Impact of preceding acetylcholine provocation testing on following coronary physiological assessment during an interventional diagnostic procedure.

BACKGROUND: Intracoronary acetylcholine (ACh) provocation test and coronary physiological assessment are useful interventional diagnostic procedures for evaluating ischemia with no obstructive coronary arteries (INOCA). However, the appropriate sequential order of the diagnostic procedures has been a matter of debate. We investigated the impact of preceding ACh provocation on following coronary physiological assessment. METHODS: Patients suspected of INOCA underwent invasive coronary physiological assessment using thermodilution method and were divided into two groups according to the implementation of ACh provocation test. The ACh group was further divided into the positive and negative ACh groups. In the ACh group, intracoronary ACh provocation was performed before the invasive coronary physiological assessment. The main interest of this study was to compare coronary physiological indices among the no ACh, negative ACh, and positive ACh groups. RESULTS: Of 120 patients, the no ACh, and negative and positive ACh groups included 46 (38.3 %), 36 (30.0 %), and 38 (31.7 %), respectively. Fractional flow reserve was lower in the no ACh group than in the ACh group. Resting mean transit time was significantly longer in the positive ACh group, followed by the no ACh and negative ACh groups (1.22 ±â€¯0.55 vs. 1.00 ±â€¯0.46 vs. 0.74 ±â€¯0.36 s, p < 0.001). Index of microcirculatory resistance and coronary flow reserve did not differ significantly among the three groups. CONCLUSIONS: Preceding ACh provocation influenced following physiological assessment, particularly when ACh test was positive. Further studies are warranted to determine which interventional diagnostic procedure, ACh provocation or physiological assessment, should be preceded in the invasive evaluation of INOCA.

Characterization and implications of intracoronary hemodynamic assessment during coronary spasm provocation testing.

BACKGROUND: Current diagnostic criteria for coronary spasm are based on patient's symptoms, ECG shifts and epicardial vasoconstriction during acetylcholine (ACh) spasm testing. AIMS: To assess the feasibility and diagnostic value of coronary blood flow (CBF) and resistance (CR) assessment as objective parameters during ACh testing. METHODS: Eighty-nine patients who underwent intracoronary reactivity testing including ACh testing with synchronous Doppler wire-based measurements of CBF and CR were included. Coronary microvascular and epicardial spasm, respectively, were diagnosed based on COVADIS criteria. RESULTS: Patients were 63 ± 13 years old, predominantly female (69%) and had preserved LV ejection fraction (64 ± 8%). Overall, assessment of CBF and CR during ACh testing revealed a decrease in CBF of 0.62 (0.17-1.53)-fold and an increase of CR of 1.45 [0.67-4.02]-fold in spasm patients compared to 2.08 (1.73-4.76) for CBF and 0.45 (0.44-0.63) for CR in patients without coronary spasm (both p < 0.01). Receiver operating characteristic revealed a high diagnostic ability of CBF and CR (AUC 0.86, p < 0.001, respectively) in identifying patients with coronary spasm. However, in 21% of patients with epicardial spasm and 42% of patients with microvascular spasm a paradoxical response was observed. CONCLUSIONS: This study demonstrates feasibility and potential diagnostic value of intracoronary physiology assessments during ACh testing. We observed opposite responses of CBF and CR to ACh in patients with positive vs. negative spasm test. While a decrease in CBF and an increase in CR during ACh seem pathognomonic for spasm, some patients with coronary spasm demonstrate paradoxical ACh response demanding further scientific investigations.

Assessment of coronary spasms with transluminal attenuation gradient in coronary computed tomography angiography.

