Effects of ticagrelor and prasugrel on coronary microcirculation in elective percutaneous coronary intervention.

OBJECTIVE: To compare the effects of ticagrelor and prasugrel on absolute coronary blood flow (Q) and microvascular resistance (R) in patients with stable coronary artery disease (CAD) treated with elective percutaneous coronary intervention (PCI) (NCT05643586). Besides being at least as effective as prasugrel in inhibiting platelet aggregation, ticagrelor has been shown to have additional properties potentially affecting coronary microcirculation. METHODS: We randomly assigned 50 patients to ticagrelor (180 mg) or prasugrel (60 mg) at least 12 hours before intervention. Continuous thermodilution was used to measure Q and R before and after PCI. Platelet reactivity was measured before PCI. Troponin I was measured before, 8 and 24 hours after PCI. RESULTS: At baseline, fractional flow reserve, Q and R were similar in two study groups. Patients in the ticagrelor group showed higher post-PCI Q (242±49 vs 205±53 mL/min, p=0.015) and lower R values (311 (263, 366) vs 362 (319, 382) mm Hg/L/min, p=0.032). Platelet reactivity showed a negative correlation with periprocedural variation of Q values (r=-0.582, p<0.001) and a positive correlation with periprocedural variation of R values (r=0.645, p<0.001). The periprocedural increase in high-sensitivity troponin I was significantly lower in the ticagrelor compared with the prasugrel group (5 (4, 9) ng/mL vs 14 (10, 24) ng/mL, p<0.001). CONCLUSIONS: In patients with stable CAD undergoing PCI, pretreatment with a loading dose of ticagrelor compared with prasugrel improves post-procedural coronary flow and microvascular function and seems to reduce the related myocardial injury.

Validation of Coronary Angiography-Derived Vessel Fractional Flow Reserve in Heart Transplant Patients with Suspected Graft Vasculopathy.

Cardiac transplant-related vasculopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, coronary angiography-derived vessel fractional flow reserve (vFFR) has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease. Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic coronary artery disease, data on the use of vFFR in heart transplant recipients suffering from cardiac transplant-related arteriopathy are lacking. The aim of the presented study was to validate coronary angiography-derived vessel fractional flow reserve to calculate fractional flow reserve in HTx patients with and without cardiac transplant-related vasculopathy. A prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography was conducted. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/s in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Overall, 18,059 FFR values were extracted from the FFR pullback curves from 23 HTx patients. The mean age was 59.3 ± 9.7 years, the mean time after transplantation was 5.24 years [IQR 1.20, 11.25]. A total of 39 vessels from 23 patients (24 LAD, 11 LCX, 4 RCA) were analyzed. Mean distal vFFR was 0.87 ± 0.14 whereas invasive distal FFR was 0.88 ± 0.17. An excellent correlation was found between invasive distal FFR and vFFR (r = 0.92; p < 0.001). The correlation of the pullback tracing was high, with a correlation coefficient between vFFR and invasive FFR pullback values of 0.72 (95% CI 0.71 to 0.73, p < 0.001). The mean difference between vFFR and invasive FFR pullback values was -0.01 with 0.06 of SD (limits of agreements -0.12 to 0.13). In HTx patients, coronary angiography-derived FFR correlates excellently with invasively measured wire-derived FFR. Therefore, angiography derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy.

Simplified Assessment of the Index of Microvascular Resistance.

BACKGROUND: To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR). METHODS: This is a prospective, single-center study of patients with chronic coronary syndromes presenting with nonobstructive coronary artery disease. IMR was obtained using both intravenous (IV) adenosine and intracoronary (IC) papaverine. Each IMR measurement was obtained in duplicate. The primary objective was the agreement between IMR acquired using adenosine and papaverine. Secondary objectives include reproducibility of IMR and time required for the IMR measurement. RESULTS: One hundred and sixteen IMR measurements were performed in 29 patients. The mean age was 68.8 ± 7.24 years, and 27.6% was diabetics. IMR values were similar between papaverine and adenosine (17.7 ± 7.26 and 20.1 ± 8.6, p=0.25; Passing-Bablok coefficient A 0.58, 95% CI -2.42 to 3.53; coefficient B 0.90, 95% CI -0.74 to 1.07). The reproducibility of IMR was excellent with both adenosine and papaverine (ICC 0.78, 95% CI 0.63 to 0.88 and ICC 0.93, 95% CI 0.87 to 0.97). The time needed for microvascular assessment was significantly shortened by the use of IC papaverine (3.23 (2.84, 3.78) mins vs. 5.48 (4.94, 7.09) mins, p < 0.0001). CONCLUSION: IMR can be reliably measured using IC papaverine with similar results compared to intravenous infusion of adenosine with increased reproducibility and reduced procedural time. This approach simplifies the invasive assessment of the coronary microcirculation in the catheterization laboratory.

