iFR/FFR/IVUS Discordance and Clinical Implications: Results From the Prospective Left Main Physiology Registry.

OBJECTIVES: This study aimed to assess discordance between results of instantaneous wave-free ratio (iFR), fractional flow reserve (FFR), and intravascular ultrasound (IVUS) in intermediate left main coronary (LM) lesions, and its impact on clinical decision making and outcome. METHODS: We enrolled 250 patients with a 40%-80% LM stenosis in a prospective, multicenter registry. These patients underwent both iFR and FFR measurements. Of these, 86 underwent IVUS and assessment of the minimal lumen area (MLA), with a 6 mm2 cutoff for significance. RESULTS: Isolated LM disease was recognized in 95 patients (38.0%), while 155 patients (62.0%) had both LM disease and downstream disease. In 53.2% of iFR+ and 56.7% of FFR+ LM lesions, the measurement was positive in only one daughter vessel. iFR/FFR discordance occurred in 25.0% of patients with isolated LM disease and 36.2% of patients with concomitant downstream disease (P=.049). In patients with isolated LM disease, discordance was significantly more common in the left anterior descending artery and younger age was an independent predictor of iFR-/FFR+ discordance. iFR/MLA and FFR/MLA discordance occurred in 37.0% and 29.4%, respectively. Within 1 year of follow-up, major cardiac adverse events (MACE) occurred in 8.5% and 9.7% (P=.763) of patients whose LM lesion was deferred or revascularized, respectively. Discordance was not an independent predictor of MACE. CONCLUSIONS: Current methods of estimating LM lesion significance often yield discrepant findings, complicating therapeutic decision-making.

Mortality in STEMI Patients With Cardiogenic Shock: Results From a Nationwide PCI Registry and Focus on Left Main PCI.

BACKGROUND: The study aims to assess real-life short- and long-term outcomes of patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) complicated with cardiogenic shock (CS). Outcome after left main (LM) PCI is of particular interest. METHODS: Procedural, 30-day, and >30-day mortality rates were assessed in 2744 CS-STEMI patients enrolled between 2012 and 2019 in a nationwide registry involving 49 centers. RESULTS: Procedural, 30-day, and >30-day mortality rates were 6.9%, 39.8%, and 12.6%, respectively. The mortality rates were significantly higher in the 348 patients (12.7%) who underwent LM-PCI (13.5%, 59.5%, and 18.4%, respectively). LM-PCI, a suboptimal PCI result, and transfemoral access were independent predictors of procedural and 30-day mortality. Operator experience was an independent predictor of procedural mortality, but not 30-day mortality. CONCLUSIONS: Mortality remains high in CS-STEMI patients, especially within the first month. Patients undergoing LM-PCI are particularly at risk. Operator experience is predictive of procedural mortality.

Practice and long-term outcome of unprotected left main PCI: real-world data from a nationwide registry.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly performed in significant left main (LM) lesions. Left untreated, the prognosis is poor, but PCI and coronary bypass surgery (CABG) behold risks as well. Additional long-term outcome data might guide future treatment decisions. METHODS: Between 2012 and 2019, all 6783 patients who underwent LM PCI were prospectively enrolled in a national registry. Patients with prior CABG or prior LM PCI, and patients presenting in cardiogenic shock or after out-of-hospital cardiac arrest were excluded. From the remaining 5284 patients, baseline and procedural data as well as long-term survival were assessed. RESULTS: The annual rate of LM PCI increased from 422 (2.2% of PCIs) in 2012 to 868 in 2018 (3.0%). By 2018, 71% of the interventional cardiologists performed at least 1 LM PCI a year, though only 5 on average. Use of transradial access (TRA) in LM PCI increased from 20.4% in 2012 to 59.5% in 2019. All-cause mortality was 6.0% at 30 days and 18.5% at a mean follow-up of 33.5 months. Independent predictors of higher long-term mortality were older age, diabetes, multivessel disease, an urgent indication, a suboptimal angiographical result, and non-exclusive use of drug-eluting stents. TRAand higher operator and centre LM PCI experience were independent predictors of a lower long-term mortality. CONCLUSION: LM PCI is associated with high short- and long-term mortality. Use of TRA and higher expertise in LM PCI were associated with better survival.