PURPOSE: To evaluate the imaging features of coronary spasm, including transluminal attenuation gradient (TAG) on coronary computed tomography angiography (CCTA), in patients with vasospastic angina (VA). METHODS: A total of 43 patients with a high clinical likelihood of VA were included in the study. All the subjects underwent double CCTA acquisition: CCTA without a vasodilator ('baseline CT') and CCTA during continuous intravenous nitrate infusion ('IV nitrate CT'). A catheterized ergonovine provocation test was used to determine true VA patients. Coronary spasm is classified into focal- and diffuse-types according to morphological differences. We measured TAG and contrast enhancement of the proximal ostium (ProxHU) of each coronary artery for both the baseline and IV nitrate CT. RESULTS: Twenty-four patients (55.8%) showed positive results of coronary vasospasm on the provocation test. Thirty-eight vessels showed coronary spasms (29.5%): Focal-type in nine vessels (24%), and diffuse-type in 29 (76%). In the baseline CT, LCX showed significantly lower (steeper) TAG in spasm(+) vessels than in spasm(-) vessels, while LAD and RCA showed no significant differences in TAG. The ProxHU of LAD showed significantly lower values in spasm(+) vessels than in spasm(-) vessels, while the other vessels did not show significant differences in ProxHU. For IV nitrate CT, there were no significant differences in either the TAG and ProxHU between spasm(+) and (-) vessels for all the three vessel types. In subgroup analysis for spasm(+) vessels, diffuse spasms showed significantly lower TAG than focal spasms, while the ProxHU did not differ between the two types of spasm. CONCLUSIONS: A relatively large percentage of coronary spasms present as diffuse type, and the TAG values significantly differed according to the morphological type of the coronary spasm.

Role of acetylcholine spasm provocation test as a pathophysiological assessment in nonobstructive coronary artery disease.

Coronary angiography (CAG) sometimes shows nonobstructive coronary arteries in patients with suspected angina or acute coronary syndrome (ACS). The high prevalence of nonobstructive coronary artery disease (CAD) in those patients has recently been reported not only in Japan but also in Western countries, and is clinically attracting attention. Coronary spasm is considered to be one of the leading causes of both suspected stable angina and ACS with nonobstructive coronary arteries. Coronary spasm could also be associated with left ventricular dysfunction leading to heart failure, which could be improved following the administration of calcium channel blockers. Because we rarely capture spontaneous attacks of coronary spasm with electrocardiograms or Holter recordings, an invasive diagnostic modality, acetylcholine (ACh) provocation test, can be useful in detecting coronary spasm during CAG. Furthermore, we can use the ACh-provocation test to identify high-risk patients with coronary spasm complicated with organic coronary stenosis, and then treat with intensive care. Nonobstructive CAD includes not only epicardial coronary spasm but also microvascular spasm or dysfunction that can be associated with recurrent anginal attacks and poor quality of life. ACh-provocation test could also be helpful for the assessment of microvascular spasm or dysfunction. We hope that cardiologists will increasingly perform ACh-provocation test to assess the pathophysiology of nonobstructive CAD.

A review of diagnosis, etiology, assessment, and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.

Myocardial infarction (MI) in the absence of obstructive coronary artery disease (MINOCA) is prevalent in around 5% of acute myocardial infarction (AMI) presentations. MINOCA is a heterogeneous entity with many different etiologies. It is important for health care providers to familiarize themselves with the disease process, presentation, and possible underlying causes in order to guide appropriate management strategies. In this article, the authors review the contemporary definition, etiologies and assessment, and management for AMI patients with MINOCA.

Assessment of coronary vasomotor responses to acetylcholine in German and Japanese patients with epicardial coronary spasm-more similarities than differences?

Coronary spasm is an established cause for angina pectoris. Ethnic differences have been suggested among Asian compared to Caucasian patients regarding prevalence, gender distribution, and angiographic patterns of coronary spasm. The aim of this study was to compare contemporary German and Japanese patients with coronary spasm. Between 2011 and 2015, 149 patients with resting angina and unobstructed coronary arteries with acetylcholine-induced epicardial spasm were enrolled in Stuttgart, Germany (n = 69) and Sendai, Japan (n = 80). All patients underwent intracoronary acetylcholine testing according to a standardized protocol. Comprehensive analysis included type of spasm (focal/diffuse), dose of acetylcholine leading to spasm, and frequency of multivessel spasm. Patients in this study were 61 ± 11 years old, predominantly female (54%), and had normal left ventricular ejection fraction (73 ± 9%). Diffuse spasm was the most prevalent type of spasm (85%) whereas focal spasm was found in the remaining 15% of patients. 31% of patients had multivessel spasm. Comparing the German with the Japanese patients, distribution of spasm type (focal/diffuse, p = 0.19) and frequency of multivessel spasm (p = 0.22) were comparable. Moreover, when Japanese patients were compared with German patients and diffuse spasm with focal spasm patients, respectively, no significant differences were observed regarding the acetylcholine dose required to induce spasm (p = 0.078 and p = 0.46, respectively). In conclusion, diffuse epicardial coronary spasm is the most frequent finding among German and Japanese patients with resting angina, unobstructed coronary arteries, and epicardial spasm on acetylcholine testing. Japanese and German patients share several similarities including comparable types of spasm and frequency of multivessel spasm.

