Ischemia with no obstructive coronary artery disease (INOCA) is prevalent in women and is associated with increased risk of developing heart failure with preserved ejection fraction (HFpEF); however, ...the mechanism(s) contributing to this progression remains unclear. Given that diastolic dysfunction is common in women with INOCA, defining mechanisms related to diastolic dysfunction in INOCA could identify therapeutic targets to prevent HFpEF.
Cardiac MRI was performed in 65 women with INOCA and 12 reference controls. Diastolic function was defined by left ventricular early diastolic circumferential strain rate (eCSRd). Contributors to diastolic dysfunction were chosen a priori as coronary vascular dysfunction (myocardial perfusion reserve index MPRI), diffuse myocardial fibrosis (extracellular volume ECV), and aortic stiffness (aortic pulse wave velocity aPWV).
Compared to controls, eCSRd was lower in INOCA (1.61 ± 0.33/s vs. 1.36 ± 0.31/s, P = 0.016); however, this difference was not exaggerated when the INOCA group was sub-divided by low and high MPRI (P > 0.05) nor was ECV elevated in INOCA (29.0 ± 1.9% vs. 28.0 ± 3.2%, control vs. INOCA; P = 0.38). However, aPWV was higher in INOCA vs. controls (8.1 ± 3.2 m/s vs. 6.1 ± 1.5 m/s; P = 0.045), and was associated with eCSRd (r = −0.50, P < 0.001). By multivariable linear regression analysis, aPWV was an independent predictor of decreased eCSRd (standardized β = −0.39, P = 0.003), as was having an elevated left ventricular mass index (standardized β = −0.25, P = 0.024) and lower ECV (standardized β = 0.30, P = 0.003).
These data provide mechanistic insight into diastolic dysfunction in women with INOCA, identifying aortic stiffness and ventricular remodeling as putative therapeutic targets.
•INOCA is prevalent in women and is associated with increased risk of developing HFpEF.•The mechanism(s) contributing to heart failure progression in women with INOCA remains unclear.•Here we show that elevated aotric stiffness is an independent predictor of impaired diastolic function in INOCA.
Abstract
Aims
Ischaemia on single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is strongly associated with cardiovascular risk. Transient ischaemic dilation (TID) ...and post-stress wall motion abnormalities (WMA) are non-perfusion markers of ischaemia with incremental prognostic utility. Using a large, multicentre SPECT MPI registry, we assessed the degree to which these features increased the risk of major adverse cardiovascular events (MACE) in patients with less than moderate ischaemia.
Methods and results
Ischaemia was quantified with total perfusion deficit using semiautomated software and classified as: none (<1%), minimal (1 to <5%), mild (5 to <10%), moderate (10 to <15%), and severe (≥15%). Univariable and multivariable Cox proportional hazard analyses were used to assess associations between high-risk imaging features and MACE. We included 16 578 patients, mean age 64.2 and median follow-up 4.7 years. During follow-up, 1842 patients experienced at least one event. Patients with mild ischaemia and TID were more likely to experience MACE compared with patients without TID adjusted hazard ratio (HR) 1.42, P = 0.023, with outcomes not significantly different from patients with moderate ischaemia without other high-risk features (unadjusted HR 1.15, P = 0.556). There were similar findings in patients with post-stress WMA. However, in multivariable analysis of patients with mild ischaemia, TID (adjusted HR 1.50, P = 0.037), but not WMA, was independently associated with increased MACE.
Conclusion
In patients with mild ischaemia, TID or post-stress WMA identify groups of patients with outcomes similar to patients with moderate ischaemia. Whether these combinations identify patients who may derive benefit from revascularization deserves further investigation.
Semiquantitative assessment of stress myocardial perfusion defect has been shown to have greater prognostic value for prediction of major adverse cardiac events (MACE) in women compared with men in ...single-center studies with conventional single-photon emission computed tomography (SPECT) cameras. We evaluated sex-specific difference in the prognostic value of automated quantification of ischemic total perfusion defect (ITPD) and the interaction between sex and ITPD using high-efficiency SPECT cameras with solid-state detectors in an international multicenter imaging registry (REFINE SPECT Registry of Fast Myocardial Perfusion Imaging With Next-Generation SPECT).
