Impact of coronary hyperemia on collateral flow correction of coronary microvascular resistance indices.

Recently, a novel method to estimate wedge pressure (Pw)-corrected minimal microvascular resistance (MR) was introduced. However, this method has not been validated since, and there are some theoretical concerns regarding the impact of different physiological conditions on the derivation of Pw measurements. This study sought to validate the recently introduced method to estimate Pw-corrected MR in a Doppler-derived study population and to evaluate the impact of different physiological conditions on the Pw measurements and the derivation of Pw-corrected MR. The method to derive "estimated" hyperemic microvascular resistance (HMR) without the need for Pw measurements was validated by estimating the coronary fractional flow reserve (FFRcor) from myocardial fractional flow reserve (FFRmyo) in a Doppler-derived study population (N = 53). From these patients, 24 had hyperemic Pw measurements available for the evaluation of hyperemic conditions on the derivation of Pw and its effect on the derivation of both "true" (with measured Pw) and "estimated" Pw-corrected HMR. Nonhyperemic Pw differed significantly from Pw measured in hyperemic conditions (26 ± 14 vs. 35 ± 14 mmHg, respectively, P < 0.005). Nevertheless, there was a strong linear relationship between FFRcor and FFRmyo in nonhyperemic conditions (R2 = 0.91, P < 0.005), as well as in hyperemic conditions (R2 = 0.87, P < 0.005). There was a strong linear relationship between "true" HMR and "estimated" HMR using either nonhyperemic (R2 = 0.86, P < 0.005) or hyperemic conditions (R2 = 0.85, P < 0.005) for correction. In contrast to a modest agreement between nonhyperemic Pw-corrected HMR and apparent HMR (R2 = 0.67, P < 0.005), hyperemic Pw-corrected HMR showed a strong agreement with apparent HMR (R2 = 0.88, P < 0.005). We validated the calculation method for Pw-corrected MR in a Doppler velocity-derived population. In addition, we found a significant impact of hyperemic conditions on the measurement of Pw and the derivation of Pw-corrected HMR.NEW & NOTEWORTHY The following are what is known: 1) wedge-pressure correction is often considered for the derivation of indices of minimal microvascular resistance, and 2) the Yong method for calculating wedge pressure-corrected index of microvascular resistance (IMR) without balloon inflation has never been validated in a Doppler-derived population and has not been tested under different physiological conditions. This study 1) adds validation for the Yong method for calculated wedge-pressure correction in a Doppler-derived study population and 2) shows significant influence of the physiological conditions on the derivation of coronary wedge pressure.

Relationship between peripheral and intracoronary blood flow in patients with angina and nonobstructive coronary arteries.

Coronary vasomotor dysfunction, an important underlying cause of angina and nonobstructive coronary arteries (ANOCA), encompassing coronary vasospasm, coronary endothelial dysfunction, and/or coronary microvascular dysfunction, is clinically assessed by invasive coronary function testing (ICFT). As ICFT imposes a high burden on patients and carries risks, developing noninvasive alternatives is important. We evaluated whether coronary vasomotor dysfunction is a component of systemic microvascular endothelial and smooth muscle dysfunction and can be detected using laser speckle contrast analysis (LASCA). Forty-three consecutive patients with ANOCA underwent ICFT, with intracoronary acetylcholine, adenosine, and flow measurements, to assess coronary vasomotor dysfunction. Cutaneous microvascular function was assessed using LASCA in the forearm, combined with vasodilators acetylcholine, sodium nitroprusside, and insulin and using EndoPAT, by measuring the reactive hyperemia index (RHI). Of the 43 included patients with ANOCA (79% women, 59 ± 9 yr old), 38 patients had coronary vasomotor dysfunction, including 28 with coronary vasospasm, 26 with coronary endothelial dysfunction, and 18 with coronary microvascular dysfunction, with overlapping endotypes. Patients with and without coronary vasomotor dysfunction had similar peripheral flow responses to acetylcholine, insulin, and RHI. In contrast, coronary vasomotor dysfunction was associated with lower peripheral flow responses to sodium nitroprusside (P < 0.001). An absolute flow response to sodium nitroprusside of 83.95 APU resulted in 86.1% sensitivity and 80.0% specificity for coronary vasomotor dysfunction (area under the ROC curve, 0.883; P = 0.006). In conclusion, this study provides evidence of systemic vascular smooth muscle dysfunction in patients with ANOCA with coronary vasomotor dysfunction and the diagnostic value of peripheral microvascular function testing as a noninvasive tool for detecting coronary vasomotor dysfunction.NEW & NOTEWORTHY This study provides proof of concept that assessment of the peripheral vasculature, particularly vascular smooth muscle cells measured using the LASCA technology holds potential as a noninvasive tool for detecting coronary vasomotor dysfunction. This finding highlights the potential of the LASCA technology in, for example, medication studies for coronary vasomotor dysfunction, especially when investigating whether medication improves vascular function, as repeated peripheral measurements are less invasive than invasive coronary function testing, the current gold standard.

Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry.

AIMS: The microvascular resistance reserve (MRR) was introduced as a means to characterize the vasodilator reserve capacity of the coronary microcirculation while accounting for the influence of concomitant epicardial disease and the impact of administration of potent vasodilators on aortic pressure. This study aimed to evaluate the diagnostic and prognostic performance of MRR. METHODS AND RESULTS: A total of 1481 patients with stable symptoms and a clinical indication for coronary angiography were included from the global ILIAS Registry. MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressure. The median MRR was 2.97 [Q1-Q3: 2.32-3.86] and the overall relationship between MRR and CFR was good [correlation coefficient (Rs) = 0.88, P < 0.005]. The difference between CFR and MRR increased with decreasing FFR [coefficient of determination (R2) = 0.34; Coef.-2.88, 95% confidence interval (CI): -3.05--2.73; P < 0.005]. MRR was independently associated with major adverse cardiac events (MACE) at 5-year follow-up [hazard ratio (HR) 0.78; 95% CI 0.63-0.95; P = 0.024] and with target vessel failure (TVF) at 5-year follow-up (HR 0.83; 95% CI 0.76-0.97; P = 0.047). The optimal cut-off value of MRR was 3.0. Based on this cut-off value, only abnormal MRR was significantly associated with MACE and TVF at 5-year follow-up in vessels with functionally significant epicardial disease (FFR <0.75). CONCLUSION: MRR seems a robust indicator of the microvascular vasodilator reserve capacity. Moreover, in line with its theoretical background, this study suggests a diagnostic advantage of MRR over other indices of vasodilatory capacity in patients with hemodynamically significant epicardial coronary artery disease.

Assessment of renal sympathetic control using invasive pressure and flow velocity measurements in humans.

Renal sympathetic innervation is important in the control of renal and systemic hemodynamics and is a target for pharmacological and catheter-based therapies. The effect of a physiological sympathetic stimulus using static handgrip exercise on renal hemodynamics and intraglomerular pressure in humans is unknown. We recorded renal arterial pressure and flow velocity in patients with a clinical indication for coronary or peripheral angiography using a sensor-equipped guidewire during baseline, handgrip, rest, and hyperemia following intrarenal dopamine (30 µg/kg). Changes in perfusion pressure were expressed as the change in mean arterial pressure, and changes in flow were expressed as a percentage with respect to baseline. Intraglomerular pressure was estimated using a Windkessel model. A total of 18 patients (61% male and 39% female) with a median age of 57 yr (range: 27-85 yr) with successful measurements were included. During static handgrip, renal arterial pressure increased by 15.2 mmHg (range: 4.2-53.0 mmHg), whereas flow decreased by 11.2%, but with a large variation between individuals (range: -13.4 to 49.8). Intraglomerular pressure increased by 4.2 mmHg (range: -3.9 to 22.1 mmHg). Flow velocity under resting conditions remained stable, with a median of 100.6% (range: 82.3%-114.6%) compared with baseline. During hyperemia, maximal flow was 180% (range: 111%-281%), whereas intraglomerular pressure decreased by 9.6 mmHg (interquartile range: 4.8 to 13.9 mmHg). Changes in renal pressure and flow during handgrip exercise were significantly correlated (ρ = -0.68, P = 0.002). Measurement of renal arterial pressure and flow velocity during handgrip exercise allows the identification of patients with higher and lower sympathetic control of renal perfusion. This suggests that hemodynamic measurements may be useful to assess the response to therapeutic interventions aimed at altering renal sympathetic control.NEW & NOTEWORTHY Renal sympathetic innervation is important in the homeostasis of systemic and renal hemodynamics. We showed that renal arterial pressure significantly increased and that flow decreased during static handgrip exercise using direct renal arterial pressure and flow measurements in humans, but with a large difference between individuals. These findings may be useful for future studies aimed to assess the effect of interventions that influence renal sympathetic control.

