: 0.48-0.63, respectively; p < .001). SS-II led to a reclassification in the risk of all-cause mortality re-allocating 73% of patients from the CABG-only indication to PCI or equipoise PCI-or-CABG indication. Using multiple Cox regression analysis, SS-II (HR: 1.07; 95%CI: 1.05-1.09; p < .001), along with Acute coronary syndrome (ACS) (HR: 1.66; 95%CI: 1.03-2.66; p = .07) and Cardiogenic shock (CS) (HR: 2.82 (95%CI: 1.41-5.64; p = .003) were independent predictors of long-term mortality. SS-II (HR: 1.05; 95%CI: 1.04-1.06; p < .001) along with Insulin dependent Type 2 DM (HR: 1.58, 95%CI: 1.09-2.30.; p < .05), ACS (HR: 1.58, 95%CI: 1.16-2.14; p < .001) and CS (HR: 2.02 95%CI 1.16-3.53; p < .05), were independent predictors of long-term MACE. CONCLUSION: The SS-II was superior to the SS in predicting outcomes associated with contemporary LM-PCI. In this real-world population, two clinical variables not included in the SS-II, ACS and T2DM, were identified as additional markers of poor outcome.

Comprehensive physiological evaluation of epicardial and microvascular coronary domains using vascular conductance and zero flow pressure.

AIMS: Assessment of the coronary circulation has been based largely on pressure ratios (epicardial) and resistance (micro-vessels). Simultaneous assessment of epicardial (CEPI) and microvascular conductance (CMICRO) provides an intuitive approach using the same units for both coronary domains and expressing the actual deliverability of blood. The aim of this study was to develop a novel integral method for assessing the functional severity of epicardial and microvascular disease. METHODS AND RESULTS: We performed intracoronary pressure and Doppler flow velocity measurements in 403 vessels in 261 patients with stable coronary artery disease. Hyperaemic mid-to-late diastolic pressure and flow velocity (PV) relationships were calculated. The slope of the aortic PV indicates the overall conductance and the slope of the distal PV relationship represents CMICRO. The intercept with the x-axis represents zero-flow pressure (Pzf). CEPI was derived from microvascular and overall conductance. Median CEPI was higher compared to CMICRO (4.2 [2.1-8.0] versus 1.3 [1.0-1.7] cm/s/mmHg, p<0.001). CMICRO was independent of stenosis severity (1.3 [1.0-1.7] in FFR ≤0.80 versus 1.4 [1.0-1.8] in FFR >0.8, p=0.797). ROC curves (using FFR and HSR concordant vessels as standard) demonstrated an excellent ability of CEPI to characterise significant stenoses (AUC 0.93). When CEPI

Meta-Analysis Design and Results in Real Life: Problem Solvers or Detour to Maze. A Critical Review of Meta-Analysis of DAPT Randomized Controlled Trials.

BACKGROUND: Therapeutic strategies - such as duration of dual antiplatelet therapy after coronary artery stenting - usually generate a large quantity of meta-analyses. The meta-analyses that include the same randomized clinical trials should produce similar results. Our aim in the study is to analyze the quality and to compare the results of meta-analyses focused on a controversial topic such as dual antiplatelet therapy after percutaneous coronary intervention. METHODS: We searched all published meta-analyses published up to November 2015 (near DAPT trial publication) selecting those that included the same randomized clinical trials comparing patterns of briefer versus longer-term double antiplatelet therapy. RESULTS: Seventeen meta-analyses achieved our selection criteria. Of the seventeen analyzed, we identified seven (41.1%) based on the same ten randomized clinical trials (RCTs), yet their results varied widely. Many of the meta-analyses differed in only some minor aspect of the design (i.e. eligible studies, length of comparators and statistical methods used). Some authors differed in the number of patients participating in RCTs and even, despite reviewing the same underlying trials, only 2 of the 7 meta-analyses included the same number of patients. CONCLUSION: Meta-analyses around cardiovascular, all-cause or non-cardiovascular death differ frequently. In the DAPT duration setting, several meta-analyses have been recently published based on the same data, presenting several issues making it difficult to determine clear recommendations on certain points.

Safety of intermediate left main stenosis revascularization deferral based on fractional flow reserve and intravascular ultrasound: A systematic review and meta-regression including 908 deferred left main stenosis from 12 studies.

