Cardiopulmonary transit time: A novel PET imaging biomarker of in vivo physiology for risk stratification of heart transplant recipients.

BACKGROUND: Myocardial blood flow (MBF) can be quantified using dynamic PET studies. These studies also inherently contain tomographic images of early bolus displacement, which can provide cardiopulmonary transit times (CPTT) as measure of cardiopulmonary physiology. The aim of this study was to assess the incremental prognostic value of CPTT in heart transplant (OHT) recipients. METHODS: 94 patients (age 56 ± 16 years, 78% male) undergoing dynamic 13N-ammonia stress/rest studies were included, of which 68 underwent right-heart catherization. A recently validated cardiac allograft vasculopathy (CAV) score based on PET measures of regional perfusion, peak MBF and left-ventricular (LV) ejection fraction (LVEF) was used to identify patients with no, mild or moderate-severe CAV. Time-activity curves of the LV and right ventricular (RV) cavities were obtained and used to calculate the difference between the LV and RV bolus midpoint times, which represents the CPTT and is expressed in heartbeats. Patients were followed for a median of 2.5 years for the occurrence of major adverse cardiac events (MACE), including cardiovascular death, hospitalization for heart failure or acute coronary syndrome, or re-transplantation. RESULTS: CPTT was significantly correlated with cardiac filling pressures (r = .434, P = .0002 and r = .439, P = .0002 for right atrial and pulmonary wedge pressure), cardiac output (r = - .315, P = .01) and LVEF (r = - .513, P < .0001). CPTT was prolonged in patients with MACE (19.4 ± 6.0 vs 14.5 ± 3.0 heartbeats, P < .001, N = 15) with CPTT ≥ 17.75 beats showing optimal discriminatory value in ROC analysis. CPTT ≥ 17.75 heartbeats was associated with a 10.1-fold increased risk (P < .001) of MACE and a 7.3-fold increased risk (P < .001) after adjusting for PET-CAV, age, sex and time since transplant. CONCLUSION: Measurements of cardiopulmonary transit time provide incremental risk stratification in OHT recipients and enhance the value of multiparametric dynamic PET imaging, particularly in identifying high-risk patients.

Visceral adiposity and left ventricular remodeling: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Visceral fat (VF) is a source of pro-inflammatory adipokines implicated in cardiac remodeling. We sought to determine the impact of visceral fat and subcutaneous fat (SQ) depots on left ventricular (LV) structure, function, and geometry in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: We performed a post-hoc analysis on 1151 participants from MESA with cardiac magnetic resonance quantification of LV mass and LV mass-to-volume ratio (LVMV, an index of concentricity) and computed tomographic-derived SQ and VF area. Multivariable regression models to estimate association between height-indexed SQ and VF area (per cm(2)/m) with height-indexed LV mass (per height(2.7)) and LVMV were constructed, adjusted for clinical, biochemical, and demographic covariates. We found that both VF and SQ area were associated with height-indexed LV mass (ρ = 0.36 and 0.12, P < 0.0001, respectively), while only VF area was associated with LVMV (ρ = 0.28, P < 0.0001). Individuals with above-median VF had lower LV ejection fraction, greater indexed LV volumes and mass, and higher LVMV (all P < 0.001). In multivariable models adjusted for weight, VF (but not SQ) area was associated with LV concentricity and LV mass index, across both sexes. CONCLUSION: Visceral adiposity is independently associated with LV concentricity, a precursor to heart failure. Further study into the role of VF in LV remodeling as a potential therapeutic target is warranted.

Computed tomographic angiography measures of coronary plaque in clinical trials: opportunities and considerations to accelerate drug translation.

Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval. For many disease areas, nearly a half of drugs are approved by the U.S. Food & Drug Administration based on beneficial effects on surrogate endpoints. For cardiovascular disease, only low-density lipoprotein cholesterol and blood pressure are approved as surrogates for cardiovascular disease. Valid surrogates of CAD are urgently needed to facilitate robust evaluation of novel, beneficial treatments and inspire investment. Fortunately, advances in non-invasive imaging offer new opportunity for accelerating CAD drug development. Coronary computed tomography angiography (CCTA) is the most advanced candidate, with the ability to measure accurately and reproducibly characterize the underlying causal disease itself. Indeed, favourable changes in plaque burden have been shown to be associated with improved outcomes, and CCTA may have a unique role as an effective surrogate endpoint for therapies that are designed to improve CAD outcomes. CCTA also has the potential to de-risk clinical endpoint-based trials both financially and by enrichment of participants at higher likelihood of MACE. Furthermore, total non-calcified, and high-risk plaque volume, and their change over time, provide a causally linked measure of coronary artery disease which is inextricably linked to MACE, and represents a robust surrogate imaging biomarker with potential to be endorsed by regulatory authorities. Global consensus on specific imaging endpoints and protocols for optimal clinical trial design is essential as we work towards a rigorous, sustainable and staged pathway for new CAD therapies.