Dobutamine stress echocardiography during transcatheter edge-to-edge mitral valve repair predicts residual mitral regurgitation.

OBJECTIVES: The current study sought to determine whether low-dose dobutamine stress echocardiography (DSE) during transcatheter edge-to-edge mitral valve repair (TMVR) can predict residual mitral regurgitation (MR) at discharge. BACKGROUND: In most patients, TMVR can successfully reduce MR from severe to mild or moderate. However, general anesthesia during the intervention affects hemodynamics and MR assessment. At discharge transthoracic echocardiogram residual MR (>moderate) is present in 10%-30% of patients which is associated with worse clinical outcome. METHODS: In consecutive patients the severity of MR was determined at baseline, immediately after TMVR clip implantation and subsequently during low-dose DSE (both under general anesthesia) and at discharge. RESULTS: A total of 39 patients were included (mean age 76.1 ± 8.1 years, 39% male, 56% functional MR, 41% left ventricular ejection fraction < 45%). An increase of MR during DSE was seen in 11 patients, of whom 6 (55%) showed >moderate MR at discharge. None of the 28 patients without an increase of MR during DSE showed >moderate MR at discharge. The diagnostic performance of the test could be established at a sensitivity of 100% and a specificity of 85% in unselected patients. CONCLUSIONS: DSE during TMVR is a useful tool to predict residual MR at discharge. It could support procedural decision making, including implantation of additional clips and thus potentially improve clinical outcome.

Respiration-related variations in Pd/Pa ratio and fractional flow reserve in resting conditions and during intravenous adenosine administration.

AIMS: We evaluated the occurrence and physiology of respiration-related beat-to-beat variations in resting Pd/Pa and FFR during intravenous adenosine administration, and its impact on clinical decision-making. METHODS AND RESULTS: Coronary pressure tracings in rest and at plateau hyperemia were analyzed in a total of 39 stenosis from 37 patients, and respiratory rate was calculated with ECG-derived respiration (EDR) in 26 stenoses from 26 patients. Beat-to-beat variations in FFR occurred in a cyclical fashion and were strongly correlated with respiratory rate (R2  = 0.757, p < 0.001). There was no correlation between respiratory rate and variations in resting Pd/Pa. When single-beat averages were used to calculate FFR, mean ΔFFR was 0.04 ± 0.02. With averaging of FFR over three or five cardiac cycles, mean ΔFFR decreased to 0.02 ± 0.02, and 0.01 ± 0.01, respectively. Using a FFR ≤ 0.80 threshold, stenosis classification changed in 20.5% (8/39), 12.8% (5/39) and 5.1% (2/39) for single-beat, three-beat and five-beat averaged FFR. The impact of respiration was more pronounced in patients with pulmonary disease (ΔFFR 0.05 ± 0.02 vs 0.03 ± 0.02, p = 0.021). CONCLUSION: Beat-to-beat variations in FFR during plateau hyperemia related to respiration are common, of clinically relevant magnitude, and frequently lead FFR to cross treatment thresholds. A five-beat averaged FFR, overcomes clinically relevant impact of FFR variation.

Final five-year results of the REMEDEE Registry: Real-world experience with the dual-therapy COMBO stent.

