Coronary Wave Intensity Analysis as an Invasive and Vessel-Specific Index of Myocardial Viability.

BACKGROUND: Coronary angiography and viability testing are the cornerstones of diagnosing and managing ischemic cardiomyopathy. At present, no single test serves both needs. Coronary wave intensity analysis interrogates both contractility and microvascular physiology of the subtended myocardium and therefore has the potential to fulfil the goal of completely assessing coronary physiology and myocardial viability in a single procedure. We hypothesized that coronary wave intensity analysis measured during coronary angiography would predict viability with a similar accuracy to late-gadolinium-enhanced cardiac magnetic resonance imaging. METHODS: Patients with a left ventricular ejection fraction ≤40% and extensive coronary disease were enrolled. Coronary wave intensity analysis was assessed during cardiac catheterization at rest, during adenosine-induced hyperemia, and during low-dose dobutamine stress using a dual pressure-Doppler sensing coronary guidewire. Scar burden was assessed with cardiac magnetic resonance imaging. Regional left ventricular function was assessed at baseline and 6-month follow-up after optimization of medical-therapy±revascularization, using transthoracic echocardiography. The primary outcome was myocardial viability, determined by the retrospective observation of functional recovery. RESULTS: Forty participants underwent baseline physiology, cardiac magnetic resonance imaging, and echocardiography, and 30 had echocardiography at 6 months; 21/42 territories were viable on follow-up echocardiography. Resting backward compression wave energy was significantly greater in viable than in nonviable territories (-5240±3772 versus -1873±1605 W m-2 s-1, P<0.001), and had comparable accuracy to cardiac magnetic resonance imaging for predicting viability (area under the curve 0.812 versus 0.757, P=0.649); a threshold of -2500 W m-2 s-1 had 86% sensitivity and 76% specificity. CONCLUSIONS: Backward compression wave energy has accuracy similar to that of late-gadolinium-enhanced cardiac magnetic resonance imaging in the prediction of viability. Coronary wave intensity analysis has the potential to streamline the management of ischemic cardiomyopathy, in a manner analogous to the effect of fractional flow reserve on the management of stable angina.

Power Modulation Echocardiography to Detect and Quantify Myocardial Scar.

BACKGROUND: Myocardial scar correlates with clinical outcomes. Traditionally, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is used to detect and quantify scar. In this prospective study using LGE CMR as reference, the authors hypothesized that nonlinear ultrasound imaging, namely, power modulation, can detect and quantify myocardial scar in selected patients with previous myocardial infarction. In addition, given the different histopathology between ischemic and nonischemic scar, a further aim was to test the diagnostic performance of this echocardiographic technique in unselected consecutive individuals with ischemic and nonischemic LGE or no LGE on CMR. METHODS: Seventy-one patients with previous myocardial infarction underwent power modulation echocardiography following CMR imaging (group A). Subsequently, 101 consecutive patients with or without LGE on CMR, including individuals with nonischemic LGE, were scanned using power modulation echocardiography (group B). RESULTS: In group A, echocardiography detected myocardial scar in all 71 patients, with good scar volume agreement with CMR (bias = -1.9 cm3; limits of agreement [LOA], -8.0 to 4.2 cm3). On a per-segment basis, sensitivity was 82%, specificity 97%, and accuracy 92%. Sensitivity was higher in the inferior and posterior segments and lower in the anterior and lateral walls. In group B, on a per-subject basis, the sensitivity of echocardiography was 62% (91% for ischemic and 30% for nonischemic LGE), with specificity and accuracy of 89% and 72%, respectively. The bias for scar volume between modalities was 5.9 cm3, with LOA of 34.6 to 22.9 cm3 (bias = -1.9 cm3 [LOA, -11.4 to 7.6 cm3] for ischemic LGE, and bias = 18.9 cm3 [LOA, -67.4 to 29.7.6 cm3] for nonischemic LGE). CONCLUSIONS: Power modulation echocardiography can detect myocardial scar in both selected and unselected individuals with previous myocardial infarction and has good agreement for scar volume quantification with CMR. In an unselected cohort with nonischemic LGE, sensitivity is low.

Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans.