Clinical validation of a 13-lead electrocardiogram derived from a self-applicable 3-lead recording for diagnosis of myocardial supply ischaemia and common non-ischaemic electrocardiogram abnormalities at rest.

Aims: In this study, we compare the diagnostic accuracy of a standard 12-lead electrocardiogram (ECG) with a novel 13-lead ECG derived from a self-applicable 3-lead ECG recorded with the right exploratory left foot (RELF) device. The 13th lead is a novel age and sex orthonormalized computed ST (ASO-ST) lead to increase the sensitivity for detecting ischaemia during acute coronary artery occlusion. Methods and results: A database of simultaneously recorded 12-lead ECGs and RELF recordings from 110 patients undergoing coronary angioplasty and 30 healthy subjects was used. Five cardiologists scored the learning data set and five other cardiologists scored the validation data set. In addition, the presence of non-ischaemic ECG abnormalities was compared. The accuracy for detection of myocardial supply ischaemia with the derived 12 leads was comparable with that of the standard 12-lead ECG (P = 0.126). By adding the ASO-ST lead, the accuracy increased to 77.4% [95% confidence interval (CI): 72.4-82.3; P < 0.001], which was attributed to a higher sensitivity of 81.9% (95% CI: 74.8-89.1) for the RELF 13-lead ECG compared with a sensitivity of 76.8% (95% CI: 71.9-81.7; P < 0.001) for the 12-lead ECG. There was no significant difference in the diagnosis of non-ischaemic ECG abnormalities, except for Q-waves that were more frequently detected on the standard ECG compared with the derived ECG (25.9 vs. 13.8%; P < 0.001). Conclusion: A self-applicable and easy-to-use 3-lead RELF device can compute a 12-lead ECG plus an ischaemia-specific 13th lead that is, compared with the standard 12-lead ECG, more accurate for the visual diagnosis of myocardial supply ischaemia by cardiologists.

Physiology-Based Revascularization of Left Main Coronary Artery Disease.

It is of critical importance to correctly assess the significance of a left main lesion. Underestimation of significance beholds the risk of inappropriate deferral of revascularization, whereas overestimation may trigger major but unnecessary interventions. This article addresses the invasive physiological assessment of left main disease and its role in deciding upon revascularization. It mainly focuses on the available evidence for fractional flow reserve and instantaneous wave-free ratio, their interpretation, and limitations. We also discuss alternative invasive physiological indices and imaging, as well as the link between physiology, ischemia, and prognosis.

iFR uncovers profound but mostly reversible ischemia in CTOs and helps to optimize PCI results.

OBJECTIVES: The study aimed to demonstrate through instant wave-free ratio (iFR) measurements that myocardium distal to a chronic total occlusion (CTO) is ischemic, that ischemia is reversible by PCI, and that iFR assessment after PCI can be used to optimize PCI results. BACKGROUND: The greatest benefit of revascularization is found in patients with low fractional flow reserve. In patients with CTOs, iFR measurement may be more appropriate to evaluate ischemia as it does not require maximal microvascular vasodilation, which may be hampered by microvascular dysfunction. METHODS: The iFR was measured in 81 CTO patients, both pre- and post-PCI in 63 patients, and only post-PCI in the following 18 patients. A pressure wire pullback was performed post-PCI if iFR ≤0.89. RESULTS: The first 63 patients all had significant ischemia distal to the CTO with a median iFR of 0.33 [0.22; 0.44], improving significantly post-PCI to a median iFR of 0.93 [0.89;0.96] (p < .001). In the complete cohort, the median iFR post-PCI was 0.93 [0.86;0.96] but still ≤0.89 in 23 patients (30%). 12 of these patients had further PCI optimization because of a residual focal pressure gradient on pullback, after which only two had a final iFR ≤0.89. CONCLUSIONS: In CTO patients with an indication for PCI, iFR consistently demonstrated profound myocardial ischemia. Successful PCI immediately relieved ischemia in 70% of patients. In the remaining 30% of cases, a manual iFR pullback proved helpful in guiding further optimization of the PCI result.

