Myocardial stress perfusion scintigraphy for outcome prediction in patients with severe left ventricular systolic dysfunction.

Coronary angiography has been recommended in all patients with suspected chronic coronary syndrome and left ventricular ejection fraction (LVEF) ≤35%. The role of ischemia testing, for example, through stress-rest myocardial perfusion scintigraphy (MPS), for risk prediction is not well established. METHODS: We evaluated 1576 consecutive patients referred to MPS and stratified into 3 LV ejection fraction (LVEF) categories: ≤35%, 36-49%, and ≥ 50%. RESULTS: Patients with LVEF ≤35% were oldest, most often men, and with the highest likelihood of prior early (elective or urgent) coronary revascularization. They had also the highest values or summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS), as well as the highest frequency of significant coronary artery disease, and a greater number of diseased vessels. FOLLOW-UP: In this subgroup, 32 cardiovascular death or non-fatal myocardial infarction (MI) (21%), 35 all-cause deaths (22%), and 37 cardiovascular deaths, non-fatal MI, or late revascularizations (27%) were recorded with the shortest survival among all LVEF classes. SRS, SSS, and SDS had very low area under the curve values for the prediction of the 3 endpoints, with very high cut-offs, respectively. SRS and SSS cut-offs predicted a worse outcome in Cox regression models including the number of diseased vessels and early revascularization. CONCLUSIONS: In patients with LVEF ≤35%, SRS and SSS are less predictive of outcome than in patients with better preserved systolic dysfunction, but their cut-offs retain independent prognostic significance from the number of vessels with significant stenoses and from early revascularization.

Changes in left ventricle myocardial volume during stress test using cadmium-zinc-telluride cardiac imaging: Implications in coronary artery disease.

BACKGROUND: Cadmium-zinc-telluride (CZT) SPECT allows the estimation of left ventricle myocardial volume (LVMV). We tested the clinical relevance of rest-stress LVMV changes (Δ LVMV) in detecting coronary artery disease (CAD, coronary stenosis > 70%), using CZT-SPECT. METHODS: We prospectively enrolled 512 consecutive patients with known or suspected CAD (mean age: 70.3 ± 9.2 years, 72% male) for stress-rest myocardial perfusion imaging (MPI, single-day stress-rest protocol). We quantified summed stress scores (SSS), summed rest scores, and summed difference scores, together with LVMV and ejection fraction (EF) after stress and at rest. All patients underwent coronary angiography within 30 days. RESULTS: Two hundred seventy-two patients had CAD at coronary angiography. ΔLVMV ≤ 5 mL, corresponding to 6% of change from rest LVMV, was the best predictor of CAD (AUC = 0.831, 79% sensitivity, 82% specificity), irrespective of the stress protocol (dipyridamole or exercise stress) and independently of MPI-SSS, LV EF, and clinical history (P = 0.004). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were significant for the addition of ΔLVMV ≤ 5 mL (IDI = 6.1%, P < 0.0001; NRI = 29.7%, P = 0.02) to MPI-SSS, whereas the other parameters were not. CONCLUSIONS: The evaluation of ΔLVMV using CZT-SPECT can improve the diagnostic accuracy in predicting the presence of CAD when added to conventional MPI.

Relationships between left ventricular sympathetic innervation and diastolic dysfunction: the role of myocardial innervation/perfusion mismatch.