Lymphocytic myocarditis presenting as unexplained ventricular arrhythmias: diagnosis with endomyocardial biopsy and response to immunosuppression.

During a period of 18 months beginning in January 1982, a total of 65 patients were referred to the Miami Heart Institute for evaluation of either aborted out of hospital sudden death, ventricular tachycardia resistant to standard clinically directed antiarrhythmic medication programs or high grade ventricular arrhythmia (Lown class greater than or equal to IV B) with or without syncope. After complete evaluation including cardiac catheterization in all but 1 patient, 17 patients were identified in whom no obvious cardiac disease could be found. Twelve of the 17 underwent right ventricular endomyocardial biopsy. Six of the 12 biopsies demonstrated clinically unsuspected lymphocytic myocarditis (Group A). Findings in three of the remaining six biopsies were consistent with an early cardiomyopathy and in three were completely normal (Group B). Retrospective review of the clinical, laboratory, electrophysiologic, hemodynamic and angiographic data failed to identify a marker that reliably separated Group A from Group B patients. In addition to antiarrhythmic therapy guided by laboratory electrophysiologic study, all Group A patients were treated with prednisone and azathioprine. After 6 months of immunosuppression, all patients with myocarditis were reevaluated in the hospital without antiarrhythmic medication. Ventricular tachycardia/fibrillation could not be provoked in the laboratory during repeat electrophysiologic testing in five of the six patients. Repeat myocardial biopsy after all immunosuppressive therapy had been discontinued revealed absence of inflammation associated with varying degrees of residual interstitial fibrosis. There were no deaths. It was concluded that a patient with an otherwise clinically silent lymphocytic myocarditis can present with potentially life-threatening ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of cardiac CT and calcium scoring for detecting coronary plaque: implications on prognosis and patient management.

Clinicians often use risk factor-based calculators to estimate an individual's risk of developing cardiovascular disease. Non-invasive cardiovascular imaging, particularly coronary artery calcium (CAC) scoring and coronary CT angiography (CTA), allows for direct visualization of coronary atherosclerosis. Among patients without prior coronary artery disease, studies examining CAC and coronary CTA have consistently shown that the presence, extent and severity of coronary atherosclerosis provide additional prognostic information for patients beyond risk factor-based scores alone. This review will highlight the basics of CAC scoring and coronary CTA and discuss their role in impacting patient prognosis and management.

Endomyocardial fibrosis. Preoperative diagnosis and surgical therapy.

The case of a Nigerian student with biventricular endomyocardial fibrosis is presented. Diagnosis was suggested by cardiac catheterization and histologically confirmed by a percutaneous endomyocardial biopsy. Successful surgical repair including mitral valve replacement, tricuspid valve reconstruction, and left ventricular endomyocardial resection was performed through a biatrial approach. The pathologic and surgical considerations are reviewed. This is one of the few cases of endomyocardial fibrosis reported from the United States and the first in which a percutaneous endomyocardial biopsy was used to provide a definitive preoperative histologic diagnosis.

Macroreentry as a mechanism of atrial-induced ventricular ectopic beats: a laboratory curiosity?

During electrophysiologic study in a patient, programmed stimulation of the atrium induced fixed coupled ventricular premature beats on the basis of intraventricular macroreentry. This type of macroreentry, which was reproducible, appears to have been merely a "laboratory curiosity" and never played a clinical role in this patient with chronic recurrent ventricular tachycardia.

Thallium-201 myocardial scintigraphy in patients with triple-vessel disease and ischemic exercise stress tests.

Thirty patients with triple-vessel coronary artery disease proven by angiography, symptomatic angina and a positive ECG stress test were evaluated with thallium-201 (201TI) scintigraphy. Twenty patients also had aortocoronary saphenous vein bypass surgery; 15 of them had repeat noninvasive evaluation. Seventy percent of these patients showed ischemia by 201TI scintigraphy, of which one-half returned to normal after surgery. Postoperative reversion of the ECG stress test together with 201TI stress/reperfusion imaging correlated well with the completeness of surgical revascularization. We could not explain the prevalence (80%) of infarcts detected by 201TI in this group, of which 76% could be anatomically correlated to epicardial scars. The positivity of infarcts by 201TI exceeded that predicted by previous history of infarction, Q waves on resting ECG or ventriculographic akinesis. These observations suggest that 201TI scintigraphy is a useful noninvasive tool in the follow-up and understanding of patients with coronary heart disease. These conclusions also support the concept that 201TI stress imaging need not have the identical connotation as the ECG stress test.