AIMS: Neuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles in brain blood flow regulation while dysfunctional nNOS signalling is implicated in cerebrovascular ischaemia and migraine. Previous human studies have investigated the effects of non-selective NOS inhibition but there has been no direct investigation of the role of nNOS in human cerebrovascular regulation. We hypothesized that inhibition of the tonic effects of nNOS would result in global or localized changes in cerebral blood flow (CBF), as well as changes in functional brain connectivity. METHODS AND RESULTS: We investigated the acute effects of a selective nNOS inhibitor, S-methyl-L-thiocitrulline (SMTC), on CBF and brain functional connectivity in healthy human volunteers (n = 19). We performed a randomized, placebo-controlled, crossover study with either intravenous SMTC or placebo, using magnetic resonance imaging protocols with arterial spin labelling and functional resting state neuroimaging. SMTC infusion induced an ∼4% decrease in resting global CBF [-2.3 (-0.3, -4.2) mL/100g/min, mean (95% confidence interval, CI), P = 0.02]. In a whole-brain voxel-wise factorial-design comparison of CBF maps, we identified a localized decrease in regional blood flow in the right hippocampus and parahippocampal gyrus following SMTC vs. placebo (2921 voxels; T = 7.0; x = 36; y = -32; z = -12; P < 0.001). This was accompanied by a decrease in functional connectivity to the left superior parietal lobule vs. placebo (484 voxels; T = 5.02; x = -14; y = -56; z = 74; P = 0.009). These analyses adjusted for the modest changes in mean arterial blood pressure induced by SMTC as compared to placebo [+8.7 mmHg (+1.8, +15.6), mean (95% CI), P = 0.009]. CONCLUSIONS: These data suggest a fundamental physiological role of nNOS in regulating regional CBF and functional connectivity in the human hippocampus. Our findings have relevance to the role of nNOS in the regulation of cerebral perfusion in health and disease.

The Impact of Vendor-Specific Ultrasound Beam-Forming and Processing Techniques on the Visualization of In Vitro Experimental "Scar": Implications for Myocardial Scar Imaging Using Two-Dimensional and Three-Dimensional Echocardiography.

BACKGROUND: Myocardial scar appears brighter compared with normal myocardium on echocardiography because of differences in tissue characteristics. The aim of this study was to test how different ultrasound pulse characteristics affect the brightness contrast (i.e., contrast ratio [CR]) between tissues of different acoustic properties, as well as the accuracy of assessing tissue volume. METHODS: An experimental in vitro "scar" model was created using overheated and raw pieces of commercially available bovine muscle. Two-dimensional and three-dimensional ultrasound scanning of the model was performed using combinations of ultrasound pulse characteristics: ultrasound frequency, harmonics, pulse amplitude, steady pulse (SP) emission, power modulation (PM), and pulse inversion modalities. RESULTS: On both two-dimensional and three-dimensional imaging, the CR between the "scar" and its adjacent tissue was higher when PM was used. PM, as well as SP ultrasound imaging, provided good "scar" volume quantification. When tested on 10 "scars" of different size and shape, PM resulted in lower bias (-9.7 vs 54.2 mm3) and narrower limits of agreement (-168.6 to 149.2 mm3 vs -296.0 to 404.4 mm3, P = .03). The interobserver variability for "scar" volume was better with PM (intraclass correlation coefficient = 0.901 vs 0.815). Two-dimensional and three-dimensional echocardiography with PM and SP was performed on 15 individuals with myocardial scar secondary to infarction. The CR was higher on PM imaging. Using cardiac magnetic resonance as a reference, quantification of myocardial scar volume showed better agreement when PM was used (bias, -645 mm3; limits of agreement, -3,158 to 1,868 mm3) as opposed to SP (bias, -1,138 mm3; limits of agreement, -5,510 to 3,233 mm3). CONCLUSIONS: The PM modality increased the CR between tissues with different acoustic properties in an experimental in vitro "scar" model while allowing accurate quantification of "scar" volume. By applying the in vitro findings to humans, PM resulted in higher CR between scarred and healthy myocardium, providing better scar volume quantification than SP compared with cardiac magnetic resonance.

Direct cardiac versus systemic effects of inorganic nitrite on human left ventricular function.