BACKGROUND: A possible relationship between cardiac sympathetic denervation and left ventricular (LV) diastolic dysfunction has been suggested. However, an evaluation of the interactions between myocardial adrenergic tone and LV perfusion and diastolic function is lacking. METHODS AND RESULTS: Seventy-two patients underwent 99mTc-tetrofosmin/123I-metaiodobenzylguanidine (123I-MIBG) cardiac Cadmium-Zinc-Telluride (CZT) imaging. The summed rest score (SRS) and summed 123I-MIBG score (SS-MIBG) were computed as measures of regional perfusion and innervation heterogeneities. LV segments showing an impaired innervation, despite a relatively preserved perfusion (99mTc-tetrofosmin-123I-MIBG tracers' uptake ≥25%), were individuated (innervation/perfusion mismatch). The peak filling rate (PFR) was computed as a measure of LV diastolic function. Nineteen of the 72 (26%) patients presented a normal LV diastolic function, while 29 (40%) and 24 (34%) had a mild and overt diastolic dysfunction. Subjects with diastolic dysfunction showed more abnormal SRS and SS-MIBG values (P < 0.001). In the global population, 502/1224 (41%) LV segments showed an innervation/perfusion mismatch. A modest correlation between the extent of cardiac innervation/perfusion mismatch and PFR values was evident (R = -0.27, P = 0.029). On multivariate analysis, the extent of regional innervation/perfusion mismatch remained an independent predictor of overt LV diastolic abnormalities (P = 0.017). CONCLUSIONS: The burden of LV regions showing an innervation/perfusion mismatch associates with the occurrence of overt diastolic dysfunction.

Influence of cardiac stress protocol on myocardial perfusion imaging accuracy: The role of exercise level on the evaluation of ischemic burden.

BACKGROUND: Some specifics of cardiac stress protocols, i.e., stressor used or exercise level achieved, may impact myocardial perfusion imaging (MPI) accuracy. METHODS: Four-hundred and seventy-five patients were submitted to MPI and coronary angiography. MPI was performed after exercise (303 patients) or dipyridamole stress (172 patients). A coronary stenosis ≥70% was considered significant. In case of exercise test, a peak heart rate (HR) <85% of the maximal age predicted was considered submaximal and categorized as follows: >75% and <85% ("Group 1"); <75% ("Group 2"). RESULTS: At coronary angiography, 312/475 (66%) patients showed significant stenosis. In the overall population, MPI showed a high accuracy in unmasking significant coronary stenosis, independently of the stress protocol adopted (AUC .76 for exercise vs .78 for vasodilator; P = NS). However, in case of an exercise stress test, a significant interaction between peak %HR and MPI diagnostic power was evident. While an elevated accuracy was still maintained in "Group 1" patients (AUC .79; P vs maximal exercise = NS), a significant drop was demonstrated in "Group 2" patients (AUC .66; P vs maximal exercise = .012, and P vs "Group 1" = .042). CONCLUSIONS: The accuracy of MPI is not influenced by the stress protocol adopted. Exercise MPI maintains an elevated accuracy as long as the %HR remains >75%.

T wave abnormalities identify patients with previous lateral wall myocardial infarction and circumflex artery disease.

BACKGROUND: The diagnosis of previous lateral myocardial infarction is based on QRS morphology. OBJECTIVES: To explore the diagnostic role of T wave abnormalities. METHODS: We studied 166 patients with known or suspected ischemic heart disease who underwent a 12-lead electrocardiogram, myocardial perfusion scintigraphy, and coronary arteriography within 90days. We excluded patients with bundle-branch block, hypertrophy, or paced rhythm. RESULTS: Only one patient had a prominent R wave in V1, no patient showed lateral Q waves of necrosis. T wave amplitude in V2-V6 ≥0.6mV, and T wave amplitude in lead 1+V6 ≤0mV detected a lateral infarction (sensitivity 33 and 44%, specificity 83 and 80%). T wave amplitude in lead 1+V6 ≤0mV was the only independent predictor of infarction or LCx occlusion (AUC 0.72 and 0.74). Serum potassium values were not associated with T wave abnormalities. CONCLUSION: T wave abnormalities identify previous lateral infarction and LCx disease.

Chronotropic response to vasodilator-stress in patients submitted to myocardial perfusion imaging: impact on the accuracy in detecting coronary stenosis.