The in- and out-of-hospital management of HF patients: results from a nationwide Belgian survey.

BACKGROUND: We conducted a nationwide survey to describe the in-and out-of-hospital flow (diagnosis, treatment and follow-up) of patients with heart failure with reduced ejection fraction (HFrEF). METHOD: A survey was developed with five dedicated HF cardiologists. The data are all self-reported by cardiologists. RESULTS: The response rate was 84%. Presence of a dedicated HF cardiologist or HF nurse was indicated by 49% and 46% of the hospitals respectively. Devices (p < .05), angiotensin receptor neprilysin inhibitors, and rehabilitation are considered more standard of care therapy by dedicated compared to non-dedicated HF cardiologists. Most cardiologists indicated that target dosages of HF drugs can be reached in 25‒75% of patients. Achieving >75% of the target dose seems easier for angiotensin converting enzyme inhibitor/angiotensin receptor blockers (ACEI/ARB) (22%) and mineralocorticoid receptor antagonists (25%), compared to ß-blockers (10%) and angiotensin receptor neprilysin inhibitors (7%). 62%, 49% and 4% of the cardiologists indicated to use subtypes of angiotensin converting enzyme inhibitors, angiotensin receptor blockers and ß-blockers respectively not validated in the HF population. In the acute setting, dedicated HF cardiologists (23%) are less influenced by blood parameters for decongestion compared to non-dedicated HF cardiologists (39%). They tend to change patients more to guideline-recommended drugs (60% vs 47%). Six minutes walk test and ergospirometry are significantly more used by dedicated compared to non-dedicated HF cardiologists for HF drug change (17% and 29% vs 2% and 4%). CONCLUSION: This survey showed that a minority of hospitals have HF care. Those that do, report a higher implementation of guideline-recommended diagnosis, treatment and follow-up of HF patients. Competent authorities could use this survey as a tool to improve HF care.

Left-Sided Implantation of a Defibrillator Lead in Persistent Left Superior Vena Cava.

Persistent left superior vena cava (PLSVC) is a congenital venous abnormality, characterized by an enlarged coronary sinus, in most cases without haemodynamic consequences. We report the case of a patient with systolic heart failure undergoing implantation of a defibrillator lead through a PLSVC which was diagnosed at the moment of implantation. LEARNING POINTS: Persistent left superior vena cava (PLSVC) can be incidentally diagnosed during a procedure such as a left-sided central venous line or pacemaker implantation, and can be confirmed by manual contrast injection during the procedure.An enlarged coronary sinus on echocardiography should raise suspicion of PLSVC which can be confirmed by administration of echo-contrast or agitated saline in the left arm.Although lead implantation through a PLSVC is technically feasible, difficulties in lead positioning may be encountered because of the acute angle between the origin of the coronary sinus and the tricuspid valve.

DISENGAGE Registry.

BACKGROUND: During fractional flow reserve (FFR) measurement, the simple presence of the guiding catheter (GC) within the coronary ostium might create artificial ostial stenosis, affecting the hyperemic flow. We aimed to investigate whether selective GC engagement of the coronary ostium might impede hyperemic flow, and therefore impact FFR measurements and related clinical decision-making. METHODS: In the DISENGAGE (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, FFR was prospectively measured twice (with GC engaged [FFReng] and disengaged [FFRdis]) in 202 intermediate stenoses of 173 patients. We assessed (1) whether ΔFFReng-FFRdis was significantly different from the intrinsic variability of repeated FFR measurements (test-retest repeatability); (2) whether the extent of ΔFFReng-FFRdis could be clinically significant and therefore able to impact clinical decision-making; and (3) whether ΔFFReng-FFRdis related to the stenosis location, that is, proximal and middle versus distal coronary segments. RESULTS: Overall, FFR significantly changed after GC disengagement: FFReng 0.84±0.08 versus FFRdis 0.80±0.09, P<0.001. Particularly, in 38 stenoses (19%) with FFR values in the 0.81 to 0.85 range, GC disengagement was associated with a shift from above to below the 0.80 clinical cutoff, resulting into a change of the treatment strategy from medical therapy to percutaneous coronary intervention. The impact of GC disengagement was significantly more pronounced with stenoses located in proximal and middle as compared with distal coronary segments (ΔFFReng-FFRdis, proximal and middle 0.04±0.03 versus distal segments 0.03±0.03; P=0.042). CONCLUSIONS: GC disengagement results in a shift of FFR values from above to below the clinical cutoff FFR value of 0.80 in 1 out of 5 measurements. This occurs mostly when the stenosis is located in proximal and middle coronary segments and the FFR value is close to the cutoff value.