Different dynamics of new-onset electrocardiographic changes after balloon- and self-expandable transcatheter aortic valve replacement: Implications for prolonged heart rhythm monitoring.

BACKGROUND: New onset electrocardiographic (ECG) changes after transcatheter aortic valve replacement (TAVR) are used to assess the risk for late atrioventricular block. However, the time of ECG evaluation remains controversial. We aimed to compare the time course and dynamics of new onset ECG changes according to valve design in balloon- (BEV) and self-expandable (SEV) TAVR. METHODS AND RESULTS: This single center study enrolled 133 consecutive TAVR patients (28.6% SEV, 71.4% BEV). Patients with pre-existent permanent pacemaker implant (PPMI), procedural death or incomplete ECG registration were excluded. Standard 12­lead ECG was performed before the procedure, at 1, 24, 48 and 120 h and 1 month. In BEV patients, no significant PR prolongation occurred, whereas in SEV patients the PR interval prolonged significantly with 33.7 ± 22.0 ms (p < 0.001, compared to pre-TAVR) but only after 48 h after TAVR. Widening of QRS duration was comparable among both BEV and SEV patients (6.7 ± 21.5 versus 17.0 ± 26.9 ms, p = 0.061) and occurred immediately after TAVR. New-onset left bundle branch block was seen in 18.5% of BEV and 30.8% of SEV patients (p = 0.120) and occurred within 24 h after TAVR in both groups. Late PPMI (>24 h after TAVR) was higher in SEV compared to BEV patients (15.3% versus 1.5%, p = 0.008). CONCLUSION: Self-expandable valves cause more impairment in atrioventricular conduction with a delayed time course compared to balloon expandable valves. This might explain the higher pacemaker need beyond 24 h after TAVR. Our findings suggest that patients with self-expandable valves require at least 48 h ECG monitoring post TAVR.

Septal flash is a prevalent and early dyssynchrony marker in transcatheter aortic valve replacement-induced left bundle branch block.

New-onset left bundle branch block (LBBB) is a frequent complication after transcatheter aortic valve replacement (TAVR) and provides an opportunity to study dyssynchrony immediately following acute LBBB. This study aims to (1) assess echocardiographic dyssynchrony in acute TAVR-induced LBBB (TAVR-LBBB), and (2) compare dyssynchrony parameters among different patient groups with LBBB. The study enrolled all TAVR-LBBB patients at Ghent University Hospital between 2013 and 2019. First, acute TAVR-LBBB dyssynchrony was assessed by: (1) septal flash (SF); (2) interventricular mechanical delay (IVMD; cut-off ≥ 40 ms) and (3) presence of 'classical dyssynchronous strain pattern' assessed with speckle tracking. Secondly, acute TAVR-LBBB patients with SF (LBBBTAVR+SF) were compared to randomly selected LBBB-SF patients with preserved (LBBBSF+PEF) ànd reduced ejection fraction (LBBBSF+REF). In TAVR-LBBB patients (n = 25), SF was detected in 72% of patients, whereas only 5% of TAVR-LBBB patients showed a classical dyssynchronous strain pattern. IVMD in these TAVR-LBBB patients was 39 ms. In 90% of LBBBTAVR+SF patients, SF was observed within 24 h after LBBB onset. Among LBBB-SF patients, a classical strain pattern was more prevalent in LBBBSF+REF patients compared to LBBBTAVR+SF patients (80% vs. 7%; p < 0.001). IVMD was significantly longer in LBBBSF+PEF patients (52 ms; p = 0.002) and LBBBSF+REF patients (57 ms; p = 0.009) compared to LBBBTAVR+SF patients (37 ms). SF is an early and prevalent marker of LV dyssynchrony in acute TAVR-LBBB, whereas strain-based measures and IVMD do not appear to capture dyssynchrony at this early stage. Our findings from the comparative analysis generate the hypothesis that progressive LBBB-induced LV remodeling may be required for a 'classical dyssynchrony strain pattern' or significant IVMD to occur in TAVR-LBBB patients.

