Tim Schäufele

Clinical Usefulness, Angiographic Characteristics, and Safety Evaluation of Intracoronary Acetylcholine Provocation Testing Among 921 Consecutive White Patients With Unobstructed Coronary Arteries

Background— Coronary spasm can cause myocardial ischemia and angina in patients with and those without obstructive coronary artery disease. However, provocation tests using intracoronary acetylcholine administration are rarely performed in clinical routine in the United States and Europe. Thus, we assessed the clinical usefulness, angiographic characteristics, and safety of intracoronary acetylcholine provocation testing in white patients with unobstructed coronary arteries. Methods and Results— From September 2007 to June 2010, a total of 921 consecutive patients (362 men, mean age 62±12years) who underwent diagnostic angiography for suspected myocardial ischemia and were found to have unobstructed coronary arteries (no stenosis ≥50%) were enrolled. The intracoronary acetylcholine provocation testing was performed directly after angiography according to a standardized protocol. Three hundred forty-six patients (35%) reported chest pain at rest, 222 (22%) reported chest pain on exertion, 238 (24%) reported a combination of effort and resting chest pain, and 41 (4%) presented with troponin-positive acute coronary syndrome. The overall frequency of epicardial spasm (>75% diameter reduction with angina and ischemic ECG shifts) was 33.4%, and the overall frequency of microvascular spasm (angina and ischemic ECG shifts without epicardial spasm) was 24.2%. Epicardial spasm was most often diffuse and located in the distal coronary segments (P<0.01). No fatal or irreversible nonfatal complications occurred. However, 9 patients (1%) had minor complications (nonsustained ventricular tachycardia [n=1], fast paroxysmal atrial fibrillation [n=1], symptomatic bradycardia [n=6], and catheter-induced spasm [n=1]). Conclusions— Epicardial and microvascular spasm are frequently found in white patients with unobstructed coronary arteries. Epicardial spasm is most often diffuse and located in the distal coronary segments. The intracoronary acetylcholine provocation test is a safe technique to assess coronary vasomotor function.

Exercise-Induced Spastic Coronary Artery Occlusion at the Site of a Moderate Stenosis Neither Prinzmetal's Angina nor Cardiac Syndrome X but “Prinzmetal X”

A 44-year-old man was referred to our hospital to undergo coronary angiography because of suspected coronary artery disease. For approximately 2 weeks, the patient had been experiencing typical symptoms of angina pectoris that occurred exclusively during physical exercise and predominantly in the morning hours when he bicycled to work. His general practitioner had performed a bicycle exercise test. In his written report, the practitioner noted that he suspected hemodynamically significant coronary artery disease because of reproduction of typical angina pectoris in addition to ischemic ECG changes. On admission, the patient was in good general condition with no symptoms at rest. Coronary angiography revealed an ≈80% stenosis in the small right coronary artery and an ≈50% stenosis in the proximal segment of the left anterior descending artery (LAD), although systolic left ventricular function was normal (Figure 1). Fractional flow measurements (fractional flow reserve) were performed in the right coronary artery and the LAD and revealed a significantly impaired fractional flow reserve only in the right coronary artery (fractional flow reserve 70%) and not in the LAD (fractional flow reserve 85%). Thus, the right coronary artery stenosis was treated with a drug-eluting stent (Figure 1), and the patient was discharged on medical therapy. Figure 1. Coronary angiograms of the left coronary artery (LCA) and right coronary artery (RCA) at first presentation. A stenosis of ≈50% was observed in the proximal segment of the LAD (left; black arrow), and an ≈80% stenosis was observed in the RCA (middle; black arrow). The stenosis of the RCA was stented successfully with a drug-eluting stent (right; black arrow). PCI indicates percutaneous coronary intervention. Six weeks later, the patient was referred again to our department because of unchanged symptoms of exercise-induced …

Cerebral Embolic Protection Devices During Transcatheter Aortic Valve Implantation