Inorganic nitrite is a source of nitric oxide (NO) and is considered as a potential therapy in settings where endogenous NO bioactivity is reduced and left ventricular (LV) function impaired. However, the effects of nitrite on human cardiac contractile function, and the extent to which these are direct or indirect, are unclear. We studied 40 patients undergoing diagnostic cardiac catheterization who had normal LV systolic function and were not found to have obstructive coronary disease. They received either an intracoronary sodium nitrite infusion (8.7-26 µmol/min, n = 20) or an intravenous sodium nitrite infusion (50 µg/kg/min, n = 20). LV pressure-volume relations were recorded. The primary end point was LV end-diastolic pressure (LVEDP). Secondary end points included indices of LV systolic and diastolic function. Intracoronary nitrite infusion induced a significant reduction in LVEDP, LV end-diastolic pressure-volume relationship (EDPVR), and the time to LV end-systole (LVEST) but had no significant effect on LV systolic function or systemic hemodynamics. Intravenous nitrite infusion induced greater effects, with significant decreases in LVEDP, EDPVR, LVEST, LV dP/dtmin, tau, and mean arterial pressure. Inorganic nitrite has modest direct effects on human LV diastolic function, independent of LV loading conditions and without affecting LV systolic properties. However, the systemic administration of nitrite has larger effects on LV diastolic function, which are related to reduction in both preload and afterload. These contractile effects of inorganic nitrite may indicate a favorable profile for conditions characterized by LV diastolic dysfunction.NEW & NOTEWORTHY This is the first study to assess the direct and indirect effects of inorganic nitrite on invasive measures of left ventricular function in humans in vivo. Inorganic nitrite has a modest direct myocardial effect, improving diastolic function. Systemic administration of nitrite has larger effects related to alterations in cardiac preload and afterload. The changes induced by nitrite appear favorable for potential use in conditions characterized by LV diastolic dysfunction.

Predictive model of increased mortality and bed occupancy if thrombolysis becomes the initial treatment strategy for STEMI during the SARS-CoV-2 pandemic.

During the current SARS-CoV-2 pandemic the restructure of healthcare services to meet the huge increase in demand for hospital resource and capacity has led to the proposal that where necessary ST elevation myocardial infarction (STEMI) could be managed by intravenous thrombolysis in the first instance as a means of reducing the workforce requirements of a primary angioplasty service run at a heart attack centre. Our modelling, based on data from the UK, shows that contrary to reducing demand, the effect on both mortality and bed occupancy would be negative with 158 additional deaths per year for each 10% reduction in primary angioplasty and at a cost of ~8,000 additional bed days per year for the same reduction. Our analysis demonstrates that specialist services such as heart attack pathways should be protected during the COVID crisis to maximise the appropriate use of resource and prevent unnecessary mortality.

Therapies to limit myocardial injury in animal models of myocarditis: a systematic review and meta-analysis.

Current myocarditis guidelines do not advocate treatment to prevent myocardial injury and scar deposition in patients with myocarditis and normal left ventricular ejection fraction. We aimed to ascertain the utility of beta blockers, calcium channel blockers and antagonists of the renin-angiotensin system in ameliorating myocardial injury, scar formation and calcification in animal in vivo models of myocarditis. The project was prospectively registered with the PROSPERO database of systematic reviews (CRD42018089336). Primary outcomes (necrosis, fibrosis and calcification) were meta-analysed with random-effects modelling. 52 studies were systematically reviewed. Meta-analysis was performed compared with untreated controls. In each study, we identified all independent comparisons of treatment versus control groups. The pooled weighted mean difference (WMD) indicated treatment reduced necrosis by 16.9% (71 controlled analyses, 95% CI 13.2-20.7%; P < 0.001), however there was less evidence of an effect after accounting for publication bias. Treatment led to a 12.8% reduction in fibrosis (73 controlled analyses, 95% CI 7.6-18.0%; P < 0.001). After accounting for publication bias this was attenuated to 7.8% but remained significant. Treatment reduced calcification by 4.1% (28 controlled analyses, 95% CI 0.2-8.0%; P < 0.0395). We observed significant heterogeneity in effect size in all primary endpoints, which was predominantly driven by differences between drug categories. Beta blockers and angiotensin-converting enzyme (ACE) inhibitors were the only agents that were effective for both necrosis and fibrosis, while only ACE inhibitors had a significant effect on calcification. This study provides evidence for a role for ACE inhibitors and beta blockers to prevent myocardial injury and scar deposition in in vivo models of myocarditis. There is a need for further well-designed studies to assess the translational application of these treatments.