Feasibility of His-bundle pacing in patients with conduction disorders following transcatheter aortic valve replacement.

BACKGROUND: Conduction disorders requiring permanent pacemaker implantation occur frequently after transcatheter aortic valve replacement (TAVR). This multicenter study explored the feasibility and safety of His bundle pacing (HBP) in TAVR patients with a pacemaker indication to correct a TAVR-induced left bundle branch block (LBBB). METHODS: Patients qualifying for a permanent pacemaker implant after TAVR were planned for HBP implant. HBP was performed using the Select Secure (3830; Medtronic) pacing lead, delivered through a fixed curve or deflectable sheath (C315HIS or C304; Medtronic). Successful HBP was defined as selective or nonselective HBP, irrespective of LBB recruitment. Successful LBBB correction was defined as selective or nonselective HBP resulting in paced QRS morphology similar to pre-TAVR QRS and paced QRS duration (QRSd) less than 120 milliseconds with thresholds less than 3.0 V at 1.0-millisecond pulse width. RESULTS: The study enrolled 16 patients requiring a permanent pacemaker after TAVR (age 85 ± 4 years, 31% female, all LBBB; QRSd: 161 ± 14 milliseconds). Capture of the His bundle was achieved in 13 of 16 (81%) patients. HBP with LBBB correction was achieved in 11 of 16 (69%) and QRSd narrowed from 162 ± 14 to 99 ± 13 milliseconds and 134 ± 7 milliseconds during S-HBP and NS-HBP, respectively (P = .005). At implantation, mean threshold for LBBB correction was 1.9 ± 1.1 V at 1.0 millisecond. Thresholds remained stable at 11 ± 4 months follow-up (1.8 ± 0.9 V at 1.0 millisecond, P = .231 for comparison with implant thresholds). During HBP implant, one temporary complete atrioventricular block occurred. CONCLUSION: Permanent HBP is feasible in the majority of patients with TAVR requiring a permanent pacemaker with the potential to correct a TAVR-induced LBBB with acceptable pacing thresholds.

Spontaneous coronary artery dissection in a patient with hereditary polycystic kidney disease and a recent liver transplant: a case report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an underestimated cause of acute coronary syndromes. A predisposing arteriopathy is often present and a stressor can sometimes be identified. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder; its associated arteriopathy has been described as a predisposing condition for SCAD. CASE SUMMARY: A 44-year-old woman with ADPKD presented in the emergency room with recent onset thoracic pain radiating to the left arm at rest. She had undergone a recent liver transplant, for which she had received high-dose corticosteroids during 1 month. She was still taking tacrolimus and mycophenolate mofetil. She had no traditional risk factors but had experienced stress postoperatively. She was known with moderate chronic kidney disease. The initial electrocardiogram (ECG) was normal but high-sensitive troponin T was significantly elevated. Coronary angiography demonstrated diffuse narrowing of the distal left anterior descending artery with preserved flow, compatible with a SCAD Type 2 that was treated conservatively. However, under dual antiplatelet therapy (DAPT) with clopidogrel, the coronary dissection was progressive with new ischaemic ECG changes, further rise of troponins and development of apicoseptal hypokinesia. Because of the small vessel diameter and the preserved distal flow, conservative treatment was maintained. Clopidogrel was interrupted and the patient remained stable. DISCUSSION: As SCAD remains an underestimated cause of myocardial infarction, clinicians should be aware of the possibility of SCAD in ADPKD patients with chest pain. This case report illustrates that the decision DAPT vs. aspirin should be individualized in these patients.

Feasibility and performance of a device for automatic self-detection of symptomatic acute coronary artery occlusion in outpatients with coronary artery disease: a multicentre observational study.