Background and Purpose— Silent ischemic embolic lesions are common after transcatheter aortic valve implantation (TAVI). The use of embolic protection devices (EPD) may reduce the occurrence of these embolic lesions. Thus, a quantitative overview and credibility assessment of the literature was necessary to draw a robust message about EPD. Therefore, the aim of this meta-analysis was to study whether the use of EPD reduces silent ischemic and clinically evident cerebrovascular events associated with TAVI. Methods— We conducted a comprehensive search to identify studies that evaluated patients undergoing TAVI with or without EPD. Random-effects meta-analyses were performed to estimate the effect of EPD compared with no-EPD during TAVI using aggregate data. Results— Sixteen studies involving 1170 patients (865/305 with/without EPD) fulfilled the inclusion criteria. The EPD delivery success rate was reported in all studies and was achieved in 94.5% of patients. Meta-analyses evaluating EPD versus without EPD strategies could not confirm or exclude any differences in terms of clinically evident stroke (relative risk, 0.70; 95% confidence interval [CI], 0.38–1.29; P=0.26) or 30-day mortality (relative risk, 0.58; 95% CI, 0.20–1.64; P=0.30). There were no significant differences in new-single, multiple, or total number of lesions. The use of EPD was associated with a significantly smaller ischemic volume per lesion (standardized mean difference, −0.52; 95% CI, −0.85 to −0.20; P=0.002) and smaller total volume of lesions (standardized mean difference, −0.23; 95% CI, −0.42 to −0.03; P=0.02). Subgroup analysis by type of valve showed an overall trend toward significant reduction in new lesions per patient using EPD (standardized mean difference, −0.41; 95% CI, −0.82 to 0.00; P=0.05), driven by self-expanding devices. Conclusions— The use of EPD during TAVI may be associated with smaller volume of silent ischemic lesions and smaller total volume of silent ischemic lesions. However, EPD may not reduce the number of new-single, multiple, or total number of lesions. There was only very low quality of evidence showing no significant differences between patients undergoing TAVI with or without EPD with respect to clinically evident stroke and mortality.

Acetylcholine-induced coronary spasm in patients with unobstructed coronary arteries is associated with elevated concentrations of soluble CD40 ligand and high-sensitivity C-reactive protein.

Objectives To assess whether epicardial and microvascular coronary artery spasm in response to acetylcholine (ACH) is associated with markers of inflammation, platelet stimulation, and endothelial activation in patients with angina and unobstructed coronary arteries. Background Patients with angina pectoris despite angiographically normal coronary arteries represent a diagnostic and therapeutic challenge. Both impaired coronary microvascular dilatory responses as well as diffuse distal epicardial and microvascular coronary artery spasm have been described as possible pathogenic mechanisms. Although inflammation has been proposed to play a pathogenic role in angina, an association between ACH-induced coronary vasospasm and inflammation in Caucasians has not been reported previously in this context. Patients and methods We assessed 62 consecutive patients (26 men, age 60±10 years) with chest pain despite angiographically unobstructed coronary arteries (<50% stenosis) who underwent intracoronary ACH testing for the diagnosis of coronary artery spasm. High-sensitivity C-reactive protein (hs-CRP), e-selectin, neopterin, and sCD40L concentrations were measured in all patients before ACH testing. The ACH test was considered to be ‘positive’ in the presence of (a) angina and at least 75% coronary diameter reduction (epicardial coronary artery spasm) or (b) ischemic ST-shifts and angina in the absence of epicardial spasm (microvascular spasm). Eight patients without angina pectoris served as a control group. Results The ACH test was positive in 48 patients (77%). Twenty-seven patients had epicardial spasm (56%) and 21 patients had microvascular spasm (44%). Epicardial spasm was diffuse in 26 patients (96%) and focal in one patient (4%). Elevated hs-CRP, e-selectin, and sCD40 ligand concentrations were significantly (P⩽0.05) associated with a positive ACH-test response. Hs-CRP (odds ratio 1.54, confidence interval 1.02–2.33, P=0.04) and sCD40 ligand (odds ratio 1.001, confidence interval 1.00–1.001, P=0.003) were predictors for a positive ACH test on multivariate analysis. None of the patients in the control group developed epicardial or microvascular spasm during ACH testing. Conclusion Epicardial and microvascular coronary spasm in response to ACH correlate significantly with hs-CRP and sCD40 ligand concentrations in patients with angina pectoris and angiographically unobstructed coronary arteries. These results suggest that an association exists between inflammation and coronary artery spasm in patients with angina pectoris despite unobstructed coronary arteries and studies are needed to explore the mechanisms underlying this association.