Phaeochromocytoma found on cardiovascular magnetic resonance in a patient presenting with acute myocarditis: an unusual association.

Myocarditis is inflammation of the cardiac muscle. The symptoms, signs and basic investigation findings can mimic that of myocardial infarction. The most common cause is infection (most commonly viral). Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive diagnostic test for potential acute myocarditis as it allows assessment of myocardial oedema and scar. A man aged 25 years was admitted with chest pain, dizziness, headache, palpitations and sweating. His troponin was mildly positive. A CMR was performed which showed mild myocarditis and a right suprarenal mass which was confirmed to be a phaeochromocytoma based on biochemistry and a dedicated imaging workup. Phaeochromocytoma can lead to cardiac involvement in the form of left ventricular dysfunction, or catecholamine-induced myocarditis.

Clinical applications of multiparametric CMR in left ventricular hypertrophy.

There are a number of diseases which can increase left ventricular myocardial wall thickness through a number of different mechanisms. Multi-parametric mapping techniques are a new addition to the cardiovascular magnetic resonance (CMR) armoury with a number of potential clinical roles. In this review article, we will explore the role of imaging in left ventricular hypertrophy, and particularly developments in CMR. We focus on ability of CMR to characterize myocardial tissue using multiparametric mapping (native T1, T2 and extracellular volume mapping), to bridge from the microscopic histological domain and into the clinical domain of non-invasive imaging.

Prognostic Value of Quantitative Stress Perfusion Cardiac Magnetic Resonance.

OBJECTIVES: This study sought to evaluate the prognostic usefulness of visual and quantitative perfusion cardiac magnetic resonance (CMR) ischemic burden in an unselected group of patients and to assess the validity of consensus-based ischemic burden thresholds extrapolated from nuclear studies. BACKGROUND: There are limited data on the prognostic value of assessing myocardial ischemic burden by CMR, and there are none using quantitative perfusion analysis. METHODS: Patients with suspected coronary artery disease referred for adenosine-stress perfusion CMR were included (n = 395; 70% male; age 58 ± 13 years). The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, aborted sudden death, and revascularization after 90 days. Perfusion scans were assessed visually and with quantitative analysis. Cross-validated Cox regression analysis and net reclassification improvement were used to assess the incremental prognostic value of visual or quantitative perfusion analysis over a baseline clinical model, initially as continuous covariates, then using accepted thresholds of ≥2 segments or ≥10% myocardium. RESULTS: After a median 460 days (interquartile range: 190 to 869 days) follow-up, 52 patients reached the primary endpoint. At 2 years, the addition of ischemic burden was found to increase prognostic value over a baseline model of age, sex, and late gadolinium enhancement (baseline model area under the curve [AUC]: 0.75; visual AUC: 0.84; quantitative AUC: 0.85). Dichotomized quantitative ischemic burden performed better than visual assessment (net reclassification improvement 0.043 vs. 0.003 against baseline model). CONCLUSIONS: This study was the first to address the prognostic benefit of quantitative analysis of perfusion CMR and to support the use of consensus-based ischemic burden thresholds by perfusion CMR for prognostic evaluation of patients with suspected coronary artery disease. Quantitative analysis provided incremental prognostic value to visual assessment and established risk factors, potentially representing an important step forward in the translation of quantitative CMR perfusion analysis to the clinical setting.

Rosai-Dorfman disease and the heart.

Rosai-Dorfman disease (RDD) is a non-malignant pathology of histiocyte proliferation. The classical clinical presentation is with painless cervical lymphadenopathy, but extranodal involvement is frequent, occurring in approximately 40% of cases. The literature was systematically reviewed to identify reported cases of RDD with cardiac involvement. Eighteen cases were identified (3 pediatric and 15 adult). In adult cardiac RDD (cRDD), three patterns of disease were noted: an intra-cardiac mass, epicardial involvement, and pulmonary artery involvement. Reported cases suggest that surgical excision of intra-cardiac masses confers a good prognosis.