BACKGROUND: Time delay between onset of symptoms and seeking medical attention is a major determinant of mortality and morbidity in patients with acute coronary artery occlusion. Response time might be reduced by reliable self-detection. We aimed to formally assess the proof-of-concept and accuracy of self-detection of acute coronary artery occlusion by patients during daily life situations and during the very early stages of acute coronary artery occlusion. METHODS: In this multicentre, observational study, we tested the operational feasibility, specificity, and sensitivity of our RELF method, a three-lead detection system with an automatic algorithm built into a mobile handheld device, for detection of acute coronary artery occlusion. Patients were recruited continuously by physician referrals from three Belgian hospitals until the desired sample size was achieved, had been discharged with planned elective percutaneous coronary intervention, and were able to use a smartphone; they were asked to perform random ambulatory self-recordings for at least 1 week. A similar self-recording was made before percutaneous coronary intervention and at 60 s of balloon occlusion. Patients were clinically followed up until 1 month after discharge. We quantitatively assessed the operational feasibility with an automated dichotomous quality check of self-recordings. Performance was assessed by analysing the receiver operator characteristics of the ST difference vector magnitude. This trial is registered with ClinicalTrials.gov, number NCT02983396. FINDINGS: From Nov 18, 2016, to April 25, 2018, we enrolled 64 patients into the study, of whom 59 (92%) were eligible for self-applications. 58 (91%) of 64 (95% CI 81·0-95·6) patients were able to perform ambulatory self-recordings. Of all 5011 self-recordings, 4567 (91%) were automatically classified as successful within 1 min. In 65 balloon occlusions, 63 index tests at 60 s of occlusion in 55 patients were available. The mean specificity of daily life recordings was 0·96 (0·95-0·97). The mean false positive rate during daily life conditions was 4·19% (95% CI 3·29-5·10). The sensitivity for the target conditions was 0·87 (55 of 63; 95% CI 0·77-0·93) for acute coronary artery occlusion, 0·95 (54 of 57; 0·86-0·98) for acute coronary artery occlusion with electrocardiogram (ECG) changes, and 1·00 (35 of 35) for acute coronary artery occlusion with ECG changes and ST-segment elevation myocardial infarction criteria (STEMI). The index test was more sensitive to detect a 60 s balloon occlusion than the STEMI criteria on 12-lead ECG (87% vs 56%; p<0·0001). The proportion of total variation in study estimates due to heterogeneity between patients (I2) was low (12·6%). The area under the receiver operator characteristics curve was 0·973 (95% CI 0·956-0·990) for acute coronary artery occlusion at different cutoff values of the magnitude of the ST difference vector. No patients died during the study. INTERPRETATION: Self-recording with our RELF device is feasible for most patients with coronary artery disease. The sensitivity and specificity for automatic detection of the earliest phase of acute coronary artery occlusion support the concept of our RELF device for patient empowerment to reduce delay and increase Survival without overloading emergency services. FUNDING: Ghent University, Industrial Research Fund.

'CLOSE'-Guided Pulmonary Vein Isolation and Changes in Local Bipolar and Unipolar Atrial Electrograms: Observations from the EP Lab.

BACKGROUND: 'CLOSE'-guided pulmonary vein isolation (PVI) is a point-by-point, contact force (CF)-guided radiofrequency (RF) approach aiming to enclose the PVs with contiguous RF lesions by targeting strict criteria for interlesion distance and ablation index (AI). We characterized real-time changes in bipolar (B-EGMs) and unipolar electrograms (U-EGMs) during AI-targeted RF delivery. METHODS: EGM changes during 56 RF applications in 7 patients with paroxysmal atrial fibrillation (AF) undergoing 'CLOSE'-guided PVI were studied. CF-guided RF was delivered with 35W targeting an AI of 400 at posterior and 550 at anterior wall. 336 B-EGMs and 336 U-EGMs before, during and after RF delivery were analyzed with their RF characteristics. Amplitude of the B-and U-EGM and morphology of the U-EGM were measured at each 5-second step using custom-made software. RESULTS: We observed a significant reduction in B-EGM amplitude (0.43 [IQR=0.25, 0.55] to 0.11 [0.07, 0.22] mV, p<0.001) and U-EGM amplitude (0.57 [0.40, 0.87] to 0.22 [0.10, 0.34] mV, p<0.001) within 5 seconds, after which no more changes were observed. Impedance drop was 18.3±1.1Ω. Loss of the unipolar terminal S-wave occurred in 59% of applications. There was no correlation between U-EGM morphology changes and RF characteristics. CONCLUSION: In AI-guided RF delivery there is a significant reduction in EGM amplitude within 5 seconds. Loss of the unipolar terminal S wave occurred in 59% of applications and was not related to RF characteristics suggestive of adequate lesion formation. These findings suggest that there is a limited value in monitoring electrograms to further optimize 'CLOSE'-guided PVI.

