Citations

Ischemic symptoms may be explained by a multitude of coronary pathologies, including coronary artery tortuosity, atherosclerosis, fibromuscular dysplasia, vasculitis, coronary vasospasm, or microvascular disease. We present an unusual case of coronary kinking in a patient presenting with exertional jaw pain in the absence of atherosclerotic risk factors. Multimodality imaging, coronary imaging, and coronary physiology helped establish the diagnosis and guide management.

ABSTRACT Aims Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. Methods and results A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85–0.92), a sensitivity of 0.85 (0.78–0.95) and a specificity of 0.76 (0.74–0.79) in the internal validation cohort and an AUC of 0.82 (0.73–0.91), a sensitivity of 0.74 (0.61–0.87) and a specificity of 0.79 (0.77–0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort. Conclusion A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death.

BACKGROUND: The financial burden linked to the diagnosis and treatment of patients with chest pain on the health care system is considerable. Angina and nonobstructive coronary artery disease (ANOCA) is common, associated with adverse cardiovascular events, and may lead to repeat testing or hospitalizations. Diagnostic certainty can be achieved in patients with ANOCA using coronary reactivity testing (CRT); however, its financial effect on the patient has not been studied. Our goal was to assess the effect of CRT on health care–related cost in patients with ANOCA. METHODS: Patients with ANOCA who underwent diagnostic coronary angiography (CAG) and CRT (CRT group) were matched to controls who had similar presentation but only underwent a CAG without CRT (CAG group). Standardized inflation-adjusted costs were collected and compared between the 2 groups on an annual basis for 2 years post the index date (CRT or CAG). RESULTS: Two hundred seven CRT and 207 CAG patients were included in the study with an average age of 52.3±11.5 years and 76% females. The total cost was significantly higher in the CAG group as compared with the CRT group ($37 804 [$26 933–$48 674] versus $13 679 [$9447–$17 910]; P <0.001). When costs are itemized and divided based on the Berenson-Eggers Type of Service categorization, the largest cost difference occurred in imaging (any type, including CAG; P <0.001), procedures (eg, percutaneous coronary intervention/coronary artery bypass grafting/thrombectomy) ( P =0.001), and test (eg, blood tests, EKG; P <0.001). CONCLUSIONS: In this retrospective observational study, assessment of CRT in patients with ANOCA was associated with significantly reduced annual total costs and health care utilization. Therefore, the study may support the integration of CRT into clinical practice.

Aims Guidelines for suspected cardiac chest pain have used historical risk stratification tools, advocating invasive coronary angiography (ICA) first-line in those at highest risk. We aimed to determine whether different strategies to manage suspected stable angina affected medium-term cardiovascular event rates and patient-reported quality of life (QoL) measures. Methods CE-MARC 2, a three-arm parallel group trial, randomised patients with suspected stable cardiac chest pain and a Duke Clinical pretest likelihood of coronary artery disease between 10% and 90%. Patients were randomised to either first-line cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT) or the UK National Institute for Health and Care Excellence (NICE) CG95 (2010) guidelines-directed care. For the three arms, 1-year and 3-year first major adverse cardiovascular event (MACE) rates and QoL assessed by the Seattle Angina Questionnaire, Short Form 12 (V.12) Questionnaire and EuroQol-5 Dimension Questionnaire were recorded. Results 1202 patients were randomised to CMR (n=481), SPECT (n=481) and NICE (n=240). Forty-two patients (18 CMR, 18 SPECT, 6 NICE) experienced one or more MACEs. The percentage rates (95% CIs) of MACE in the CMR, SPECT and NICE groups at 3 years were 3.7% (2.4%, 5.8%), 3.7% (2.4%, 5.8%) and 2.1% (0.9%, 4.8%), respectively. QoL scores did not significantly differ across domains. Conclusion Despite a fourfold increase in referrals for ICA, the NICE CG95 (2010) guidelines risk-stratified care strategy did not significantly reduce 3-year MACE or improve QoL, as compared with functional imaging with CMR or SPECT. Trial registration number ClinicalTrials.gov Registry (NCT01664858).