Impact of different anticoagulation management strategies on outcomes in atrial fibrillation: Dutch and Belgian results from the GARFIELD-AF registry.

BACKGROUND: The uptake rate of non-vitamin K oral anticoagulants (NOAC) for the treatment of non-valvular atrial fibrillation (AF) was far lower in the Netherlands (NL) compared to Belgium (BE). Also, patients on VKA in NL were treated with a higher target international normalized ratio (INR) range of 2.5 to 3.5. OBJECTIVES: To explore the effect of these differences on thromboembolism (TE) and bleeding. METHODS: Data from the GARFIELD-AF registry was used. Patients with new-onset AF and ≥1 investigator-determined risk factor for stroke were included between 2010 and 2016. Event rates from 2 years of follow-up were used. RESULTS: In NL and BE, 1186 and 1705 patients were included, respectively. Female sex (42.3% vs 42.2%), mean age (70.7 vs 71.3 years), CHA2 DS2 -VASc (3.1 vs 3.1), and HAS-BLED score (1.4 vs 1.5) were comparable between NL and BE. At diagnosis in NL vs BE, 72.1% vs 14.6% received vitamin K antagonists (VKA) and 17.8% vs 65.5% NOACs, varying greatly across cohorts. Mean INR was 2.9 (±1.0) and 2.4 (±1.0) in NL and BE, respectively. Event rates per 100 patient-years in NL and BE, respectively, of all-cause mortality (3.38 vs 3.90; hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15), ischemic stroke/TE (0.82 vs 0.72; HR 1.14, 95% CI 0.62-2.11), and major bleeding (2.06 vs 1.54; HR 1.33, 95% CI 0.89-1.99) did not differ significantly. CONCLUSIONS: In GARFIELD-AF, despite similar characteristics, patients on anticoagulants were treated differently in NL and BE. Although the rate of major bleeding was 33% higher in NL, variations in bleeding, mortality, and TE rates were not statistically significant.

Fatal Ischaemic Stroke During COVID-19 and Acute Lung Injury.

Severe COVID-19 may predispose to both venous and arterial thrombosis. We describe a patient with acute ischaemic stroke while suffering from COVID-19 and respiratory failure, necessitating mechanical ventilation. Deep sedation may delay diagnosis. LEARNING POINTS: A thrombotic stroke can complicate severe COVID-19.Prolonged deep sedation during mechanical ventilation of COVID-19 patients may delay the diagnosis of stroke.The hypercoagulability and a thrombo-inflammatory response in COVID-19 is characterized by an increase in D-dimers and fibrinogen.

Procedural microvascular activation in long lesions treated with bioresorbable vascular scaffolds or everolimus-eluting stents: the PROACTIVE trial.

AIMS: Significant platelet activation after long stented coronary segments has been associated with periprocedural microvascular impairment and myonecrosis. In long lesions treated either with an everolimus-eluting bioresorbable vascular scaffold (BVS) or an everolimus-eluting stent (EES), we aimed to investigate (a) procedure-related microvascular impairment, and (b) the relationship of platelet activation with microvascular function and related myonecrosis. METHODS AND RESULTS: Patients (n=66) undergoing elective percutaneous coronary intervention (PCI) in long lesions were randomised 1:1 to either BVS or EES. The primary endpoint was the difference between groups in changes of pressure-derived corrected index of microvascular resistance (cIMR) after PCI. Periprocedural myonecrosis was assessed by high-sensitivity cardiac troponin T (hs-cTnT), platelet reactivity by high-sensitivity adenosine diphosphate (hs-ADP)-induced platelet reactivity with the Multiplate Analyzer. Post-dilatation was more frequent in the BVS group, with consequent longer procedure time. A significant difference was observed between the two groups in the primary endpoint of ΔcIMR (p=0.04). hs-ADP was not different between the groups at different time points. hs-cTnT significantly increased after PCI, without difference between the groups. CONCLUSIONS: In long lesions, BVS implantation is associated with significant acute reduction in IMR as compared with EES, with no significant interaction with platelet reactivity or periprocedural myonecrosis.