A happy valve in a happy patient? Serotonergic antidepressants and the risk of valvular heart disease (SERVAL). A case-control study.

OBJECTIVES: The objective was to investigate the risk of valvular heart disease in humans in relation to the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors. DESIGN: A case-control study. We conducted a case-control study within this cohort in which patients with newly diagnosed cardiac valve regurgitation were age-matched to controls. Patient demographics, their cardiovascular risk factors and medication use were extracted in both series. Use of SSRIs, serotonin and noradreline reuptake inhibitors (SNRIs) and other pro-serotonergic agents, their dose and treatment duration were recorded. Logistic regression analysis was used to establish the strength of the association between SSRI/SNRI use and valvular heart disease. SETTING: Outpatient clinic of the cardiology department at the Ghent University Hospital, East-Flanders in Belgium. PARTICIPANTS: Total of 2911 persons 21-58 years of age who had undergone an echocardiogram in the period 2006-2010 and had no known cardiovascular disease or previous cardiac intervention. Two hundred and six echocardiographically proven cases of valvular regurgitation and 195 matched controls. MAIN OUTCOME MEASURE: Odd ratio of valvular disease associated with intake of serotonergic drugs. RESULTS: Of the 206 patients with newly diagnosed cardiac valve regurgitation, 11.6% were exposed to serotonergic agents compared to 4.1% in the 195 control patients, leading to an odds ratio of 3.08 (95% confidence interval [CI] 1.35-7.04). The analysis of doses and treatment durations revealed a dose-relationship pattern between SSRI/SNRI use and prevalent valvular heart disease. CONCLUSIONS: In this study, use of serotonergic antidepressants was associated with an increased rate of valvular regurgitation in humans.

Neomacrolides in the treatment of patients with severe asthma and/or bronchiectasis: a retrospective observational study.

RATIONALE: Previous studies have demonstrated that long-term low-dose macrolides are efficacious in cystic fibrosis (CF) and diffuse panbronchiolitis, two chronic neutrophilic airway diseases. AIMS: The aims of this study were to evaluate the efficacy and safety of low-dose neomacrolides as add-on therapy in patients with severe asthma and/or bronchiectasis and to identify predictors for therapeutic response. METHODS: In a retrospective observational cohort study, we examined 131 adult, non-CF patients with severe asthma and/or bronchiectasis, receiving low-dose neomacrolides as add-on treatment. Pulmonary function tests and symptom scores were assessed at baseline and after 3 to 8 weeks of therapy. RESULTS: After 3-8 weeks of treatment with low-dose neomacrolides, 108 patients were available for evaluation. In asthma patients (n = 47), pulmonary function tests and symptom scores improved significantly. Responders (≥7% forced expiratory volume in one second predicted [FEV(1)%] improvement) were older (55 vs. 47 years; p = 0.042) and had a longer duration of asthma (29 vs. 9 years; p = 0.052). In patients with bronchiectasis only (n = 61), symptom scores improved significantly. Responders (≥60% symptom score improvement) were older (61 vs. 53 years; p = 0.004), more frequently male (53% vs. 27%; p = 0.043), and there was a nonsignificant trend towards higher high-resolution CT (HRCT) score for bronchiectasis in responders (6.4 vs. 4.6; p = 0.053). In multivariate logistic regression analysis, age and male gender were independent predictors for improvement in this group. CONCLUSION: The results of this retrospective study suggest that neomacrolides may be useful as an add-on therapy in patients with severe asthma and/or bronchiectasis. Older age may predict good response in patients with severe asthma, whereas older age, male gender and a higher HRCT score for bronchiectasis may predict therapeutic response in patients with bronchiectasis only. Prospective controlled trials of neomacrolides in patients with severe asthma are needed to confirm these observations.