OBJECTIVES: This final report from the REMEDEE Registry assessed the long-term safety and efficacy of the dual-therapy COMBO stent in a large unselected patient population. BACKGROUND: The bio-engineered COMBO stent (OrbusNeich Medical BV, The Netherlands) is a dual-therapy pro-healing stent. Data of long-term safety and efficacy of the this stent is lacking. METHODS: The prospective, multicenter, investigator-initiated REMEDEE Registry evaluated clinical outcomes after COMBO stent implantation in daily clinical practice. One thousand patients were enrolled between June 2013 and March 2014. RESULTS: Five-year follow-up data were obtained in 97.2% of patients. At 5-years, target lesion failure (TLF) (composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) was present in 145 patients (14.8%). Definite or probable stent thrombosis (ST) occurred in 0.9%, with no additional case beyond 3-years of follow-up. In males, 5-year TLF-rate was 15.6 versus 12.6% in females (p = .22). Patients without diabetes mellitus (DM) had TLF-rate of 11.4%, noninsulin-treated DM 22.7% (p = .001) and insulin-treated DM 41.2% (p < .001). Patients presenting with non-ST segment elevation acute coronary syndrome (NSTE-ACS) had higher incidence of TLF compared to non-ACS (20.4 vs. 13.3%; p = .008), while incidence with STE-ACS was comparable to non-ACS (10.7 vs. 13.3%; p = .43). CONCLUSION: Percutaneous coronary intervention with the dual-therapy COMBO stent in unselected patient population shows low rates of TLF and ST to 5 years. Remarkably, no case of ST was noted beyond 3 years.

Clinical outcomes at 2 years of the Absorb bioresorbable vascular scaffold versus the Xience drug-eluting metallic stent in patients presenting with acute coronary syndrome versus stable coronary disease-AIDA trial substudy.

BACKGROUND: Patients with acute coronary syndrome (ACS) might represent a specific subgroup, in which bioresorbable scaffold implantation in percutaneous coronary intervention (PCI), might lead to better outcomes when compared to conventional treatment with metallic drug eluting stents. In this prespecified subgroup analysis of the Amsterdam Investigator-Initiated Absorb Strategy All-Comers (AIDA) trial, we evaluated the clinical outcomes of Absorb bioresorbable vascular scaffold (BVS) versus Xience everolimus eluting stent (EES) treated patients presenting either with or without ACS. METHODS AND RESULTS: We classified AIDA patients on the basis of clinical presentation of ACS or of no-ACS. The rate of the 2-year primary endpoint of target vessel failure (TVF) was similar after treatment with Absorb BVS or Xience EES in ACS patients (10.2% versus 9.0% respectively; P = 0.49) and in no-ACS patients (11.7% versus 10.7%, respectively; P = 0.67) Definite or probable device thrombosis occurred more frequently with Absorb BVS compared to Xience EES in ACS patients (4.3% versus 1.7%, respectively, P = 0.03) as well as in no-ACS patients (2.4% versus 0.2%, respectively; P = 0.002). There were no statistically significant interactions between clinical presentation and randomized device modality for TVF (P = 0.80) and for the endpoint of definite or probable device thrombosis (P = 0.17). CONCLUSION: In the AIDA trial, the 2-year outcomes of PCI with Absorb BVS versus Xience EES were consistent in ACS and no-ACS patients: similar rates for TVF and consistently higher rates of definite or probable stent thrombosis under Absorb BVS versus Xience EES. There were no statistically significant interactions between clinical presentation and randomized device modality.

Three-year clinical outcomes after dual-therapy COMBO stent placement: Insights from the REMEDEE registry.

BACKGROUND: The bio-engineered COMBO stent (OrbusNeich Medical BV, The Netherlands) is a dual-therapy pro-healing stent. This novel technology may allow a shorter duration of dual antiplatelet therapy (DAPT) after stenting. We present the first 3 year clinical outcomes of patients treated with COMBO stent. METHODS AND RESULTS: The prospective, multicenter, investigator-initiated, all-comers REMEDEE Registry evaluates clinical outcomes after COMBO stent treatment. A 1,000 patients were enrolled between June 2013 and March 2014. Patients had a mean of 65 years ±11, 26% of the patients were females and 18% diabetics. More than 50% of patients presented with acute coronary syndrome, 60% of treated lesions were AHA/ACC lesion type B2 or C. Target lesion failure (TLF) at 3 year follow-up occurred in 10.7% of patients (N = 105). The separate components cardiac death, target vessel myocardial infarction and target lesion revascularization occurred in 4.1%, 2.0%, and 7.1%, respectively of patients. Definite stent thrombosis (ST) was observed in 0.7% of all patients. At 3-year follow-up there were only 73 patients taking DAPT. CONCLUSIONS: At 3-year follow-up, patients treated with COMBO stent in the present large prospective all-comers cohort, continue to show good clinical outcomes. Clinicaltrials.gov identifier: NCT01874002. CONDENSED ABSTRACT: The COMBO stent is a sirolimus-eluting stent with a luminal anti-CD34-antibody layer, that binds endothelial progenitor cells. These cells can differentiate to endothelial cells and stimulate early endothelialization of the stent. The REMEDEE Registry is the first large, multicenter, prospective, cohort study evaluating the clinical outcomes of 1,000 all-comers patients treated with COMBO stent. Target lesion failure at 3 year follow-up was 10.7% and the rate of definite ST was 0.7%.