AIMS: A lower heart rate response (HRR) during vasodilator MPI has been shown to have a relevant adverse prognostic impact. We sought to evaluate the interaction among individual HRR to vasodilator stress and myocardial perfusion imaging (MPI) accuracy in patients with suspected ischemic heart disease (IHD). METHODS AND RESULTS: One hundred and sixty-five consecutive patients were submitted to vasodilator-stress MPI on a cardiac camera equipped with cadmium-zinc-thelluride detectors and coronary angiography. A coronary stenosis >70 % was considered significant. In every patient, the summed difference score (SDS) was computed from MPI images. Patients were categorized according to the tertiles of the distribution of individual HRR during dipyridamole: "Group 1" (HRR < 8 bpm; lowest tertile); "Group 2" (8 ≤ HRR ≤ 12 bpm; middle tertile); "Group 3" (HRR >12 bpm; highest tertile). Significant coronary artery disease (CAD) was present in 102 (62 %) patients. In the overall population, MPI showed a significant accuracy (AUC: 0.81, 95 % CI 0.74-0.86; p < 0.001) in unmasking the presence of significant coronary stenosis. Interestingly, in patients with a blunted HRR during dipyridamole ("Group 1") MPI showed a significantly lower sensitivity (68 %) in detecting CAD than in those with a higher HRR ("Group 3") (91 %, p = 0.007), despite a preserved specificity (76 % vs 77 %, P=NS). Similarly, the correlation among CAD extent and post-stress LV functional stunning was limited to "Group 3" patients, while it disappeared in those with blunted HRR. CONCLUSIONS: In patients with suspected IHD, MPI sensitivity is strongly influenced by the magnitude of patient heart rate increase to the pharmacologic stressor, suggesting an interaction among blunted HRR and lower accuracy in unmasking CAD.

Myocardial bridging: a review with emphasis on electrocardiographic findings.

BACKGROUND: Myocardial bridging (MB) occurs when a segment of an epicardial coronary artery takes an intra- myocardial course, thus leading to systolic compression. Most myocardial bridges involve the left anterior descending artery and are observed in 14-35% of patients. Different pathophysiological mechanisms can induce symptoms secondary to myocardial ischemia: systolic coronary compression, diastolic dysfunction associated with aging and coronary atherosclerosis, LV hypertrophy, vasospasm, microvascular and endothelial dysfunction, plaque development proximal to the bridge. METHODS: We performed a literature review of MB, with a particular emphasis on electrocardiographic manifestations. RESULTS: Stable angina-like chest pain is the usual presentation and MB should be suspected in patients at low risk for coronary atherosclerosis which refer this symptom or which present myocardial ischemia at instrumental examinations. ECG changes are not specific for MB and resting ECG is often normal or presents ST segment anomalies. Exercise stress test often shows non specific signs of ischemia, conduction disturbances or arrhythmias which do not allow the distinction between myocardial bridging and other causes of myocardial ischemia; angina often appears during exercise, even in the absence of ECG changes. Myocardial perfusion deficits at scintigraphy are neither obligatory nor specific. Although the clinical significance of MB is still debated, MB has been associated with acute coronary syndrome, coronary vasospasm, and even sudden cardiac death. CONCLUSION: Although MB may lead to myocardial ischemia during stress, its clinical presentation and electrocardiographic findings are not specific.

Drug eluting balloon: a multipurpose tool for coronary revascularization with optimal long-term follow-up results.

AIMS: This study aimed to evaluate safety and efficacy of drug-coated balloon (DCB) at long-term follow-up; a large series of real-life patients underwent revascularization with DCB for a wide spectrum of clinical and angiographic situations. METHODS AND RESULTS: One hundred ten patients underwent percutaneous revascularization using paclitaxel eluting balloon (Sequent Please, Braun, Germany). End-points were major adverse cardiac events (MACE; all-cause death, myocardial infarction [MI], target vessel revascularisation [TVR], and vessel thrombosis). DCB were used for stable angina (58%), unstable angina/nonST elevation MI (31%) and ST elevation MI (11%). DCB were used for in-stent restenosis (61%), small vessel disease (25%), with bare metal stent (BMS) to avoid long dual antiplatelet therapy (10%) or for impossibility to place a stent (4%). Cumulative MACE at follow-up (median 23 months, IQR 13-32) was 12.7%, with 8.2% all-cause death (1 fatal MI), 4.5% TVR, 3.6% TLR, and no vessel thrombosis. Three of four TLRs occurred in patients who received DEB for DES restenosis. CONCLUSIONS: DCB are a very effective tool for a variety of clinical and angiographic situations. DCB use seems to be affected by a low rate of complications and adequate results at long-term follow-up.