BACKGROUND: Current guidelines recommend intravascular ultrasound (IVUS) or fractional flow reserve (FFR) to decide upon ambiguous left main (LM) disease. However, no study has compared the safety of LM revascularization deferral based on FFR or IVUS. METHODS: MEDLINE/PubMed was systematically screened for studies reporting on deferred treatment of angiographically ambiguous LM based upon FFR or IVUS evaluation. Baseline, angiographic and outcome data were appraised and pooled separately for each strategy according to random-effect models with inverse-variance weighting. RESULTS: A total of 908 LM stenoses from 7 FFR and 5 IVUS studies were included with median follow-up of 29.0 and 31.5 months respectively. Per year of follow-up occurrence of overall MACE were 5.1% in FFR group and 6.4% in IVUS group while death, myocardial infarction, LM revascularization were respectively 2.6%, 1.5% and 1.8% vs. 3.0%, 0.5% and 2.2%. Meta-regression analysis suggested the influence of a distal LM stenosis on MACE in FFR group (ß = 0.06, p = 0.01) and age in IVUS group (ß = 0.4, p = 0.001). In individual studies several independent predictors of MACE were identified including use of lower doses of intracoronary adenosine (OR 1.39, p = 0.04) in FFR group and plaque burden (OR 1.34, p = 0.025), number of other diseased vessels (OR 1.39, p = 0.04) and any untreated stenosis (OR 3.80; p = 0.037) in IVUS- studies. CONCLUSIONS: Deferring LM intermediate stenosis on the basis of FFR or IVUS showed an acceptable and similar risk of events in a mid-term follow-up. Conversely, several different variables related to each technique showed an interaction on outcome.

Simplified hybrid algorithms for pressure wire interrogation exploiting advantages of a baseline and contrast Pd/Pa ratio indexes to predict stenosis significance: Insight from the SPARE multicenter prospective study.

BACKGROUND: Simplification of functional stenosis assessment with pressure guidewires may facilitate adoption of physiology-guided revascularization. An important step in this regard is the avoidance of hyperemic agents, required for fractional flow reserve (FFR) calculation. We evaluate the merits of a hybrid algorithms that combines the translesional pressure ratio (Pd/Pa) obtained at rest, after contrast medium injection (cFFR) and after adenosine administration (FFR). METHODS AND RESULTS: Eighty-six patients with 108 de novo intermediate coronary stenoses were included in this prospective, multicenter study. Using prespecified cut-off values that correctly identified stenosis with a 95% of agreement (<0.89 and >0.96 for Pd/Pa; <0.84 and > 0.87 for cFFR) we tested the efficiency of three different multi-step strategies combining the three indices to classify stenosis severity, using FFR-only measurement as reference. All three different hybrid algorithms (Pd/Pa-FFR; cFFR-FFR; Pd/Pa-cFFR-FFR) have more than 95% of agreement with FFR. Yet, the novel Pd/Pa-cFFR-FFR hybrid strategy demonstrated the best performance, avoiding the need of adenosine and medium contrast in 90% and 48% of cases, respectively. CONCLUSIONS: A hybrid Pd/Pa-cFFR-FFR decision-making algorithm could be an alternative and valuable strategy to increase the adoption of a physiology-guided PCI using conventional pressure guidewires and consoles.

Bifurcation Culprit Lesions in ST-segment Elevation Myocardial Infarction: Procedural Success and 5-year Outcome Compared With Nonbifurcation Lesions.

INTRODUCTION AND OBJECTIVES: We assessed short- and long-term outcomes of primary angioplasty in ST-segment elevation myocardial infarction by comparing bifurcation culprit lesions (BCL) with non-BCL. METHODS: Observational study with a propensity score matched control group. Among 2746 consecutive ST-segment elevation myocardial infarction patients, we found 274 (10%) patients with BCL. The primary outcome was a composite endpoint including all-cause death, myocardial infarction, coronary artery bypass grafting or target vessel revascularization, assessed at 30-days and 5-years. RESULTS: Baseline characteristics showed no differences after propensity matching (1:1). In the BCL group, the most frequent strategy was provisional stenting of the main branch (84%). Compared with the non-BCL group, the procedures were technically more complex in the BCL group in terms of need for balloon dilatation (71% BCL vs 59% non-BCL; P = .003), longer procedural time (70 ± 29minutes BCL vs 62.8 ± 28.9minutes non-BCL; P = .004) and contrast use (256.2 ± 87.9mL BCL vs 221.1 ± 82.3mL non-BCL; P < .001). Main branch angiographic success was similar (93.4% BCL vs 93.8% non-BCL; P = .86). Thirty-day all-cause mortality was similar between groups: 4.7% BCL vs 5.1% non-BCL; P = .84. At the 5-year follow-up, there were no differences in all-cause death (12% BCL vs 13% non-BCL; P = .95) or the combined event (22% BCL vs 21% non-BCL; P = .43). CONCLUSIONS: Primary angioplasty of a BCL was technically more complex; however, main branch angiographic success was similar, and there were no differences in long-term prognosis compared with non-BCL patients.