Rest and exercise or pharmacological stress SPECT myocardial perfusion imaging were performed in 17 833 patients from 5 centers. MACE was defined as the first occurrence of death or myocardial infarction. Total perfusion defect (TPD) at rest, stress, and ejection fraction were quantified automatically by software. ITPD was given by stressTPD-restTPD. Cox proportional hazards model was used to evaluate the association between ITPD versus MACE-free survival and expressed as a hazard ratio.
In 10614 men and 7219 women, with a median follow-up of 4.75 years (interquartile range, 3.7-6.1), there were 1709 MACE. In a multivariable Cox model, after adjusting for revascularization and other confounding variables, ITPD was associated with MACE (hazard ratio, 1.08 95% CI, 1.05-1.1;
<0.001). There was an interaction between ITPD and sex (
<0.001); predicted survival for ITPD<5% was worse among men compared to women, whereas survival among women was worse than men for ITPD≥5%,
<0.001.
In the international, multicenter REFINE SPECT registry, moderate and severe ischemia as quantified by ITPD from high-efficiency SPECT is associated with a worse prognosis in women compared with men.
Abstract Objective We explored whether the presence of 3 known features of plaque vulnerability on coronary CT angiography (CCTA) – low attenuation plaque content (LAP), positive remodeling (PR), and ...spotty calcification (SC) – identifies plaques associated with greater inducible myocardial hypoperfusion measured by myocardial perfusion imaging (MPI). Methods We analyzed 49 patients free of cardiac disease who underwent CCTA and MPI within a 6-month period and were found on CCTA to have focal 70–99% stenosis from predominantly non-calcified plaque in the proximal or mid segment of 1 major coronary artery. Presence of LAP (≤30 Hounsfield Units), PR (outer wall diameter exceeds proximal reference by ≥5%), and SC (≤3 mm long and occupies ≤90° of cross-sectional artery circumference) was determined. On MPI, reversible hypoperfusion in the myocardial territory corresponding to the diseased artery was quantified both as percentage of total myocardium (RevTPDART ) by an automatic algorithm and as summed difference score (SDSART ) by two experienced readers. RevTPDART ≥ 3% and SDSART ≥ 3 defined significant inducible hypoperfusion in the territory of the diseased artery. Results Plaques in patients with RevTPDART ≥ 3% more frequently exhibited LAP (70% vs. 14%, p < 0.001) and PR (70% vs. 24%, p = 0.001) but not SC (55% vs. 34%, p = 0.154). RevTPDART increased from 1.3 ± 1.2% in arteries with LAP−/PR− plaques to 3.2 ± 4.3% with LAP+/PR− or LAP−/PR+ plaques to 8.3 ± 2.4% with LAP+/PR+ plaques ( p < 0.001); SDSART showed a similar increase: 0.3 ± 0.7 to 2.3 ± 2.8 to 6.0 ± 3.8 ( p < 0.001). Using the same LAP/PR categorization, there was a marked increase in the frequency of significant hypoperfusion as determined by both RevTPDART ≥ 3% (1/19 to 10/21 to 9/9, p < 0.001) and SDSART ≥ 3 (1/19 to 8/21 to 8/9, p < 0.001). LAP and PR, but not SC, were strong predictors of RevTPDART and SDSART in regression models adjusting for potential confounders. Conclusions Presence of low attenuation plaque and positive remodeling in severely stenotic plaques on CCTA is strongly predictive of myocardial hypoperfusion and may be useful in assessing the hemodynamic significance of such lesions.
This study sought to evaluate the incremental value of quantifying the extent and severity of myocardial perfusion and 18F-labeled fluorodeoxyglucose (FDG) abnormalities in predicting adverse ...outcomes among patients with suspicion for cardiac sarcoidosis (CS).
Positron emission tomography (PET) with FDG is a key component of the noninvasive assessment of patients with suspected CS. However, the optimal method for image interpretation has not been defined.