Conventional versus Transapical Aortic Valve Replacement: Is It Time for Shift in Indications?

Background The incidence of degenerative aortic valve diseases has increased along with the life expectancy of our population. Although conventional aortic valve replacement (AVR) is the gold standard for symptomatic aortic stenosis, transcatheter procedures have proven to be a valid therapeutic option in high‐risk patients. The aim of this study was to compare these procedures in a high‐risk cohort. Methods We retrospectively analyzed all symptomatic (dyspnea or angina) high‐risk patients (logistic EuroSCORE ≥ 15%) fulfilling the transcatheter aortic valve implantation (TAVI) indications. Most of the AVR patients (n = 180) were operated on before the implementation of TAVI. All TAVI procedures (n = 127) were performed transapically (TA). After matching for age, logistic EuroSCORE, and left ventricular ejection fraction, 82 pairs of patients were evaluated. Results When comparing AVR with TA‐TAVI, there was no difference between groups in survival after 1 year (Kaplan‐Meier analysis, 81.1% [95% CI: 72.5‐89.7%] vs. 75.8% [95% CI: 66.2‐75.9%], Log tank p = 0.660) and the complication rates (n for AVR vs. TA‐TAVI: stroke, 2 vs. 0, p = 0.580; acute renal insufficiency, 8 vs. 12, p = 0.340; atrial fibrillation, 24 vs. 26, p = 0.813; pacemaker implantation, 4 vs. 4, p > 0.999). In addition, quality of life did not differ between groups. Patients in the TA‐TAVI group had lower mean valvular gradients postoperatively compared with the AVR group (14.6 ± 6.6 vs. 10.2 ± 4.9 mm Hg, p < 0.001). Conclusion For high‐risk patients, the TAVI procedure is comparable with conventional AVR, but is not advantageous. These results do not support the expansion of TAVI to low‐ or intermediate‐risk patients.

Testing in Patients With Stable Coronary Artery Disease - The Debate Continues.

The major guidelines on stable coronary artery disease recommend revascularizing patients with large areas of myocardium at risk. The algorithms on how to prove that such high risk is present differ considerably. The opinions on the use of coronary CT (calcium scoring and angiography) vary widely. This review aims to summarize the recommendations of the major guidelines, commenting on differences between the guidelines and discussing whether extending the role of coronary CT angiography should be considered in the light of new CT data.

Predictors of outcome in patients with parvovirus B19 positive endomyocardial biopsy.

Objective Primary objective was to establish the prognostic value of the myocardial load of PVB19 genomes in patients presenting for work-up of myocarditis and/or unclear cardiomyopathy in comparison to clinical, and CMR parameters.

Response to Letters Regarding Article, “Clinical Usefulness, Angiographic Characteristics, and Safety Evaluation of Intracoronary Acetylcholine Provocation Testing Among 921 Consecutive White Patients With Unobstructed Coronary Arteries”

We thank Dr Mohri for his insightful comments. We completely agree with Dr Mohri that standardization of intracoronary provocation testing for coronary spasm with respect to dosage, infusion time, and a route of administration is urgently needed, as mentioned in our article.1 As highlighted in the Methods section of our article, the maximum dosage of 200 μg acetylcholine for the left coronary artery was derived from the Evaluation of Nifedipine on Coronary Endothelial Function (ENCORE) study. In this trial, the dose for the left anterior descending artery and for the left circumflex artery was 100 μg in each vessel injected via a selective catheter in a coronary segment without significant coronary artery disease. In the most constricting segment, this dose of acetylcholine reduced the coronary diameter …