Multimodality Imaging Approach for Planning and Guiding Direct Transcatheter Tricuspid Valve Annuloplasty.

Interest in transcatheter treatment of tricuspid regurgitation (TR) has grown significantly in recent years due to increasing evidence correlating TR severity with mortality and to limited availability of surgical options often considered high-risk in these patients. Although edge-to-edge repair is currently the main transcatheter therapeutic strategy, tricuspid valve direct annuloplasty can also be performed safely and effectively to reduce TR and improve heart failure symptoms and quality of life. In the annuloplasty procedure, an adjustable band is implanted around the tricuspid annulus to reduce valvular size and improve TR. Patient selection and careful preoperative imaging, including transthoracic echocardiography, transesophageal echocardiography, and computed tomography, are critical for procedural success and proper device implantation. Compared to edge-to-edge repair, perioperative imaging with transesophageal echocardiography and fluoroscopy is particularly challenging. Alignment and insertion of the anchors are demanding but essential to achieve good results and avoid damaging the surrounding structures. The presence of shadowing artifacts due to cardiac devices makes the acquisition of good-quality images even more challenging. In this review, we discuss the current role of multimodality imaging in planning direct transcatheter tricuspid valve annuloplasty and describe all procedural steps focusing on echocardiographic monitoring.

Optical Coherence Tomography in Myocardial Infarction Management: Enhancing Precision in Percutaneous Coronary Intervention.

In acute myocardial infarction (AMI), the urgency of coronary revascularization through percutaneous coronary intervention (PCI) is paramount, offering notable advantages over pharmacologic treatment. However, the persistent risk of adverse events, including recurrent AMI and heart failure post-revascularization, underscores the necessity for enhanced strategies in managing coronary artery disease. Traditional angiography, while widely employed, presents significant limitations by providing only two-dimensional representations of complex three-dimensional vascular structures, hampering the accurate assessment of plaque characteristics and stenosis severity. Intravascular imaging, specifically optical coherence tomography (OCT), significantly addresses these limitations with superior spatial resolution compared to intravascular ultrasound (IVUS). Within the context of AMI, OCT serves dual purposes: as a diagnostic tool to accurately identify culprit lesions in ambiguous cases and as a guide for optimizing PCI procedures. Its capacity to differentiate between various mechanisms of acute coronary syndrome, such as plaque rupture and spontaneous coronary dissection, enhances its diagnostic potential. Furthermore, OCT facilitates precise lesion preparation, optimal stent sizing, and confirms stent deployment efficacy. Recent meta-analyses indicate that OCT-guided PCI markedly improves safety and efficacy in revascularization, subsequently decreasing the risks of mortality and complications. This review emphasizes the critical role of OCT in refining patient-specific therapeutic approaches, aligning with the principles of precision medicine to enhance clinical outcomes for individuals experiencing AMI.

Prevalence of thyroid dysfunction and effect of contrast medium on thyroid metabolism in cardiac patients undergoing coronary angiography.