Evaluation of clinical outcomes after COMBO stent treatment in patients presenting with acute coronary syndrome.

BACKGROUND: Patients presenting with acute coronary syndrome (ACS) are at increased risk of complications after percutaneous coronary intervention with stent placement compared to patients with stable angina (SA) treated in an elective setting. The novel pro-healing COMBO stent is a bio-engineered drug eluting stent designed to promote vessel healing. Therefore, the stent may reduce this difference in clinical outcomes between elective and ACS-patients and prevent late stent thrombosis. METHODS AND RESULTS: The European, prospective, multicenter, 1000 all-comers patient REMEDEE registry evaluates clinical outcomes after COMBO stent placement in ACS- and elective patients. The primary endpoint at 12 months is target lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target lesion revascularization. A total of 49.9% (n = 498) of patients presented with acute coronary syndrome. TLF was 7.1% in ACS patients, definite and probable stent thrombosis was observed in 0.5% of ACS patients and in all within 9 days post stenting. We found no significant difference in TLF between ACS and non-ACS patients and a low overall rate of TLF. CONCLUSIONS: The COMBO stent is a safe and efficient device for patients presenting with ACS. Low ST rate and only early stent thrombosis were observed. © 2017 Wiley Periodicals, Inc.

Recurrent angina and cardiac ischaemia as a presentation of pheochromocytoma: a case report.

Background: We present a case of a pregnant patient with recurrent angina, in which her symptoms were initially attributed to coronary artery spasm. However, during follow-up, she was diagnosed as having pheochromocytoma, a rare neuroendocrine tumour. Case summary: The 35-year-old patient was admitted to the hospital because of chest pain and elevated cardiac troponins after the use of MDMA. Physical examination, electrocardiogram, echocardiography, coronary angiogram, and cardiac MRI were normal. Symptoms were attributed to coronary spasm, and a calcium antagonist was started. Ten months later, when 36 weeks pregnant, her symptoms returned. One week later, the patient was readmitted to the hospital with signs of acute left ventricular (LV) failure, highly elevated troponins, and severe global LV dysfunction. Urgent section caesarean was performed due to maternal morbidity and foetal tachycardia. During section, flushes and marked variability in blood pressure were noted. Laboratory metanephrines testing was performed. LV function recovered within 3 days without any therapeutic intervention. However, chest pain reoccurred, now accompanied with headaches, malignant hypertension, and accelerated idiopathic ventricular rhythms. (Nor)metanephrines tests were positive. A solid lesion in the right adrenal on CT scan confirmed the diagnosis of pheochromocytoma. Fluid repletion and alpha-blocker therapy were started. Due to persistent symptoms, urgent laparoscopic adrenalectomy was performed. Hereafter, the patient remained without symptoms. Discussion: A pheochromocytoma may present with recurrent angina and can result in a catecholamine-induced cardiomyopathy. It is important to timely recognize this diagnosis in order to minimize morbidity and mortality.

Percutaneous patent foramen ovale closure for hypoxaemia at the age of 73: a case report showing immediate benefit.