Significant Hemorrhage Rate Reduction after Gamma Knife Radiosurgery in Symptomatic Cavernous Malformations: Long-Term Outcome in 95 Case Series and Literature Review.

BACKGROUND: The natural history of cavernous malformations (CMs) has remained unclear. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery is nowadays controversial. The purpose of this paper is to throw light on the effectiveness of Gamma Knife radiosurgery (GKRS) therapy. METHODS: The authors reviewed data collected from a prospectively maintained database. A total of 95 patients (57 female and 38 male) underwent GKRS for high-surgical-risk CMs. A total of 76 cavernomas were deeply located (64 lesions in the brainstem and 12 lesions in the thalamus). All of them were located in eloquent regions. The median malformation volume was 1,570 mm3. The median tumor margin dose was 11.87 Gy, and the mean tumor maximum dose was 19.56 Gy. RESULTS: Ninety-five cavernous CMs were managed from 1994 to 2014. All patients had experienced at least 1 symptomatic bleeding incident before treatment (only 1 hemorrhage event in 81%). The median length of follow-up review was 78 months. The pretreatment annual hemorrhage rate was 3.06% compared with 1.4% during the first 3-year latency interval, and 0.16% thereafter (p = 0.004). Four patients developed new location-dependent neurological deficits, and 3 patients had edema-related headache after radiosurgery. All of them presented full recovery. CONCLUSIONS: The best dosage range for preventing bleeding was identified as between 11 and 12 Gy in our series. Although the efficacy of radiosurgery in CMs remains impossible to quantify, a very significant reduction in the bleeding rate occurs after a 3-year latency interval. No permanent neurological morbidity is reported in our series. These results defend the safety of GKRS in surgical high-risk CM from the first bleeding event.

Influence of the amount of myocardium subtended to a coronary stenosis on the index of microcirculatory resistance. Implications for the invasive assessment of microcirculatory function in ischaemic heart disease.

AIMS: The index of microcirculatory resistance (IMR) is increasingly used to quantify microcirculatory function. However, in normal coronary arteries, resistance increases with the branching structure of the coronary tree, which suggests that IMR could be influenced by the amount of downstream myocardial mass (MM). We aimed to evaluate the influence of the amount of MM subtended to an intermediate stenosis on the IMR. METHODS AND RESULTS: IMR, fractional flow reserve and coronary flow reserve (CFR) were measured in 123 coronary arteries (102 patients) with intermediate stenosis. Jeopardised MM was estimated with the Myocardial Jeopardy Index (MJI). MM was inversely associated with IMR (R.

Determinants of percutaneous coronary intervention success in repeat chronic total occlusion procedures following an initial failed attempt.

AIM: To investigate the rates and determinants of success of repeat percutaneous coronary intervention (PCI) following an initial failed attempt at recanalising the chronic total occlusions (CTO) percutaneously. METHODS: In 445 consecutive first attempt CTO-PCI procedures in our institution, procedural failure occurred in 149 (33.5%). Sixty-four re-PCI procedures were performed in 58 patients (39%) all had a single CTO. Procedural and outcome data in the re-PCI population was entered into the institutional database. A retrospective analysis of clinical, angiographic and procedural data was performed. RESULTS: Procedural success was achieved in 41 (64%) procedures. Univariate analysis of clinical and angiographic characteristics showed that re-PCI success was associated with intravascular ultrasound (IVUS) guidance (19.5% vs 0%, P = 0.042), while failure was associated with severe calcification (30.4% vs 9.7%, P = 0.047) and a JCTO score > 3 (56.5% vs 17.1% P = 0.003). Following multiple regression analysis the degree of lesion complexity (J-CTO score > 3), IVUS use, involvement of an experienced CTO operator and LAD CTO location were significant predictors of successful re-PCI. Overall the complication rate was low, with the only MACCE two periprocedural MI's neither of which required intervention. CONCLUSION: Re-PCI substantially increases the overall success rate of CTO revascularization. Predictors of re-PCI success included the use of IVUS, the involvement of an experienced CTO operator in the repeat attempt and the location of the CTO.

PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor (PREDICT): study rationale and design. A randomized multicenter clinical trial using intracoronary multimodal physiology.

BACKGROUND: In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects. METHODS: PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect). CONCLUSIONS: PREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI ( http://www.clinicaltrials.gov No. NCT02698618).

