Jelena R. Ghadri

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy

BACKGROUND The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and post-procedural comparison with the Simplicity® catheter system and the EnligHTN™ multi-electrode renal denervation catheter

Aims Catheter-based renal nerve ablation (RNA) using radiofrequency energy is a novel treatment for drug-resistant essential hypertension. However, the local endothelial and vascular injury induced by RNA has not been characterized, although this importantly determines the long-term safety of the procedure. Optical coherence tomography (OCT) enables in vivo visualization of morphologic features with a high resolution of 10–15 µm. The objective of this study was to assess the morphological features of the endothelial and vascular injury induced by RNA using OCT. Methods and results In a prospective observational study, 32 renal arteries of patients with treatment-resistant hypertension underwent OCT before and after RNA. All pre- and post-procedural OCT pullbacks were evaluated regarding vascular changes such as vasospasm, oedema (notches), dissection, and thrombus formation. Thirty-two renal arteries were evaluated, in which automatic pullbacks were obtained before and after RNA. Vasospasm was observed more often after RNA then before the procedure (0 vs. 42%, P < 0.001). A significant decrease in mean renal artery diameter after RNA was documented both with the EnligHTN™ (4.69 ± 0.73 vs. 4.21 ± 0.87 mm; P < 0.001) and with the Simplicity® catheter (5.04 ± 0.66 vs. 4.57 ± 0.88 mm; P < 0.001). Endothelial-intimal oedema was noted in 96% of cases after RNA. The presence of thrombus formations was significantly higher after the RNA then before ablation (67 vs. 18%, P < 0.001). There was one evidence of arterial dissection after RNA with the Simplicity® catheter, while endothelial and intimal disruptions were noted in two patients with the EnligHTN™ catheter. Conclusion Here we show that diffuse renal artery constriction and local tissue damage at the ablation site with oedema and thrombus formation occur after RNA and that OCT visualizes vascular lesions not apparent on angiography. This suggests that dual antiplatelet therapy may be required during RNA.

Diagnostic Value of 13N-Ammonia Myocardial Perfusion PET: Added Value of Myocardial Flow Reserve

The ability to obtain quantitative values of flow and myocardial flow reserve (MFR) has been perceived as an important advantage of PET over conventional nuclear myocardial perfusion imaging (MPI). We evaluated the added diagnostic value of MFR over MPI alone as assessed with 13N-ammonia and PET/CT to predict angiographic coronary artery disease (CAD). Methods: Seventy-three patients underwent 1-d adenosine stress–rest 13N-ammonia PET/CT MPI, and MFR was calculated. The added value of MFR as an adjunct to MPI for predicting CAD (luminal narrowing ≥ 50%) was evaluated using invasive coronary angiography as a standard of reference. Results: Per patient, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MPI for detecting significant CAD were 79%, 80%, 91%, 59%, and 79%, respectively. Adding a cutoff of less than 2.0 for global MFR to MPI findings improved the values to 96% (P < 0.005), 80%, 93%, 89% (P < 0.005), and 92% (P < 0.005), respectively. Conclusion: The quantification of MFR in 13N-ammonia PET/CT MPI provides a substantial added diagnostic value for detection of CAD. Particularly in patients with normal MPI results, quantification of MFR helps to unmask clinically significant CAD.

Low-dose computed tomography coronary angiography with prospective electrocardiogram triggering: feasibility in a large population.

OBJECTIVES We sought to assess the feasibility of prospective electrocardiogram triggering for achieving low-dose computed tomography coronary angiography (CTCA) in a large population. BACKGROUND Prospective electrocardiogram triggering dramatically reduces radiation exposure for CTCA but requires heart rate (HR) control to obtain diagnostic image quality. Its feasibility in daily clinical routine has therefore remained to be elucidated. METHODS We evaluated 612 patients consecutively referred for CTCA by 64-slice computed tomography. Intravenous metoprolol (2 to 30 mg) was administered if necessary to achieve a target HR below 65 beats/min. Image quality was assessed on a semiquantitative 4-point scale for each coronary segment. RESULTS Forty-six (7.5%) patients were deemed ineligible due to irregular heart rhythm (n = 19), insufficient response to metoprolol (n = 21), renal insufficiency (n = 3), or inability to follow breath-hold commands (n = 3). Mean effective radiation dose was 1.8 ± 0.6 mSv with a diagnostic image quality in 96.2% of segments. Finally, low-dose CTCA allowed a firm diagnosis with regard to the presence or absence of coronary artery disease in 527 (86.1%) patients. Intravenous metoprolol to achieve an HR below 65 beats/min was used in 64.4% of patients. Incidence of nondiagnostic segments was inversely related to HR (r = -0.809, p < 0.001). Below an HR cutoff of 62 beats/min, only 1.2% of coronary segments were nondiagnostic. CONCLUSIONS Low-dose CTCA by electrocardiogram triggering is feasible in the vast majority of an every-day population. However, HR control is crucial, as an HR below 62 beats/min favors diagnostic image quality.