A retrospective analysis was performed of 203 patients who underwent perfusion and FDG-PET imaging to evaluate for CS. Imaging findings were scored by conventional 3-category methods (normal perfusion and metabolism, abnormal perfusion or metabolism, abnormal perfusion and metabolism) and by summed scores using the 17-segment model to represent extent and severity of disease. Heterogeneity of metabolism was quantified using the coefficient of variation (SD divided by the mean) of FDG uptake. Multivariable Cox models were developed to assess associations between imaging findings and adverse events (death, heart transplant, or ventricular arrhythmia requiring defibrillation).
The indication for FDG-PET was ventricular arrhythmia in 69 (34%), heart block in 16 (8%), cardiomyopathy in 54 (27%), and other indications in 64 (32%). There were 63 patients who developed adverse events over a mean follow-up of 1.8 years. After robust adjustment, only the summed score in segments with a perfusion–metabolism mismatch and the coefficient of variation were important prognostically (p = 0.029 and p = 0.041, respectively).
Quantitative measures of extent and severity of perfusion–metabolism mismatch and coefficient of variation of FDG uptake provide an incremental prognostic advantage in patients undergoing FDG-PET for CS. These results support the use of a more detailed analysis of imaging findings, as is conventional in coronary artery disease.
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Patients with locally advanced non-small cell lung cancer (LA-NSCLC) have a high prevalence of pre-existing coronary heart disease and face excess cardiac risk after thoracic radiation therapy. We ...sought to assess whether statin therapy is a predictor of overall survival (OS) after thoracic radiation therapy.
We performed a retrospective analysis of 748 patients with LA-NSCLC treated with thoracic radiation therapy, using Kaplan-Meier OS estimates and Cox regression.
Statin use among high cardiac risk patients (Framingham risk ≥20% or pre-existing coronary heart disease; n = 496) was 51.2%. After adjustment for baseline cardiac risk and other prognostic factors, statin therapy was associated with a significantly increased risk of all-cause mortality (adjusted hazard ratio, 1.39; 95% confidence interval CI, 1.00-1.91; P = .048) but not major adverse cardiac events (adjusted hazard ratio, 1.18; 95% CI, 0.52-2.68; P = .69). Among statin-naïve patients, mean heart dose ≥10 Gy versus <10 Gy was associated with a significantly increased risk of all-cause mortality (hazard ratio, 1.32; 95% CI, 1.04-1.68; P = .022), with 2-year OS estimates of 46.9% versus 60.0%, respectively. However, OS did not differ by heart dose among patients on statin therapy (hazard ratio, 1.00; 95% CI, 0.76-1.32; P = 1.00; P-interaction = .031), with 2-year OS estimates of 46.9% versus 50.3%, respectively.
Among patients with LA-NSCLC, only half of statin-eligible high cardiac risk patients were on statin therapy, reflecting the highest cardiac risk level of our cohort. Statin use was an independent predictor of all-cause mortality but not major adverse cardiac events. Elevated mean heart dose (≥10 Gy) was associated with increased risk of all-cause mortality in statin-naïve patients but not among those on statin therapy, identifying a group of patients in which early intervention with statins may mitigate the deleterious effects of high heart radiation therapy dose. This warrants evaluation in prospective trials.
It has been shown that CT attenuation of noncalcified plaques depends on luminal contrast attenuation (LCA). Although tube potential (kilovolt kV) has been shown to exert influence on plaque ...attenuation through LCA as well as its direct effects, in-vivo studies have not investigated plaque attenuation at lower tube potentials less than 120 kV. We sought to evaluate the effect of kV and LCA on thresholds for lipid-rich and fibrous plaques as defined by intravascular ultrasound (IVUS).
CT attenuation of IVUS-defined plaque components (lipid-rich, fibrous, and calcified plaques) were quantified in 52 consecutive patients with unstable angina, who had coronary CT angiography performed at 100 kV (n = 25) or 120 kV (n = 27) using kV-adjusted contrast protocol prior to IVUS. CT attenuation of plaque components was compared between the two groups.