[Assessment of adherence to antihypertensive drugs in patients with resistant hypertension receiving optimal treatment]. / Évaluation de l'adhérence aux médicaments antihypertenseurs chez des patients avec hypertension artérielle résistante recevant un traitement optimal.

OBJECTIVES: The primary objective was to estimate the proportion of non-adherence to antihypertensive drugs in patients with an apparently resistant hypertension despite optimal medical treatment. The secondary objective was to identify related factors to poor adherence. METHODS: Monocentric, prospective and observational study, including consecutive patients, managed for an apparently resistant hypertension between January 2014 and December 2017, with an ambulatory blood pressure measurement (ABP) in the past year and a thorough etiological work up in the 2 past years. Hypertension was considered resistant if the daytime ABP was ≥ 135/85mmHg and/or the 24hours ABP≥to 130/80mmHg, despite 4 antihypertensive medications at optimal doses. Adherence to treatment was assessed by the eight-item Morisky Scale (MMAS-8). RESULTS: We enrolled 386 patients, with a mean age of 64.6 years, and 48.2% of men. The mean office blood pressure, 24hours and daytime APB were 178.6/101.3mmHg, 164.4/97.2mmHg and 170.5/99.7mmHg respectively. The proportions of low, medium and high adherence were 24.5%, 47.6% and 27.9% respectively. Associated-factors with poor adherence were female sex, low education level, celibacy, polypharmacy and lack of home self-blood pressure monitoring. CONCLUSION: Over two out of three patients with an apparently resistant hypertension under optimal treatment were partially or fully nonadherent to treatment in our study. Assessment of adherence would be systematic in these patients before implementing complex investigations or non-pharmacologic invasive procedures.

Association of statin therapy with clinical outcomes in patients with vasospastic angina: Data from Korean health insurance review and assessment service.

There is conflicting evidence for the clinical benefit of statin therapy in patients with vasospastic angina (VSA). We investigated the association of statin therapy with clinical outcomes in relatively large populations with clinically suspected VSA from a nationwide population-based database. Data were collected from the Health Insurance Review and Assessment database records of 4,099 patients that were in an intensive care unit with VSA between January 1, 2008 and May 31, 2015. We divided the patients into a statin group (n = 1,795) and a non-statin group (n = 2,304). The primary outcome was a composite of cardiac arrest and acute myocardial infarction (AMI). The median follow-up duration was 3.8 years (interquartile range: 2.2 to 5.8 years). Cardiac arrest or AMI occurred in 120 patients (5.2%) in the statin group, and 97 patients (5.4%) in the non-statin group (P = 0.976). With inverse probability of treatment weighting, there was no significant difference in the rate of cardiac arrest or AMI between the two groups (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.76-1.30; P = 0.937), or even between the non-statin group and high-intensity statin group (adjusted HR, 1.08; 95% CI, 0.69-1.70; P = 0.75). The beneficial association of statin use with the primary outcome was consistently lacking across the various comorbidity types. Statin therapy was not associated with reduced cardiac arrest or AMI in patients with VSA, regardless of statin intensity. Prospective, randomized trials will be needed to confirm our findings.

Differential prognosis of vasospastic angina according to presentation with sudden cardiac arrest or not: Analysis of the Korean Health Insurance Review and Assessment Service.