Background: Approximately 25% of the general population has a patent foramen ovale (PFO) that remains asymptomatic in the vast majority. Right-to-left shunt (RLS)-mediated hypoxaemia is a rare associated condition of PFO. Case summary: This report describes a case of percutaneous PFO closure for hypoxaemia in a 73-year-old patient showing immediate clinical benefit. She experienced progressive dyspnoea on exertion requiring oxygen therapy. SaO2 was 87% at rest without oxygen therapy, which increased to 98% after percutaneous PFO closure. Discussion: Most PFOs remain clinically insignificant but RLS-mediated hypoxaemia is a rare phenomenon that can occur even at advanced age. Percutaneous PFO closure is a safe and effective therapy option that provides immediate improvement of hypoxaemia.

Do electrocardiographic changes induced during intracoronary vasospasm provocation testing reflect those during spontaneous angina episodes in patients with vasospastic angina?: a case series.

Background: According to the Coronary Vasomotor Disorders International Study (COVADIS) group, the ECG criteria supporting the diagnosis of vasospastic angina (VSA) in spontaneous episodes or induced during intracoronary spasm testing are similar. However, it remains elusive whether acetylcholine-induced ECG changes during epicardial spasms reflect ECG changes that occur during the height of a spontaneous episode. Case summary: We present four patients diagnosed with VSA during intracoronary spasm testing, of whom the ECG characteristics during spasm testing and a spontaneous angina episode are described. All patients have >90% coronary epicardial vasoconstriction in one or more vessels during acetylcholine provocation. ECGs at the height of a spontaneous episode and during acetylcholine-induced coronary spasm are found to be different in three out of four patients. Discussion: In patients with VSA, the ECG at the height of a spontaneous episode and during acetylcholine-induced coronary artery spasm may differ substantially. In patients with symptoms suspicious of VSA, every effort should be undertaken to obtain ECGs during the height of a spontaneous episode of angina pectoris and there should be a low threshold to perform intracoronary function testing.

Myocardial Bridging as a Trigger in Angina With No Obstructive Coronary Artery Disease.

We present 2 patients with angina with no obstructive coronary artery disease and concomitant myocardial bridging. Despite maximal tolerated pharmacotherapy, symptoms remained. Invasive anatomical and hemodynamic assessment identified myocardial bridging as a contributing cause of angina. Following heart team discussion, both patients underwent successful coronary artery unroofing of the left anterior descending artery.

Higher Edmonton Frail Scale prior to transcatheter Aortic Valve Implantation is related to longer hospital stay and mortality.

BACKGROUND: International guidelines for the management of valvular heart disease recommend frailty assessment prior to Transcatheter Aortic Valve Implantation (TAVI), however there is no consensus how to assess frailty. We investigated whether frailty status assessed with the Edmonton Frail Scale (EFS, range 0-17 points) relates to length of stay (LOS), short- and long-term mortality and adverse outcomes after TAVI. METHODS: In this study we included 357 patients between April 2016 till December 2018. EFS was assessed at baseline. Patients were classified into low (0-3), intermediate (4-7) or high frailty status (8-17). LOS was defined as the number of days between admission and discharge. Mortality data were obtained up to four years after TAVI. Adverse events were defined by Valve Academic Research Consortium (VARC)-2 criteria and collected <30 days after TAVI. RESULTS: Patients with higher frailty status had longer median LOS (days (IQR): low 5 (3), intermediate 6 (4) and high 7 (5), p < 0.001) and higher mortality: low vs intermediate vs high at 30 days 0.5%, 2.2%, 7.0% (p = 0.050), 1 year 3.7%, 10.0%, 15.2% (p = 0.052), 2 years 9.2%, 17.8%, 31.7% (p = 0.003), 3 years 17.2%, 24.0, 47.0% (p = 0.001) and 4 years 19.6%, 30.8%, 55.6% (p < 0.001). Frail patients received more often a pacemaker (2.6%, 6.6%, 13.5%, p = 0.048). CONCLUSION: In clinical practice, the EFS is a useful tool to screen for frailty in TAVI patients. This tool may possibly be expanded to determine benefit versus harm-risk in these patients and whether specific pre-procedurally interventions are needed in order to reduce mortality.

Persistence of residual shunt at 6 and 12 months after transoesophageal echocardiography-guided percutaneous closure of a patent foramen ovale for cryptogenic stroke.