Coronary artery calcium scoring: Influence of adaptive statistical iterative reconstruction using 64-MDCT

OBJECTIVE Assessment of coronary artery calcification is increasingly used for cardiovascular risk stratification. We evaluated the reliability of calcium-scoring results using a novel iterative reconstruction algorithm (ASIR) on a high-definition 64-slice CT scanner, as such data is lacking. METHODS AND RESULTS In 50 consecutive patients Agatston scores, calcium mass and volume score were assessed. Comparisons were performed between groups using filtered back projection (FBP) and 20-100% ASIR algorithms. Calcium score was measured in the coronary arteries, signal and noise were measured in the aortic root and left ventricle. In comparison with FBP, use of 20%, 40%, 60%, 80%, and 100% ASIR resulted in reduced image noise between groups (7.7%, 18.8%, 27.9%, 39.86%, and 48.56%, respectively; p<0.001) without difference in signal (p=0.60). With ASIR algorithms Agatston coronary calcium scoring significantly decreased compared with FBP algorithms (837.3 ± 130.3; 802.2 ± 124.9, 771.5 ± 120.7; 744.7 ± 116.8, 724.5 ± 114.2, and 709.2 ± 112.3 for 0%, 20%, 40%, 60%, 80%, and 100% ASIR, respectively, p<0.001). Volumetric score decreased in a similar manner (p<0.001) while calcium mass remained unchanged. Mean effective radiation dose was 0.81 ± 0.08 mSv. CONCLUSION ASIR results in image noise reduction. However, ASIR image reconstruction techniques for HDCT scans decrease Agatston coronary calcium scores. Thus, one needs to be aware of significant changes of the scoring results caused by different reconstruction methods.

Validation of CT Attenuation Correction for High-Speed Myocardial Perfusion Imaging Using a Novel Cadmium-Zinc-Telluride Detector Technique

The aim of this study was to validate attenuation correction (AC) using low-dose standard CT for myocardial perfusion imaging (MPI) on a novel ultra fast γ-camera with cadmium-zinc-telluride (CZT) detector technology. Methods: Sixty-six patients (body mass index ± SD, 27.2 ± 3.5 kg/m2; range, 19.1–36.0 kg/m2) underwent a 1-d 99mTc-tetrofosmin adenosine stress–rest imaging protocol with 15-min acquisitions on a standard dual-head SPECT camera. All scans were repeated within minutes on the CZT camera, with 3-min acquisitions for stress (low dose) and 2-min acquisitions for rest (high dose) as recently established. We compared maximum myocardial uptake (20-segment model) from CZT versus standard SPECT MPI by intraclass correlation without and with CT AC. In addition, clinical agreement for each coronary territory for all scans from both devices was assessed, and Bland–Altmann (BA) limits of agreement for percentage uptake were calculated. Results: The clinical agreement between CZT and standard SPECT cameras was 96% for noncorrected low- and high-dose images (r = 0.90 and BA = −18 to 15, and r = 0.91 and BA = −15 to 16, respectively), and agreement after AC was 96% for low- and 99% for high-dose images (r = 0.87 and BA = −16 to 14, and r = 0.88 and BA = −16 to 14, respectively). Conclusion: Our results support that AC of MPI on the novel CZT camera, compared with AC MPI on a conventional SPECT camera, is feasible because it provides a high correlation of segmental tracer uptake and an excellent clinical agreement.

Happy heart syndrome: role of positive emotional stress in takotsubo syndrome

Abstract Aims Takotsubo syndrome (TTS) is typically provoked by negative stressors such as grief, anger, or fear leading to the popular term ‘broken heart syndrome’. However, the role of positive emotions triggering TTS remains unclear. The aim of the present study was to analyse the prevalence and characteristics of patients with TTS following pleasant events, which are distinct from the stressful or undesirable episodes commonly triggering TTS. Methods and results Takotsubo syndrome patients with preceding pleasant events were compared to those with negative emotional triggers from the International Takotsubo Registry. Of 1750 TTS patients, we identified a total of 485 with a definite emotional trigger. Of these, 4.1% (n = 20) presented with pleasant preceding events and 95.9% (n = 465) with unequivocal negative emotional events associated with TTS. Interestingly, clinical presentation of patients with ‘happy heart syndrome’ was similar to those with the ‘broken heart syndrome’ including symptoms such as chest pain [89.5% (17/19) vs. 90.2% (412/457), P = 1.0]. Similarly, electrocardiographic parameters, laboratory findings, and 1-year outcome did not differ. However, in a post hoc analysis, a disproportionate higher prevalence of midventricular involvement was noted in ‘happy hearts’ compared with ‘broken hearts’ (35.0 vs. 16.3%, P = 0.030). Conclusion Our data illustrate that TTS can be triggered by not only negative but also positive life events. While patient characteristics were similar between groups, the midventricular TTS type was more prevalent among the ‘happy hearts’ than among the ‘broken hearts’. Presumably, despite their distinct nature, happy and sad life events may share similar final common emotional pathways, which can ultimately trigger TTS.