Background A growing body of evidence links coronary artery atherosclerosis and calcification to osteoporosis in women. Coronary endothelial dysfunction (CED) is associated with adverse cardiovascular events. We aimed to study the association of CED and development of osteoporosis. Methods Coronary vascular reactivity was evaluated in 225 women, greater than age 50, with non-obstructive coronary arteries, by administration of intracoronary acetylcholine during diagnostic angiography. CED was defined as <50% increase in coronary blood flow (CBF) from baseline in response to maximal dose. After a median follow-up of 7 years, patients were assessed by a questionnaire for development of osteoporosis. Results The average age of the cohort was 60 years. Of 225 women, 60% (135) had CED. 18.2% (41 of 225 women) developed osteoporosis during follow-up. Women with CED were twice more likely to develop osteoporosis vs. women without CED (23% vs. 11.1%, p=0.024). Women who developed osteoporosis compared to those who did not had a markedly lower response (% change) in CBF: median (IQR)-4.3 (-28.3, 51.7) vs. 39.9 (-8.2, 106.0), p=0.007. In univariate analysis, CED was significantly associated with development of osteoporosis (p=0.024, relative risk 2.07, 95% CI: 1.07, 4.00). Multivariate analysis indicated CED as an independent predictor of osteoporosis (p=0.04). Discussion Endothelial dysfunction may account for or share similar mechanisms with development of osteoporosis in cardiac patients.

Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. Methods: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×10 5 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. Results: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [−18.0 to 32.4] to 57.6 [16.3–98.3]%; P =0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P =0.00018), and sublingual nitroglycerin use/day (1 [0.4–3.5] to 0 [0–1], Wilcoxon signed-rank test, P =0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. Conclusions: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03471611.

Abstract Background The SARS-CoV-2 pandemic has led to the development of the first mRNA vaccines used in humans. The vaccines are well tolerated, safe, and highly efficacious; however, post-marketing surveillance is revealing potential rare adverse effects. We report a case of symptomatic acute myocarditis following administration of the second dose of mRNA-1273 SARS-CoV-2 vaccine. Case summary A 44-year-old man presented with chest pain and ST-segment elevation 4 days after receiving the second dose of mRNA-1273 SARS-CoV-2 Vaccine. Emergent coronary angiogram showed minimal coronary artery disease. Cardiac magnetic resonance imaging confirmed acute myocarditis. Diagnosis of vaccine-associated myocarditis was made given the temporal relationship and supportive treatment initiated. Follow-up at 1 month confirmed complete symptomatic recovery and echocardiogram demonstrated normalization of cardiac function. Discussion Acute myocarditis should be considered in patients who present with chest pain or dyspnoea within days of receiving mRNA-1273 SARS-CoV-2 vaccination, especially after the second dose. This may be managed successfully with supportive therapies with complete recovery of cardiac function and symptoms. Further research is warranted to determine the mechanisms by which mRNA vaccines may cause myocarditis and for potential long-term cardiovascular injury.

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher ( P <0.001), and there were fewer women ( P =0.046) in the AF than in the non‐AF group. Left ventricular ejection fraction was significantly lower ( P =0.001), and cardiogenic shock was more often observed ( P <0.001) in the AF group. Both in‐hospital ( P <0.001) and long‐term mortality ( P <0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long‐term mortality (hazard ratio, 2.31; 95% CI, 1.50–3.55; P <0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in‐hospital and long‐term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in‐hospital and long‐term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01947621.

Introduction: Thoracic external beam radiation therapy (XRT) for cancer is associated with a multitude of long-term cardiotoxic side effects. Previous studies have suggested worse outcomes in XRT-treated cancer survivors who undergo revascularization with CABG, but sample sizes have been small. In addition, XRT after CABG is thought to portend decreased patency and survival. We aimed to examine outcomes after CABG in patients with XRT compared with to those without XRT. Methods: We identified all patients who were treated with both CABG (between 1999 and 2013) and curative thoracic XRT for cancer (between 1971 and 2013) (>30 Gray). Baseline clinical characteristics and comorbidities at time of CABG, as well as long-term outcomes after CABG and XRT were compared with propensity matched control cohorts. Results: A total of 38 patients underwent CABG following XRT [Group 1] (mean age 67.9, 63% female) and 43 patients underwent XRT after CABG [Group 2] (mean age 69.3, 63% female). Compared with propensity-matched controls (Group 1: n=141; Group 2: n=167), baseline clinical and demographic characteristics between cases and controls were similar in both groups, except a lower incidence of triple vessel disease in XRT cases in Group 2 (64 vs 80%, p=0.02). For Group 1, there was no significant difference in all-cause survival in long-term follow-up after CABG (Fig. 1, p=0.72). Meanwhile, Group 2 cases had significantly higher all-cause mortality following XRT (Fig. 2, p<0.001). Conclusions: Patients previously treated with thoracic XRT who subsequently undergo CABG for coronary artery disease have a similar overall mortality rate compared to patients without prior XRT. This suggests that CABG is an effective method of revascularization in these patients. The higher mortality rates in CABG patients who subsequently develop disease requiring thoracic XRT is likely due to oncologic rather than cardiovascular causes, but more data are necessary to evaluate this finding.