BACKGROUND: The long-term prognosis of vasospastic angina (VSA) patients presenting with aborted sudden cardiac death (ASCD) is still unknown. We sought to compare the long-term clinical outcomes between VSA patients presenting with and without ASCD by retrospective analysis of a nationwide population-based database. METHODS: A total of 6972 patients in the Health Insurance Review and Assessment database who were hospitalized in the intensive care unit with VSA between July 1, 2007 and May 31, 2015 were enrolled. Primary outcome was the composite of cardiac arrest and acute myocardial infarction after discharge. RESULTS: Five hundred ninety-eight (8.6%) VSA patients presented with ASCD. On inverse probability of treatment weighting, ASCD patients had a significantly increased risk of the composite of cardiac arrest and acute myocardial infarction (adjusted hazard ratio, 2.52; 95% confidence interval, 1.72-3.67; p < 0.001) during the median follow-up duration of 4 years. The association of ASCD presentation with a worse outcome in terms of primary outcome was consistent across various subgroups, including comorbidity type and use of vasodilators (all p-values for interaction: non-significant). ASCD patients treated with an implantable cardioverter defibrillator (ICD) had a lower incidence of the composite of cardiac arrest and acute myocardial infarction during follow-up than those without an ICD (p = 0.009). CONCLUSIONS: VSA patients that present with ASCD are at increased risk of cardiac arrest or myocardial infarction during long-term follow-up despite adequate vasodilator therapy. An ICD is a potential therapeutic option for secondary prevention.

[Renal artery stenosis long time after renal denervation for resistant hypertension]. / Sténose de l'artère rénale à distance d'une dénervation rénale pour HTA résistante.

The onset of renal artery stenosis following a renal denervation is rare and occurs in the first few months after renal denervation. We report the onset of renal artery stenosis a long time after the renal denervation for resistant hypertension. This is a 74 year-old patient who stopped smoking in 1980 and who was treated for dyslipidemia with a revascularized coronary artery disease in 2011, a well-stabilized peripheral arterial disease since 2001, a stable asymptomatic carotid atheroma and a good kidney function. His hypertension known since 1995 became resistant. After the control of renal arteries by angio-CT scan, he had a renal denervation in October 2012. His blood pressure decreased 3 months later confirmed by self-blood pressure monitoring (SBPM) and ambulatory blood pressure monitoring (ABPM) with a CT scan with a non-significant renal artery stenosis in January 2014. He remained normotensive under treatment until July 2015 but his hypertension became uncontrolled at the end of 2015 then resistant and severe confirmed by SBPM in April 2017, despite a 5-drug antihypertensive treatment associated to atorvastatin and clopidogrel confirmed by SBPM in April 2017. A left post-ostial renal artery stenosis with decrease in size of left kidney and cortex as compared to 2011 was detected at CT and treated by angioplasty. It was associated with a rapid decrease in blood pressure but unfortunately a new increase related to a restenosis occurred at the end of 2017, which justified a new angioplasty. Discussion about the etiology and the management of this renal post-denervation late stenosis.

Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders.

Intracoronary acetylcholine provocation testing (ACH-test) is an established method for assessment of epicardial coronary artery spasm in the catheterization laboratory which was introduced more than 30 years ago. Due to the short half-life of acetylcholine it can only be applied directly into the coronary arteries. Several studies have demonstrated the safety and clinical usefulness of this test. However, acetylcholine testing is only rarely applied in the U.S. or Europe. Nevertheless, it has been shown that 62% of Caucasian patients with stable angina and unobstructed coronary arteries on coronary angiography suffer from coronary vasomotor disorders that can be diagnosed with acetylcholine testing. In recent years it has been appreciated that the ACH-test not only assesses the presence of epicardial spasm but that it can also be useful for the detection of coronary microvascular spam. In such cases no epicardial spasm is seen after injection of acetylcholine but ischemic ECG shifts are present together with a reproduction of the patient's symptoms during the test. This article describes the experience with the ACH-test and its implementation in daily clinical routine.

Renal Denervation in Patients with Resistant Hypertension-Assessment by 3T Renal 23Na-MRI: Preliminary Results.

BACKGROUND/AIM: Renal denervation (RDN) has been considered a promising therapy option for patients suffering from therapy-resistant hypertension. Besides, in blood-pressure regularization, the kidneys play a fundamental role in sodium ((23)Na) homeostasis. This study assesses the effect of RDN on renal (23)Na concentration using (23)Na magnetic resonance imaging (MRI). PATIENTS AND METHODS: Two patients with therapy-resistant hypertension underwent RDN. (23)Na-MRI, (1)H-MRI, including diffusion weighted imaging (DWI), as well as endothelial dysfunction assessment, were performed 1 day prior, as well as 1, 30 and 90 days after RDN. RESULTS: The renal corticomedullary (23)Na gradient did not change after RDN for all time points. Additionally, functional imaging and retinal vessel parameters were not influenced by RDN. Results regarding blood pressure changes and arterial stiffness, as well as patients' clinical outcome, were heterogeneous. CONCLUSION: RDN does not seem to alter renal (23)Na concentration gradients, as measured by MRI.