Takotsubo cardiomyopathy: still much more to learn

Takotsubo cardiomyopathy (TTC) was first described in 1990 when Japanese cardiologists from the Hiroshima Asa General Hospital published their findings in a chapter of a Japanese medical text. At that time, TTC was completely unrecognised in Europe and North America, and for years the disorder was thought to affect only Asians. Then in 2003, the first study of TTC in Caucasians indicated that this was actually a widespread affliction.1 By 2013, the number of publications related to TTC had risen to 1879, a number mirroring increased awareness and interest in this disease. But while numerous case reports of TTC exist in the literature, large systematic registries or trials are lacking. The main characteristic of TTC is transient, reversible, systolic dysfunction of the left ventricle. Relatively little definitive information is available otherwise, and as a result many cases likely remain unreported and often misdiagnosed, frequently as acute coronary syndrome (ACS). In particular, TTC may remain unrecognised if symptomatic patients do not undergo corroborating coronary angiography. In this regard, it is likely that subclinical or mild cases of TTC exist, but remain unidentified due to limited diagnostic workup, particularly in centres without primary percutaneous coronary intervention facilities. Not surprisingly, the exact prevalence remains unknown. However, it is estimated that TTC affects approximately 2% of patients presenting as ACS. Rates of TTC in women with ACS are suggested to be higher at 5.9–7.5%.2 ,3 By searching for the International Classification of Diseases, ninth revision, code 429.83, among 33 506 402 hospitalisations in a nationwide inpatient sample database, Deshmukh et al 4 found that 6837 patients in the USA were diagnosed with TTC during 2008, accounting for 0.02% of all hospitalisations that year. Nevertheless, we do not know if cases in the nationwide inpatient sample database were misdiagnosed, wrongly classified, or unrecognised and …

Very high coronary calcium score unmasks obstructive coronary artery disease in patients with normal SPECT MPI.

Objectives To study the clinical impact of a very high coronary artery calcium score (CAC >1000) in patients with no known coronary artery disease (CAD) and normal single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). The secondary aim was to evaluate whether triple vessel disease would support the notion of balanced ischaemia as an underlying mechanism of false negative SPECT MPI in patients with very high CAC. Background No data exist on the clinical value of high CAC in patients with normal SPECT MPI. Methods 50 patients with suspected CAD and normal stress/rest SPECT MPI and CAC >1000 prospectively underwent invasive coronary angiography as the standard of reference. Coronary lesions with ≥50% luminal diameter narrowing on invasive coronary angiography were considered to represent significant stenosis. Results The median total CAC was 1975 (range 1018–8046). In 37/50 (74%) patients, coronary angiography revealed one-vessel disease (1-VD) (n=15), 2-VD (n=10) or 3-VD (n=12). Twenty-six revascularisations (percutaneous coronary intervention/coronary artery bypass grafting) were performed in seven (6/1), seven (6/1) and 12 (7/5) patients with 1-VD, 2-VD and 3-VD, respectively. Conclusions In patients with normal SPECT MPI, a CAC >1000 confers a high diagnostic added value for detecting CAD. This is not solely based on unmasking balanced ischaemia due to epicardial 3-VD, as it occurred predominantly in patients with 1-VD and 2-VD.

Semiconductor Detectors Allow Low-Dose–Low-Dose 1-Day SPECT Myocardial Perfusion Imaging

Cadmium zinc telluride (CZT) detectors with linear counting rate response enable count subtraction in sequential scanning. We evaluated whether count subtraction eliminated the need for higher activity doses in the second part of the 1-d stress–rest myocardial perfusion imaging (MPI) protocol. Methods: For 50 patients (mean age ± SD, 66 ± 12 y) with visually abnormal (n = 42) or equivocal (n = 8) adenosine-stress MPI (320 MBq of 99mTc-tetrofosmin) on a CZT camera, rest MPI was performed with a low dose (320 MBq) and repeated after injection of an additional 640 MBq of 99mTc-tetrofosmin to achieve a standard 3-fold increased dose at rest (960 MBq), compared with stress (320 MBq). Low-dose rest myocardial perfusion images were reconstructed after subtracting the background activity of the preceding stress scan. Segmental percentage tracer uptake of the 2 rest myocardial perfusion images (320 vs. 960 MBq) was compared using intraclass correlation and Bland–Altman limits of agreement. Patient- and coronary territory–based clinical agreement was assessed. Results: The standard protocol revealed ischemia in 34 (68%) and a fixed defect in 8 (16%) patients, of whom 33 (97%) and 8 (100%) were correctly identified by low-dose MPI (clinical agreement, 98%). Segmental uptake correlated well between low- and standard-dose rest scans (r = 0.94, P < 0.001; Bland–Altman limits of agreement, −11 to +11%). Defect extent was 14.4% (low-dose) versus 13.1% (standard-dose) at rest (P = not statistically significant) and 26.6% at stress (P < 0.001 vs. rest scans). Conclusion: These promising results suggest that accurate assessment of ischemic myocardial disease is feasible with a low-dose–low-dose 1-d SPECT MPI protocol using a CZT device.