Sacubitril/valsartan in heart failure and end-stage renal insufficiency.

The aim of this report is to describe the feasibility and tolerability of medical treatment with sacubitril/valsartan in a patient treated with hemodialysis. We describe the case of a 67-year-old man with heart failure with reduced ejection fraction due to an ischemic cardiomyopathy and renal insufficiency undergoing hemodialysis. Because of worsening heart failure with no other therapeutic options, a treatment with sacubitril/valsartan was started. Although this patient had a very low systolic blood pressure, he could tolerate a moderate dose of 49/51 mg twice daily. After initiation of sacubitril/valsartan, there was a symptomatic improvement with a clear reduction NT-proBNP, accompanied by a decrease in filling pressures. In conclusion, in this patient with severe heart failure undergoing hemodialysis, treatment with sacubitril/valsartan was feasible, safe, and improved heart failure symptoms.

Serial strain imaging in takotsubo syndrome with concomitant coronary artery disease.

We report a case of takotsubo syndrome (TTS) triggered by herpes encefalitis in the presence of significant triple vessel coronary artery disease (CAD). The typical ECG abnormalities, moderately elevated cardiac enzymes with disproportionally elevated brain natriuretic peptide (BNP) as well as the typical wall motion abnormalities on echocardiography and left ventricular (LV) angiography, were consistent with the diagnosis of TTS with concomitant CAD rather than an acute coronary syndrome. The normalization of the wall motion abnormalities, ejection fraction and longitudinal strain on serial echocardiography all support the diagnosis of takotsubo syndrome, especially in challenging cases.

Treatment patterns in anticoagulant therapy in patients with newly diagnosed atrial fibrillation in Belgium: results from the GARFIELD-AF registry.

Background: AF, anticoagulation, NOACs, changing patterns of prescription. Methods: We describe baseline data and treatment patterns of patients recruited in Belgium in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Recruitment began when novel oral anticoagulants (NOACs) were introduced and provides a unique picture of changing treatment patterns over time. 1713 patients with a new (≤6 weeks duration) diagnosis of non-valvular atrial fibrillation (NVAF) and at least one investigator-defined stroke risk factor were recruited between May 2012 and August 2016, and will be prospectively followed for at least 2 years. Results: Overall, anticoagulant use in Belgium was higher than in the rest of Europe: 80.1% of patients received an anticoagulant ± antiplatelet (AP) therapy (14.5% on vitamin K antagonists; 65.6% on NOAC), 10.7% AP therapy and 9.3% no antithrombotic therapy. Over time, we observed an increase in anticoagulant use and a decrease in AP use for stroke prevention. NOAC use in Belgium was the highest of Europe at the study start, with many countries catching up later. In high stroke risk patients (CHA2DS2-VASc ≥2), anticoagulants were used in 84.3%, leaving 15.7% unprotected. In low risk patients (CHA2DS2-VASc 0-1) anticoagulants were overused (58.7%). Factor Xa inhibitors were used more frequently than direct thrombin inhibitors. Conclusion: Guideline adherence on stroke prevention was higher in Belgium than in the rest of Europe, and increased over time. NOAC use in Belgium was the highest of Europe at the study start, with many countries catching up later. Possible reasons are discussed. Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT01090362.

Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.

AIMS: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. METHODS AND RESULTS: This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. CONCLUSION: The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Effective radiation dose, time, and contrast medium to measure fractional flow reserve.