Combining Baseline Distal-to-Aortic Pressure Ratio and Fractional Flow Reserve in the Assessment of Coronary Stenosis Severity.

OBJECTIVES: This study sought to understand the physiological basis of baseline distal-to-aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) agreement and discordance, using coronary flow reserve (CFR), stenosis resistance, and microcirculatory resistance measurements, and form there, to investigate the potential value of combining Pd/Pa with FFR in the diagnostic rationale. BACKGROUND: Pd/Pa is always available before FFR assessment, and emerging data supports the notion that baseline indices can determine the ischemic potential of coronary stenosis in selected subsets. METHODS: A total of 467 stenosed vessels from 363 patients were investigated with pressure and flow sensors during baseline and hyperemia: 168 vessels (135 patients) with thermodilution-derived flow, and 299 vessels (228 patients) with Doppler-derived flow. RESULTS: Pd/Pa correlated more strongly with CFR than FFR (ρ difference = 0.129; p for ρ comparison <0.001). Although Pd/Pa and FFR were closely correlated (ρ = 0.798; 95% confidence interval: 0.767 to 0.828), categorical discordance was observed in 19.3% of total vessels. Such discordance was associated with the patients' clinical profile and was characterized by contrastive changes in stenosis resistance, microcirculatory resistance, and the underlying CFR. Notably, all stenosis with Pd/Pa ≤0.83 (n = 74, 15.8%) progressed to FFR ≤0.80, and although no Pd/Pa cutoff was able to exclude the development of FFR ≤0.80 in the high end of values, only 15 (10.1%) vessels with Pd/Pa ≥0.96 (n = 149, 31.9%) developed FFR ≤0.80, from which none had definite ischemia, as defined by CFR ≤1.74. CONCLUSIONS: Combining baseline Pd/Pa with FFR seems to provide a more comprehensive physiological examination of stenosed coronary arteries and a closer pressure-based appraisal of the flow reserve of the downstream myocardial bed.

Incidence, Causes, and Predictors of Early (≤30 Days) and Late Unplanned Hospital Readmissions After Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to determine the incidence, causes, and predictors of unplanned hospital readmissions after transcatheter aortic valve replacement (TAVR). BACKGROUND: Data regarding unplanned hospital readmissions after TAVR in a real-world all-comers population are scarce. METHODS: A total of 720 consecutive patients undergoing TAVR at 2 centers who survived the procedure, were included. Median follow-up was 23 months (interquartile range [IQR]: 12 to 39 months), available in 99.9% of the initial population. The occurrence, timing, and causes of hospital readmission within the first year post-TAVR were obtained in all cases. Early and late readmissions were defined as those occurring ≤30 days and >30 days to 1 year post-TAVR, respectively. RESULTS: There were 506 unplanned readmissions in 316 patients (43.9%) within the first year post-TAVR (median time: 63 days; IQR: 19 to 158 days post-discharge). Of these, early readmission occurred in 105 patients (14.6%), and 118 patients (16.4%) had multiple (≥2) readmissions. Readmissions were due to noncardiac and cardiac causes in 59% and 41% of cases, respectively. Noncardiac readmissions included, in order of decreasing frequency, respiratory, infection, and bleeding events as the main causes, whereas heart failure and arrhythmias accounted for most cardiac readmissions. The predictors of early readmission were periprocedural major bleeding complications (p = 0.001), anemia (p = 0.019), lower left ventricular ejection fraction (p = 0.042), and the combined presence of antiplatelet and anticoagulation therapy at hospital discharge (p = 0.014). The predictors of late readmission were chronic obstructive pulmonary disease (p = 0.001), peripheral vascular disease (p = 0.023), chronic renal failure (p = 0.013), and atrial fibrillation (p = 0.012). Early readmission was an independent predictor of mortality during the follow-up period (hazard ratio: 1.56, 95% confidence interval: 1.02 to 2.39, p = 0.043). CONCLUSIONS: The readmission burden after TAVR in an all-comers population was high. Nearly one-fifth of the patients were readmitted early after hospital discharge, increasing the risk of mortality at follow-up. Reasons for readmission were split between noncardiac and cardiac causes, with respiratory causes and heart failure as the main diagnoses in each group, respectively. Whereas early readmissions were mainly related to periprocedural bleeding events, most late readmissions were secondary to baseline patient comorbidities. These results underscore the importance of and provide the basis for implementing specific preventive measures to reduce readmission rates after TAVR.

Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention.

BACKGROUND: A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). METHODS AND RESULTS: Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H2 (15)O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H2 (15)O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). CONCLUSIONS: Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow. CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier: NTR3164.