Transradial Approach for Left Ventricular Endomyocardial Biopsy

BACKGROUND Left ventricular endomyocardial biopsy (LV-EMB) may offer a superior diagnostic yield compared with right ventricular endomyocardial biopsy (RV-EMB) in conditions predominantly affecting the LV but is underused compared with RV-EMB. Despite the steep uptake of radial approach in coronary interventions, LV-EMB is usually performed via the femoral artery in contemporary practice. Therefore, the aim of this study was to assess the safety and feasibility of LV-EMB via a transradial approach in a multicentre registry. METHODS One-hundred and two patients who underwent LV-EMB via transradial approach were included. Clinical characteristics, procedural, safety and feasibility data were evaluated. RESULTS LV-EMB was successfully performed via transradial access in 101 (99%) patients. Mild or moderate radial artery spasm occurred in 12 (12%) patients, but only 1 (0.98%) patient required conversion to femoral access due to severe spasm. A total of 80 (78%) patients had LV-EMB via a sheathless guide catheter. Among those, 77 (96.3%) patients had 7.5-French sheathless guides, and 3 (3.8%) patients had 8.5-French sheathless guides inserted. Radial sheaths were used in the remaining 22 patients, with 5-French sheaths in 21 of 22 patients. Heparin was administered to 93.1% of patients at a median dose of 5000 (3000-5000) IU. The remaining patients followed a provisional strategy upon patent hemostasis achievement. No access site-related complications were reported. There were no major complications (pericardial tamponade, life-threatening arrhythmia, cerebrovascular accident or death). CONCLUSIONS In a population of patients undergoing transradial LV-EMB, the procedural success rate was high and showed an excellent safety profile. Further studies comparing transradial and transfemoral routes may help expand the use of transradial access for LV-EMB.

Diagnostic capability of CMR for the diagnosis of acute myocarditis in young patients is determined by the presence of elevated cardiac enzymes

Summary Only in patients with elevated levels of cardiac troponin CMR can reliably corroborate the clinical diagnosis of acute myocarditis Background Diagnosis of myocarditis remains a difficult clinical challenge, since the clinical spectrum of myocarditis is multifaceted. As clinical presentation and ECG-changes tend to be non-specific, cardiovascular magnetic resonance (CMR) has proven to be av aluable diagnostic tool regarding non-invasive diagnosis of myocarditis. However, CMR studies are time- and cost-intensive. Hence, further parameters are warranted to identify those individuals in whom a CMR study is likely to add crucial information regarding correct and timely diagnosis of acute myocarditis. The current study sought to elucidate the diagnostic yield of CMR in young patients aged ≤ 40 yrs with clinical diagnosis of myocarditis based on symptoms and ECG in relation to the presence or absence of elevated levels of cardiac troponin as an additional marker of acute myocardial injury. Methods Between 2009 and 2011, young patients aged ≤ 40 yrs presenting with acute or subacute chest pain and significant new-onset ST-segment changes suggestive of myocarditis, prospectively underwent CMR studies after obstructive coronary artery disease (CAD) was ruled out by coronary angiography if risk factors were present. Black-blood T2-weighted turbo-spin-echo (TSE) sequences were obtained to detect myocardial edema. Late gadolinium enhancement (LGE) imaging was performed in order to detect focal areas of contrast enhancement. Studies were performed on a 1.5 Tesla MR-Scanner (Siemens Sonata). Results During the recruitment period, 106 consecutive patients aged 17 to 40 yrs were included. Mean age was 29±7 yrs. In 19 patients additional cardiac catheterization was performed in order to definitely rule out obstructive CAD. LGE was successfully performed in all patients while in one patient T2-weighted edema images could not be obtained due to insufficient image quality. 13 (12%) patients showed significantly elevated levels of cardiac troponin. 15 (14%) patients showed focal late gadolinium enhancement (LGE) indicating myocarditis. All patients (100%) who presented with elevated levels of troponin showed presence of focal LGE. T2-weighted edema imaging showed correlating myocardial edema in 7 of these 13 individuals (54%). However, none of the 2 patients demonstrating LGE in the absence of elevated cardiac enzymes had signs of myocardial edema assessed by T2-weighted edema imaging but both turned out to have anamnestic evidence of subsided myocarditis in the past requiring exclusion of “acute” myocarditis. Moreover, the remaining 91 young patients with an unequivocal clinical diagnosis of myocarditis - but normal troponin levels - demonstrated normal findings by both T2-weighted edema and LGE imaging.