A new hope in the treatment of coronary vasospasm: bosentan.

Atherosclerosis is the most important cause of acute coronary syndromes. The mediators that trigger vasospasm, including endothelin and serotonin, are synthesized and secreted into circulation from atherosclerotic plaques and surrounding tissues. A 68-year-old man was hospitalized due to acute coronary syndrome four times in a one-year period. The patient presented to emergency service again with heartburn and a pressure-like pain in his upper abdomen in February 2012. He was admitted to the coronary care unit with the detection of a more than three-fold increase in troponin values and ischemic changes on electrocardiography. By decision of the cardiology council, the endothelin receptor antagonist, bosentan was added to the treatment. There were no contraindications to this medication according to his blood and hepatic indicators. After confirmation of the Social Security Institution, bosentan was started as 62.5 mg twice a day. After the first month, the dose was increased to 125 mg b.i.d. As of completion of the eighth month of treatment with bosentan, the patient had not been hospitalized due to angina attack or acute coronary syndrome.

Gender differences in the clinical characteristics and outcomes of patients with vasospastic angina--a report from the Japanese Coronary Spasm Association.

BACKGROUND: Accumulating evidence has demonstrated the gender differences in the clinical characteristics and outcomes of patients with ischemic heart disease. However, it remains to be elucidated whether it is also the case for vasospastic angina (VSA). METHODS AND RESULTS: We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median age 66 years) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. As compared with male patients, female patients were characterized by older age (median 69 vs. 66 years), lower incidence of smoking (20% vs. 72%) and less significant organic stenosis (9% vs. 16%) (all P=0.001). Multivariate analysis demonstrated that the predictors of major adverse cardiac events (MACE) were considerably different by genders; women were more associated with age and electrical abnormalities, whereas men with structural abnormalities. Overall 5-year MACE-free survival was comparable between both genders. However, when the patients were divided into 3 groups by age [young (<50 years), middle-aged (50-64 years) and elderly (≥65 years)], the survival was significantly lower in the young female group (young 82%, middle-aged 92%, elderly 96%, P<0.01), where a significant interaction was noted between age and smoking. In contrast, the survival was comparable among the 3 age groups of male patients. CONCLUSIONS: These results indicate that there are gender differences in the characteristics and outcomes of VSA patients, suggesting the importance of gender-specific management of the disorder.

In vivo assessment of ergonovine-induced coronary artery spasm by 64-slice multislice computed tomography.

BACKGROUND: The potential of multislice CT (MSCT) to predict coronary spasm has not been elucidated. The aim of this study was to investigate whether the morphological features observed on MSCT at the site of ergonovine-induced epicardial spasm could be used as diagnostic criteria for coronary spasm. METHODS AND RESULTS: A total of 296 plaques in 199 patients with clinically suspected coronary spastic angina without coronary stenosis (<75%) who underwent invasive angiography with intravenous ergonovine provocative testing were analyzed by MSCT. Calcification, CT attenuation, and patterns of vascular remodeling were evaluated in each plaque by MSCT. Plaques were divided into spasm group or nonspasm group based on the results of the ergonovine provocative test. On a per-plaque basis, noncalcified plaques were more frequently observed in the spasm group (96% versus 20%, P<0.01). Intermediate attenuation plaques (CT density ≥53.8 Hounsfield units identified by receiver operating characteristic analysis) were more common in the spasm group (93% versus 28%, P<0.01), as was negative remodeling (67% versus 11%, P<0.01). Multivariable analysis revealed noncalcified (odds ratio [OR], 48.7; 95% CI, 8.81-269; P<0.01), intermediate attenuation (OR, 19.3; 95% CI, 4.96-75.4; P<0.01); negative remodeling (OR, 8.83; 95% CI, 2.87-27.2; P<0.01); and male sex (OR, 4.55; 95% CI, 1.24-16.6; P=0.02) as predictors of the plaque associated with coronary spasm. CONCLUSIONS: MSCT can detect differences in individual plaque composition and morphology among atherosclerotic plaques without significant luminal narrowing in areas of inducible vasospasm compared to areas without vasospasm.