Stress myocardial blood flow reduced after severe COVID-19, not related to symptoms

Introduction Persistent cardiopulmonary symptoms after COVID-19 are reported in a large number of patients and the underlying pathology is still poorly understood. (1) Histopathologic studies revealed myocardial macrophage infiltrates in deceased patients, likely an unspecific finding of severe illness, and increased prevalence of micro- and macrovascular thrombi. (2) We examined whether microvascular perfusion, measured by quantitative cardiac magnetic resonance under vasodilator stress, was altered post COVID-19. Methods Our population consisted of 12 patients from the Pa-COVID-19-Study of the Charité Berlin, which received a cardiac MRI as part of a systematic follow up post discharge, 10 patients that presented at the German Heart Center Berlin with persistent cardiac symptoms post COVID-19 and 12 patients from the Kings College London referred for stress MRI and previous COVID-19. The scan protocol included standard functional, edema and scar imaging and quantitative stress and rest perfusion to assess both macro- and microvascular coronary artery disease. The pharmacological stress agent was regadenosone in 20 and adenosine in 13 of the patients. To control for the higher heart rate increase under regadenosone compared to adenosine, we calculated the myocardial blood flow per heartbeat (MBF_HRi) under stress. Results The median time between first positive PCR for COVID-19 and the CMR exam was 2 months (Range 0 to 12). None of the 33 patients exhibited signs of myocardial edema. One patient with a previous history of myocarditis had focal fibrosis. Three patients with known coronary artery disease showed ischemic Late Enhancement. Five patients had a small pericardial effusion; one of these four patients showed slight focal pericardial edema and LGE, consistent with mild focal pericarditis. Five Patients had a stress-induced focal perfusion deficit. Mean Stress MBF_HRi was 32.5±6.5 μl/beat/g. Stress MBF_HRi was negatively correlated with COVID-19 severity (rho=−0.361, P=0.039) and age (r=−0.452, P=0.009). The correlation with COVID-19 severity remained significant after controlling for age (rho=−0.390, P=0.027). There was no apparent difference in stress MBF_HRi between patients with and without persistent chest pain (34.5 vs. 31.5 μl/beat/g, P=0.229) Conclusion While vasodilator-stress myocardial blood flow after COVID-19 was negatively correlated to COVID-19 severity, it was not correlated to the presence of chest pain. The etiology of persistent cardiac symptoms after COVID-19 remains unclear. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Philips Figure 1. A) Quantitative regadenosone stress myocardial blood flow (MBF) map, medial short axis slice, in a patient with persistent cardiac symptoms after COVID-19. B) Boxplot of stress MBF per heart beat by COVID-19 severity, showing decreasing MBF with increasing COVID-19 severity.

Additive prognostic value of coronary flow and heart rate reserve during vasodilator stress echocardiography in hypertrophic cardiomyopathy

Background Coronary flow velocity reserve (CFVR) and heart rate reserve (HRR) during vasodilator stress echocardiography (SE) assess coronary microvascular function and cardiac sympathetic reserve respectively. Both CFVR and HRR can be impaired in hypertrophic cardiomyopathy (HCM). Objectives To evaluate the prognostic value of CFVR and HRR during vasodilator SE in HCM. Methods We enrolled 244 HCM patients (age=51±15 years, 116 men) studied with vasodilator SE from 1999 to 2019 in 5 certified centers. Stress modality was either adenosine (Ado, 0.14 mg/kg/min in 2', n=171) or dipyridamole (Dip, 0.84 mg/kg in 6', n=73). Left ventricular outflow tract obstruction was present at rest in 80 patients (33%). We assessed CFVR in left anterior descending coronary artery (by TTE in 225, and TEE in 19 patients) and HRR (peak/rest heart rate). Abnormal values of HRR were based on receiver operating characteristics for Ado and Dip separately calculated. All patients completed the follow-up. Results CFVR was 2.17±0.46 for Dip and 2.13±0.43 for Ado (p=ns); HRR was 1.36±0.19 for Dip and 1.10±0.16 for Ado (p<0.001). An abnormal CFVR (<2.0 for both Ado and Dip) was present in 28 patients for Dip and 73 for Ado (38% vs 43%, p=ns). An abnormal HRR (≤1.34 for Dip and ≤1.03 for Ado) was present in 39 patients for Dip and in 70 patients for Ado (53% vs 41%, p=ns). During a median follow-up of 67 months (interquartile range: 29–103 months), 97 spontaneous events occurred in 71 patients: 29 all-cause deaths, 32 new hospital admission for acute heart failure, 3 sustained ventricular tachycardias, 32 atrial fibrillations and 1 heart transplantation. Event rate was 2.5%/year in patients with normal CFVR and HRR, 4.7%/year in patients with only one abnormal criterion and 10.9%/year in patients with abnormal responses of both criteria (see figure). At multivariate analysis, abnormality of both CFVR and HRR (Hazard ratio 4.033, 95% CI 1.863–8.729, p<0.001) was independent predictor of events. Conclusions A reduced CFVR and blunted HRR during vasodilator SE identify distinct phenotypes and show independent value in predicting outcome in HCM patients. FUNDunding Acknowledgement Type of funding sources: None. Figure 1. Kaplan-Meier spontaneous event-free survival curves based on HRR and CFVR. Kaplan-Meier survival curves (considering spontaneous events) in patients stratified with the abnormal HRR and/or CFVR. Number of patients at risk per year is shown.

Prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance after inconclusive stress testing

Background While current guidelines recommend noninvasive testing to detect coronary artery disease, stress tests are deemed inconclusive in a quarter of cases. The strategy for risk stratification after inconclusive stress testing is not well standardized. To assess the prognostic value of vasodilator stress cardiovascular magnetic resonance (CMR) parameters and CMR-based coronary revascularization in patients after inconclusive stress testing. Methods Between 2008 and 2020, consecutive patients with a first non-CMR inconclusive stress test referred for vasodilator stress perfusion CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction. CMR-related coronary revascularization was defined as any revascularisation occurring within 90 days after CMR. Univariable and multivariable Cox regressions were performed to determine the prognostic value of each parameter. Results Of 1563 patients who completed the CMR protocol, 1402 patients (66.7% male, 69.5 ± 11.0 years) completed the follow-up (median [interquartile range], 6.5 [5.6–7.5] years); 197 experienced a MACE (14.1%). Vasodilator stress CMR was well tolerated without severe adverse events. Using Kaplan–Meier analysis, inducible ischemia and late gadolinium enhancement (LGE) were significantly associated with the occurrence of MACE (hazard ratio, HR: 2.88 [95% CI 2.18–3.81]; and HR: 1.46 [95% CI 1.16–1.89], both p < 0.001; respectively). In multivariable Cox regression, the presence and extent of inducible ischemia were independent predictors of a higher incidence of MACE (HR: 2.53 [95% CI 1.89–3.40]; and HR: 1.58 [95% CI 1.47–1.71]; both p < 0.001; respectively). After adjustment, the extent of inducible ischemia showed the best improvement in model discrimination above traditional risk factors (C-statistic 0.75 [95% CI 0.69–0.81] with C-statistic improvement: 0.12). The study suggested no benefit of CMR-related coronary revascularization in reducing MACE. Conclusions In patients with a first non-CMR inconclusive stress test, vasodilator stress CMR has good prognostic value to predict MACE offering an incremental prognostic value over traditional risk factors.

Stress cardiovascular magnetic resonance and mortality in a registry of 2496 elderly patients with chronic coronary syndrome. Prognosis and decision-making

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER) Introduction and objectives. Management of the elderly with chronic coronary syndrome (CCS) is challenging. We explore the prognostic value and the usefulness for decision-making of the ischemic burden determined by vasodilator stress cardiac magnetic resonance (CMR) imaging in elderly patients with known or suspected CCS. Methods. The study group was made up of 2496 patients older than 70 years submitted to vasodilator stress CMR for known or suspected CCS. The ischemic burden (number of segments with stress-induced perfusion deficit) was calculated following the 17-segment model. Its association with all-cause mortality and the effect of CMR-guided revascularization were analyzed retrospectively. Results. During a median follow-up of 4.58 years, 430 deaths (17.2%) were recorded. A larger ischemic burden was an independent predictor of mortality: hazard ratio [95% confidence intervals]: 1.04 [1.01-1.07] for each additional ischemic segment, p = 0.006). This association also occurred in patients over 80 years of age and in women (p &lt; 0.001). Compared to non-revascularized patients, revascularization associated with worse outcomes at low ischemic burden and exerted protective prognostic effect in patients with extensive ischemia both in the whole group (p for interaction = 0.003) and in 496 patients matched 1:1 by a propensity score (p = 0.06). Conclusions. Vasodilator stress CMR represents a valuable tool to stratify risk in elderly patients with CCS and might be helpful to guide decision-making in this scenario.

Sex differences in mortality in stable patients undergoing vasodilator stress cardiovascular magnetic resonance

ObjectiveWe assessed the influence of the ischaemic burden (IB) as derived from vasodilator stress cardiovascular magnetic resonance (CMR) on the risk of death and the effect of revascularisation across sex.MethodsWe evaluated 6237 consecutive patients with known or suspected chronic coronary syndrome (CCS). Extensive ischaemia was defined as >5 segments with perfusion deficit. Multivariate Cox proportional hazard regression models were used.ResultsA total of 2371 (38.0%) patients were women and 583 (9.3%) underwent CMR-related revascularisation. During a median follow-up of 5.13 years, 687 (11.0%) deaths were reported. We found an adjusted differential effect of CMR-derived IB across sex (p value for interaction=0.039). Women exhibited an adjusted lower risk of death and only equaled men’s risk when extensive ischaemia was present. Likewise, CMR-related revascularisation was shown to be differentially associated with the risk of mortality across sex (p value for interaction=0.025). In patients with non-extensive ischaemia, revascularisation was associated with a higher risk of death, with a greater extent in women. At higher IB, revascularisation was associated with a lower risk in men, with more uncertain results in women.ConclusionsCMR-derived IB allows predicting the risk of death and gives insight into the potential effect of revascularisation in men and women with CCS. Compared with men, women with non-extensive ischaemia displayed a lower risk and a similar risk with a higher IB. The impact of CMR-related revascularisation on mortality risk was also significantly different according to IB and sex. Further research will be needed to confirm these hypothesis-generating findings.