BACKGROUND: Iodinated contrast media (CM) may influence thyroid function. Precautions are generally taken in patients with hyperthyroidism, even if subclinical, whereas the risks in patients with hypothyroidism or low triiodothyronine (T3) syndrome are not considered as appreciable. PURPOSE: To assess the presence and type of thyroid dysfunction in patients admitted for coronary angiography (CA), to assess the concentration of free-iodide in five non-ionic CM, and to evaluate changes in thyroid function after CA in patients with low T3 syndrome. MATERIAL AND METHODS: We measured free T3, free thyroxine (T4), and thyroid-stimulating hormone (TSH) in 1752 consecutive patients prior to CA and free-iodide in five non-ionic CM. Urinary free-iodide before and 24 h after CA, and thyroid hormone profile 48 h after CA were also made in 17 patients with low T3 syndrome. Patients were followed up for an average duration of 63.5 months. RESULTS: The patients were divided into four groups: euthyroidism (60%), low T3 syndrome (28%), hypothyroidism (10%), and hyperthyroidism (2%). The free-iodide resulted far below the recommended limit of 50 µg/mL in all tested CM. In low T3 syndrome, 24-h free-iodide increased after CA from 99.9 ± 63 ug to 12276 ± 9285 ug (P < 0.0001). A reduction in TSH (4.97 ± 1.1 vs. 4.17 ± 1.1 mUI/mL, P < 0.01) and free T3 (1.44 ± 0.2 vs. 1.25 ± 0.3 pg/mL, P < 0.01), with an increase in free T4 (11.3 ± 2.9 vs. 12.5 ± 3.4 pg/dL, P < 0.001), was found. Patients with functional thyroid disease in the follow-up had a significant lower rate survival compared to euthyroid patients (90.7 vs. 82.2%, P < 0.00001). CONCLUSION: Thyroid dysfunction is frequent in patients who perform a CA, and low T3 syndrome is the predominant feature. The administration of contrast medium may further compromise the thyroid function.

The Role of Multimodality Imaging Approach in Acute Aortic Syndromes: Diagnosis, Complications, and Clinical Management.

Acute aortic syndromes are life-threatening conditions with high morbidity and mortality. The principal pathological feature is acute wall damage with possible evolution towards aortic rupture. Accurate and timely diagnosis is mandatory to avoid catastrophic consequences. Indeed, misdiagnosis with other conditions mimicking acute aortic syndromes is associated with premature death. In this view, cardiovascular imaging is necessary for the correct diagnosis and management. Echocardiography, computed tomography, magnetic resonance imaging, and aortography allow for diagnosis, guarantee immediate treatment, and detect associated complications. Multimodality imaging is essential in the diagnostic work-up to confirm or rule out acute aortic syndromes. The aim of this review is to highlight the contemporary evidence on the role of single cardiovascular imaging techniques and multimodality imaging in the diagnosis and management of acute aortic syndromes.

T(-786)→C polymorphism of the endothelial nitric oxide synthase gene is associated with insulin resistance in patients with ischemic or non ischemic cardiomyopathy.

BACKGROUND: Insulin resistance (IR) and endothelial dysfunction are frequently associated in cardiac disease. The T(-786)→C variant in the promoter region of the endothelial nitric oxide synthase (eNOS) gene has been associated with IR in both non-diabetic and diabetic subjects. Aim of the study was to assess the reciprocal relationships between T(-786)→C eNOS polymorphism and IR in ischemic and non-ischemic cardiomyopathy. METHOD: A group of 132 patients (108 males, median age 65 years) with global left ventricular (LV) dysfunction secondary to ischemic or non-ischemic heart disease was enrolled. Genotyping of T(-786)→C eNOS gene promoter, fasting glucose, insulin, and insulin resistance (defined as HOMA-IR index > 2.5) were determined in all patients. RESULTS: Genotyping analysis yielded 37 patients homozygous for the T allele (TT), 70 heterozygotes (TC) and 25 homozygous for C (CC). Patients with CC genotype had significantly higher systemic arterial pressure, blood glucose, plasma insulin and HOMA index levels than TT. At multivariate logistic analysis, the history of hypertension and the genotype were the only predictors of IR. In particular, CC genotype increased the risk of IR (CI% 1.4-15.0, p < 0.01) 4.5-fold. The only parameter independently associated with the extent of LV dysfunction and the presence of heart failure (HF) was the HOMA index (2.4 CI% 1.1-5.6, p < 0.04). CONCLUSIONS: T(-786)→C eNOS polymorphism was the major independent determinant of IR in a population of patients with ischemic and non-ischemic cardiomyopathy. The results suggest that a condition of primitive eNOS lower expression can predispose to an impairment of glucose homeostasis, which in turn is able to affect the severity of heart disease.