OBJECTIVES: This study sought to define the additional effective radiation dose, procedural time, and contrast medium needed to obtain fractional flow reserve (FFR) measurements after a diagnostic coronary angiogram. BACKGROUND: The FFR measurements performed at the end of a diagnostic angiogram allow the obtaining of functional information that complements the anatomic findings. METHODS: In 200 patients (mean age 66 +/- 10 years) undergoing diagnostic coronary angiography, FFR was measured in at least 1 intermediate coronary artery stenosis. Hyperemia was achieved by intracoronary (n = 180) or intravenous (n = 20) adenosine. The radiation dose (mSv), procedural time (min), and contrast medium (ml) needed for diagnostic angiography and FFR were recorded. RESULTS: A total of 296 stenoses (1.5 +/- 0.7 stenoses per patient) were assessed. The additional mean radiation dose, procedural time, and contrast medium needed to obtain FFR expressed as a percentage of the entire procedure were 30 +/- 16% (median 4 mSv, range 2.4 to 6.7 mSv), 26 +/- 13% (median 9 min, range 7 to 13 min), and 31 +/- 16% (median 50 ml, range 30 to 90 ml), respectively. The radiation dose and contrast medium during FFR were similar after intravenous and intracoronary adenosine, though the procedural time was slightly longer with intravenous adenosine (median 11 min, range 10 to 17 min, p = 0.04) than with intracoronary adenosine (median 9 min, range 7 to 13 min). When FFR was measured in 3 or more lesions, radiation dose, procedural time, and contrast medium increased. CONCLUSIONS: The additional radiation dose, procedural time, and contrast medium to obtain FFR measurement are low as compared to other cardiovascular imaging modalities. Therefore, the combination of diagnostic angiography and FFR measurements is warranted to provide simultaneously anatomic and functional information in patients with coronary artery disease.

A rapid evolution from effusive-constrictive to constrictive pericarditis.

We present a case of a 69-year-old woman with constrictive pericarditis preceded by effusive-constrictive pericarditis. Echocardiography on admission revealed a mild pericardial effusion, pericardial thickening and a constrictive physiology in the absence of RV pressure/volume overload suggesting effusive-constrictive pericarditis. Echocardiographic follow-up showed gradual disappearance of the effusion within one month and an important thickening of the visceral and parietal pericardium up to 9 mm. Respiratory variation of the mitral and tricuspid inflow, prominent diastolic septum shift and high mitral annular TDI-velocities were indicative of constrictive pericarditis. Subsequent left/right heart catheterisation 3 months after the initial diagnosis confirmed constrictive pericarditis with elevated diastolic pressures equalized in the four heart chambers, square root sign, respiratory discordant change of the left and right systolic pressures and an inspiratory increase of the right atrial pressure. The patient remained symptomatic under treatment with aspirin and diuretics. A parietal and visceral pericardectomy was successfully performed with a favourable clinical evolution.

Transthoracic tissue Doppler imaging of the atria: a novel method to determine the atrial fibrillation cycle length.

BACKGROUND: The atrial fibrillation cycle length (AFCL) is a critical parameter for the perpetuation and termination of AF. In the present study, we evaluated a new method to measure the AFCL based on transthoracic tissue Doppler imaging (TDI) of the right atrium (RA) and left atrium (LA). METHODS: Twenty patients with AF (6 acute AF, 14 persistent or permanent AF) were studied. A quadripolar catheter was positioned at RA or LA to measure AFCL (AFCL(EGM), gold standard). Transthoracic echocardiography (apical 4-chamber view) was used to perform pulsed wave TDI at the free wall of RA or LA. AFCL(TDI) was defined as the time interval between two consecutive positive to negative crossings of the baseline of the atrial time velocity curves. AFCL(EGM) and AFCL(TDI) were measured at baseline and during a 10-minute infusion of flecainide (1.5 mg/kg). RESULTS: Measurement of AFCL(TDI) was feasible in all but one patient. At baseline, AFCL(EGM) was 170 +/- 22 ms, AFCL(TDI) 172 +/- 22 ms (difference 2 +/- 5 ms). AFCL(TDI) correlated significantly with AFCL(EGM) (R = 0.91, P < 0.0001). Bland-Altman analysis showed a bias of -2 ms with a 95% limit of agreement between -26 ms and +22 ms. During flecainide, the AFCL(TDI) method yielded an AFCL prolongation from 176 +/- 23 ms at baseline to 279 +/- 68 ms (P < 0.01) after 10 minutes of infusion (57 +/- 26%). CONCLUSIONS: (1) Tissue Doppler imaging of the atria during transthoracic echocardiography can be used to reliably determine the AFCL during both acute and persistent or permanent AF. (2) Continuous measurement of AFCL with TDI can be used to monitor the effect of antiarrhythmic drugs on atrial rate during AF. (3) This novel method is attractive because of the ease of acquiring the data and its noninvasive character.