LCA was similar in the 100-kV and 120-kV groups (417.6 ± 83.7 Hounsfield Units HU vs 421.3 ± 54.9 HU, p = 0.77). LCA correlated with CT attenuation of lipid-rich (r = 0.49, p = 0.001) and fibrous plaques (r = 0.32, p < 0.05), but not with that of calcified plaques (r = 0.04, p = 0.81). When plaque attenuation was normalized to LCA, lipid-rich (0.087 ± 0.036, range −0.012–0.147) and fibrous plaque attenuation (0.234 ± 0.056, range 0.153–0.394) were distinct (p < 0.001) with no overlap for both kV groups. CT attenuation was not significantly different between 100-kV and 120-kV groups for lipid-rich (34.0 ± 21.5 vs 39.3 ± 12.9, p = 0.33) or fibrous plaques (95.4 ± 19.1 vs 97.6 ± 22.0, p = 0.75).
Plaque attenuation thresholds for non-calcified plaque components should be adjusted based on LCA. Further adjustment may not be required for different tube potentials.
Phase analysis of single-photon emission computed tomography myocardial perfusion imaging provides dyssynchrony information which correlates well with assessments by echocardiography, but the ...independent prognostic significance is not well defined. This study assessed the independent prognostic value of single-photon emission computed tomography-myocardial perfusion imaging phase analysis in the largest multinational registry to date across all modalities.
From the REFINE SPECT (Registry of Fast Myocardial Perfusion Imaging With Next Generation SPECT), a total of 19 210 patients were included (mean age 63.8±12.0 years and 56% males). Poststress total perfusion deficit, left ventricular ejection fraction, and phase variables (phase entropy, bandwidth, and SD) were obtained automatically. Cox proportional hazards analyses were performed to assess associations with major adverse cardiac events (MACE).
During a follow-up of 4.5±1.7 years, 2673 (13.9%) patients experienced MACE. Annualized MACE rates increased with phase variables and were ≈4-fold higher between the second and highest decile group for entropy (1.7% versus 6.7%). Optimal phase variable cutoff values stratified MACE risk in patients with normal and abnormal total perfusion deficit and left ventricular ejection fraction. Only entropy was independently associated with MACE. The addition of phase entropy significantly improved the discriminatory power for MACE prediction when added to the model with total perfusion deficit and left ventricular ejection fraction (
<0.0001).
In a largest to date imaging study, widely representative, international cohort, phase variables were independently associated with MACE and improved risk stratification for MACE beyond the prediction by perfusion and left ventricular ejection fraction assessment alone. Phase analysis can be obtained fully automatically, without additional radiation exposure or cost to improve MACE risk prediction and, therefore, should be routinely reported for single-photon emission computed tomography-myocardial perfusion imaging studies.
Background
Echocardiography plays an important role in the diagnostic work up of heart failure with preserved ejection fraction (HFpEF). We sought to determine the left ventricular (LV) diastolic ...profile by echocardiography in patients diagnosed with pulmonary hypertension (PH) due to PH‐HFpEF.
Hypothesis
The study of LV diastolic function by echocardiography has limitations in patients with HFpEF and PH, and certain LV diastolic determinations convey a worse prognosis.
Methods
We included patients with postcapillary PH and diagnosis of PH‐HFpEF. Investigators reviewed Doppler echocardiograms completed within 3 months of the diagnostic right heart catheterization.
Results
We included 149 patients with a mean ± standard deviation age of 63 ± 14 years; 58% were women. LV diastolic function profile was determined as normal (41%), grade I (34%), and grade II and grade III (25%). Pulmonary artery pressure and pulmonary vascular resistance were higher and cardiac output lower in patients with LV diastolic dysfunction profile; however, pulmonary artery wedge pressure was not significantly different among grades of LV diastolic function. Although there was an association between the presence of LV diastolic dysfunction profile and long‐term survival (P = 0.03), it disappeared when adjusting for age and gender. Right ventricular (RV) dysfunction, paradoxical septal motion, and higher RV systolic pressure remained the only variables significantly associated with poor survival.
Conclusions
The profile of LV diastolic dysfunction by conventional echocardiography is highly variable in patients with PH‐HFpEF and has no significant impact on long‐term survival. A more severe RV function and higher right ventricle systolic pressure were associated with worse survival.
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