Myocardial perfusion scintigraphy for risk stratification of patients with coronary artery disease: the AMICO registry.

AIMS: We assessed the prognostic value of myocardial perfusion scintigraphy (MPS) with cadmium-zinc-telluride in addition to clinical and coronary anatomy analysis. METHODS AND RESULTS: We prospectively enrolled 1464 patients (26% females, 69.5 ± 10.4 years) referred for stress-rest MPS. All the patients underwent invasive coronary angiography (1171, 80%) or coronary computed tomography angiography (293, 20%). We defined a composite endpoint of cardiovascular death and non-fatal MI. After an 8-year follow-up, summed stress score (SSS) had the highest accuracy in predicting primary endpoint with a ROC-derived cut-off of SSS >8 (>10% myocardium). SSS >8 portended the lowest survival probability at Kaplan-Meier analysis (P < 0.0001 for the composite endpoint and individual components). The Cox-regression analysis indicated SSS as an independent predictor of the composite endpoint, along with fasting blood glucose and total cholesterol and contrary to coronary anatomy parameters. Patients with SSS >8 treated with optimal medical therapy (OMT) had the largest area of necrosis, the lower ischaemic burden, the most compromised LV systo-diastolic function and the highest LV mass, but received a less aggressive treatment in comparison to early revascularized patients. Survival analysis revealed patients with SSS ≤8 had the greater freedom from events, irrespective of the treatment strategy, while the group with SSS >8 and OMT had the worst outcome, followed by patients with SSS >8 and early revascularization (log-rank test: all P < 0.0001). CONCLUSION: MPS-SSS constitutes a strong independent predictor of future adverse events after adjustment for multiple clinical parameters and coronary angiography. In particular, MPS could help risk stratification of patients who did not undergo early revascularization.

Echocardiographic Biventricular Coupling Index to Predict Precapillary Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a frequent and detrimental condition. Right heart catheterization (RHC) is the gold standard to identify PH subtype (precapillary from postcapillary PH) and is key for treatment allocation. In this study, the novel echocardiographic biventricular coupling index (BCI), based on the ratio between right ventricular stroke work index and left ventricular E/E' ratio, was tested for the discrimination of PH subtype using RHC as the comparator. METHODS: BCI was derived in 334 consecutive patients who underwent transthoracic echocardiography and RHC for all indications. BCI was then tested in a validation cohort of 1,349 patients. RESULTS: The accuracy of BCI to identify precapillary PH was high in the derivation cohort (area under the curve, 0.82; 95% CI, 0.78-0.88; P < .001; optimal cut point, 1.9). BCI identified patients with precapillary PH with high accuracy also in the validation cohort (area under the curve, 0.87 [95% CI, 0.85-0.89; P < .001]; subgroup with PH: area under the curve, 0.91 [95% CI, 0.89-0.93; P < .001]; cut point, 1.9; sensitivity, 82%; specificity, 89%; positive predictive value, 77%; negative predictive value, 92%). BCI outperformed both the D'Alto score (Z = 3.56; difference between areas = 0.05; 95% CI, 0.02-0.07; P < .001) and the echocardiographic pulmonary-to-left atrial ratio index (Z = 2.88; difference between areas = 0.02; 95% CI, 0.01-0.04; P = .004). CONCLUSIONS: BCI is a novel, noninvasive index based on routinely available echocardiographic parameters that identifies with high accuracy patients with precapillary PH. BCI may be of value in the screening workup of patients with PH.

Central apnoeas and ticagrelor-related dyspnoea in patients with acute coronary syndrome.