BACKGROUND: Young patients suffering from cryptogenic stroke alongside a patent foramen ovale (PFO) are often considered for percutaneous device closure to reduce the risk of stroke recurrence. Residual right-to-left shunt after device closure may persist in approximately a quarter of the patients at 6 months, and some may close at a later time point. This study aimed to assess the prevalence and persistence of residual right-to-left shunt after percutaneous PFO closure. METHODS: Consecutive patients undergoing transoesophageal echocardiography-guided PFO closure for cryptogenic stroke between 2006 and 2021, with echocardiographic follow-up including contrast bubble study and Valsalva manoeuvre, were enrolled. Follow-up transthoracic echocardiography was performed at 6 months and repeated at 12 months in case of residual right-to-left shunt. Primary outcomes included the prevalence and grade of residual right-to-left shunt at 6 and 12 months after percutaneous PFO closure. RESULTS: 227 patients were included with a mean age of 43±11 years and 50.2% were women. At 6-month follow-up, 72.7% had no residual right-to-left shunt, 12.3% small residual right-to-left shunt, 6.6% moderate residual right-to-left shunt and 8.4% large residual right-to-left shunt. At 12-month follow-up, the presence of residual right-to-left shunt in all patients was 12.3%, of whom 6.6% had small residual right-to-left shunt, 2.6% had moderate residual right-to-left shunt and 3.1% had large residual right-to-left shunt. CONCLUSIONS: Residual right-to-left shunts are common at 6 months after percutaneous closure of PFO. However, the majority are small and two-thirds of residual right-to-left shunts achieve complete closure between 6 and 12 months.

Assessment of coronary endothelial dysfunction using contemporary coronary function testing.

BACKGROUND: The established diagnosis of coronary endothelial dysfunction (CED) is through the response to low-dose acetylcholine during invasive coronary function testing (CFT). Current diagnostic criteria encompass deficient epicardial vasodilation and/or insufficient increase in coronary blood flow (CBF) calculated from additional Doppler flow velocity measurements. The aim is to evaluate the diagnostic yield of using angiographic epicardial vasomotion and CBF as single criteria for diagnosing CED during CFT. METHODS: A total of 110 patients with angina and non-obstructive coronary arteries who underwent clinically indicated CFT were included. CED was defined as any reduction in epicardial diameter through quantitative coronary angiography and/or < 50 % increase in CBF compared to baseline after low-dose acetylcholine. RESULTS: Based on current diagnostic criteria, 78 % of patients (N = 86/110) was diagnosed with CED. When only considering epicardial diameter, 24 % CED (N = 21/86) and 50 % severe CED diagnoses (N = 19/38) were missed. When only considering CBF, 27 % CED (N = 23/86) and 18 % severe CED diagnoses (N = 7/38) were missed. A similar diagnostic yield for CED detection was found for both parameters (OR: 0.913, 95 %CI 0.481-1.726, p = 0.763). The incidence of CFT diagnoses was comparable among all groups. CONCLUSIONS: As single parameters, both epicardial diameter and CBF were ineffective in accurately diagnosing CED compared to the current diagnostic criteria. Combining both parameters is necessary to diagnose the complete spectrum of CED, as missed diagnoses of deficient CBF responses (e.g., microvascular CED) and epicardial vasomotion (e.g., epicardial CED) might occur when relying on these parameters as single diagnostic criteria for CED.

Correction: van Veelen et al. First-in-Human Drug-Eluting Balloon Treatment of Vulnerable Lipid-Rich Plaques: Rationale and Design of the DEBuT-LRP Study. J. Clin. Med. 2023, 12, 5807.

In the original publication [...].

Comparison of the Diagnostic Yield of Intracoronary Acetylcholine Infusion and Acetylcholine Bolus Injection Protocols During Invasive Coronary Function Testing.

Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina with no obstructive coronary arteries in patients. Both can be diagnosed by invasive coronary function testing (ICFT) using acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared with a 1-minute ACh bolus injection protocol in testing CED and CAS. We evaluated 220 consecutive patients with angina and no obstructive coronary arteries who underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion, and thereafter 110 patients using 1-minute bolus injections, because of a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low-dose ACh and CAS according to the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%, p = 0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3 vs 1-minute protocol (24% vs 44%, p = 0.004). Including T-wave abnormalities in the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as a diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as a diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.