AIMS: Dyspnoea often occurs in patients with acute coronary syndrome (ACS) treated with ticagrelor compared with other anti-platelet agents and is a cause of drug discontinuation. We aimed to explore the contribution of central apnoeas (CA) and chemoreflex sensitization to ticagrelor-related dyspnoea in patients with ACS. METHODS AND RESULTS: Sixty consecutive patients with ACS, preserved left ventricular ejection fraction, and no history of obstructive sleep apnoea, treated either with ticagrelor 90 mg b.i.d. (n = 30) or prasugrel 10 mg o.d. (n = 30) were consecutively enrolled. One week after ACS, all patients underwent two-dimensional Doppler echocardiography, pulmonary static/dynamic testing, carbon monoxide diffusion capacity assessment, 24-h cardiorespiratory monitoring for hypopnoea-apnoea detection, and evaluation of the chemosensitivity to hypercapnia by rebreathing technique. No differences were found in baseline demographic and clinical characteristics, echocardiographic, and pulmonary data between the two groups. Patients on ticagrelor, when compared with those on prasugrel, reported more frequently dyspnoea (43.3% vs. 6.7%, P = 0.001; severe dyspnoea 23.3% vs. 0%, P = 0.005), and showed higher apnoea-hypopnoea index (AHI) and central apnoea index (CAI) during the day, the night and the entire 24-h period (all P < 0.001). Similarly, they showed a higher chemosensitivity to hypercapnia (P = 0.001). Among patients treated with ticagrelor, those referring dyspnoea had the highest AHI, CAI, and chemosensitivity to hypercapnia (all P < 0.05). CONCLUSION: Central apnoeas are a likely mechanism of dyspnoea and should be screened for in patients treated with ticagrelor. A drug-related sensitization of the chemoreflex may be the cause of ventilatory instability and breathlessness in this setting.

Amyloid Deposits and Fibrosis on Left Ventricular Endomyocardial Biopsy Correlate With Extracellular Volume in Cardiac Amyloidosis.

Background The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. Methods and Results We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68-81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%-30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%-23%; range, 5%-60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. Conclusions Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone.

A novel echocardiographic method for estimation of pulmonary artery wedge pressure and pulmonary vascular resistance.

AIMS: This study aimed to evaluate a novel echocardiographic algorithm for quantitative estimation of pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR) in patients with heart failure and pulmonary hypertension (PH) scheduled to right heart catheterization (RHC). METHODS AND RESULTS: In this monocentric study, 795 consecutive patients (427 men; age 68.4 ± 12.1 years) undergoing echocardiography and RHC were evaluated. Multiple regression analysis was performed to identify echocardiographic predictors of PAWP and PVR measured by RHC in the derivation group (the first 200 patients). The diagnostic accuracy of the model was then tested in the validation group (the remaining 595 patients). PH was confirmed by RHC in 507 (63.8%) patients, with 192 (24.2%) cases of precapillary PH, 248 (31.2%) of postcapillary PH, and 67 (8.4%) of combined PH. At regression analysis, tricuspid regurgitation maximal velocity, mitral E/e' ratio, left ventricular ejection fraction, right ventricular fractional area change, inferior vena cava diameter, and left atrial volume index were included in the model (R = 0.8, P < 0.001). The model showed a high diagnostic accuracy in estimating elevated PAWP (area under the receiver operating characteristic curve = 0.97, 92% sensitivity, and 93% specificity, P < 0.001) and PVR (area under the receiver operating characteristic curve = 0.96, 89% sensitivity, and 92% specificity, P < 0.001), outperforming 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations (P < 0.001) and Abbas' equation (P < 0.001). Bland-Altman analysis showed satisfactory limits of agreement between echocardiography and RHC for PAWP (bias 0.7, 95% confidence interval -7.3 to 8.7) and PVR (bias -0.1, 95% confidence interval -2.2 to 1.9 Wood units), without indeterminate cases. CONCLUSIONS: A novel quantitative echocardiographic approach for the estimation of PAWP and PVR has high diagnostic accuracy in patients with heart failure and PH.