Early detection of cancer therapy cardiotoxicity by radionuclide angiography: An update.

Cancer therapy-induced cardiotoxicity is an emerging clinical and healthcare issue. Myocardial dysfunction and heart failure are mostly responsible for increased cardiovascular mortality in cancer disease survivors. Several imaging surveillance techniques have been proposed for early diagnosis of cancer therapy-induced cardiac dysfunction. Our aim was to provide an update of radionuclide angiography applications in this field. Radionuclide angiography is widely used to assess left ventricular ejection fraction (LVEF) throughout cancer treatment, especially in patients with limited acoustic window. Additional prognostic data may be provided by phase analysis and diastolic function evaluation. Low LVEF and high approximate entropy at baseline seem to be predictors for cancer therapy-induced cardiac dysfunction. A decrease in peak filling rate and/or an increase in time to peak filling rate may be observed in patients undergoing anthracycline and/or trastuzumab administration. Diastolic function impairment may precede or not LVEF decrease. In conclusion, recent studies have provided novel insights into the possible role of radionuclide angiography in the early detection of cancer therapy cardiotoxicity. While interpreting the results of a radionuclide angiography examination, an integrated approach combining the evaluation of LVEF, LV diastolic function, and phase analysis may be useful to improve risk stratification of cancer patients treated with cardiotoxic agents.

Single-photon cardiac imaging in patients with cardiac implantable electrical devices.

Nuclear imaging techniques like single-photon emission computed tomography (SPECT) and radionuclide angiography have wide applications in patients receiving a cardiac implantable electrical device (CIED), who cannot usually undergo cardiac magnetic resonance. Our aim was to provide an update of single-photon imaging clinical applications, with a specific focus on CIED recipients. SPECT imaging is commonly used in CIED patients to assess myocardial perfusion, but it can also be used to evaluate myocardial viability, which is an important predictor of LV function improvement by cardiac resynchronization therapy (CRT). Radionuclide angiography has shown higher temporal resolution and reproducibility than SPECT in the evaluation of cardiac function and dyssynchrony. Left ventricular dyssynchrony as assessed by radionuclide angiography with phase analysis may be reliably used for CRT patient selection and evaluation of CRT response. SPECT imaging with meta-iodo-benzyl-guanidine allows for cardiac sympathetic innervation examination, which may be used for prognostic stratification of heart failure patients and prediction of ventricular tachyarrhythmias. Finally, promising results in CIED infection diagnosis have been shown by SPECT with radiolabeled autologous white blood cells.

Effects of cardiac resynchronization therapy on right ventricular function during rest and exercise, as assessed by radionuclide angiography, and on NT-proBNP levels.

AIM: We carried out this study to investigate mid-term effects of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and neurohormonal response, expressed by N-terminal pro-brain natriuretic peptide (NT-proBNP), in heart failure patients stratified by baseline RV ejection fraction (RVEF). METHODS AND RESULTS: Thirty-six patients with nonischemic dilated cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. Plasma NT proBNP was assessed before implantation and after 3 months. At baseline, RVEF was impaired (≤35%) in 14 patients, preserved (>35%) in 22. At 3 months, RVEF improved during rest and exercise (P = .02) in patients with impaired RV function, while remaining unchanged in patients with preserved RV function. Rest and exercise RV dyssynchrony decreased in both groups at follow-up (P < .05). A similar mid-term improvement in left ventricular (LV) function and NT-proBNP was observed in patients with impaired and preserved RVEF. In the former, the decrease in NT-proBNP correlated with the improvements both in LV and RV dyssynchrony and functions. CONCLUSION: CRT may improve RV performance, during rest and exercise, and neurohormonal response in heart failure patients with nonischemic dilated cardiomyopathy and baseline RV dysfunction. RV dysfunction should not be considered per se a primary criterion for excluding candidacy to CRT.

Interplay of coronary angiography and intravascular ultrasound in predicting long-term outcomes after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the major cause of late graft-related death after heart transplantation (HT). Identification of patients at risk of cardiovascular events has relevant implications in appropriately guiding resources and intensity of follow-up. In this context, the prognostic relevance of serial coronary imaging long-term after HT is unexplored. METHODS: Recipients with intravascular ultrasound (IVUS) and coronary angiography performed 1 and 5 years after HT were monitored for subsequent 1 to 10 years to analyze the association of serial coronary imaging with cardiovascular death and major cardiovascular events (MACEs). RESULTS: Included were 131 patients. The MACE incidence was 31.8 per 1,000 patient-years, and cardiovascular mortality was 17.4 per 1,000 patient-years. Progression of coronary lesions detected by angiography and changes in IVUS-defined parameters, including an increase in maximal intimal thickness (MIT) ≥0.35 mm and vascular remodeling, predicted MACE occurrence. However, only MIT change ≥0.35 mm also predicted cardiovascular mortality. Among patients with normal or stable angiography, an MIT change ≥0.35 mm identified those with a significantly higher MACE rate (80 vs 13 events/1,000 patient-years). Worsening metabolic parameters appeared associated with the increasing severity of CAV development. CONCLUSIONS: Combined imaging analysis of progression of angiographic lesions and IVUS-detected MIT between 1 and 5 years post-HT allows discriminating patients at high, intermediate, and low risk for adverse long-term cardiovascular outcomes. The metabolic syndrome milieu is confirmed as a key risk factor for long-term CAV progression and adverse prognosis.

Occurrence of Fatal and Nonfatal Adverse Outcomes after Heart Transplantation in Patients with Pretransplant Noncytotoxic HLA Antibodies.

HLA antibodies (HLA ab) in transplant candidates have been associated with poor outcome. However, clinical relevance of noncytotoxic antibodies after heart transplant (HT) is controversial. By using a Luminex-based HLA screening, we retested pretransplant sera from HT recipients testing negative for cytotoxic HLA ab and for prospective crossmatch. Out of the 173 consecutive patients assayed (52 ± 13y; 16% females; 47% ischemic etiology), 32 (18%) showed pretransplant HLA ab, and 12 (7%) tested positive against both class I and class II HLA. Recipients with any HLA ab had poorer survival than those without (65 ± 9 versus 82 ± 3%; P = 0.02), accounting for a doubled independent mortality risk (P = 0.04). In addition, HLA-ab detection was associated with increased prevalence of early graft failure (35 versus 15%; P = 0.05) and late cellular rejection (29 versus 11%; P = 0.03). Of the subgroup of 37 patients suspected for antibody mediated rejection (AMR), the 9 with pretransplant HLA ab were more likely to display pathological AMR grade 2 (P = 0.04). By an inexpensive, luminex-based, HLA-screening assay, we were able to detect non-cytotoxic HLA ab predicting fatal and nonfatal adverse outcomes after heart transplant. Allocation strategies and desensitization protocols need to be developed and prospectively tested in these patients.

QRS pattern and improvement in right and left ventricular function after cardiac resynchronization therapy: a radionuclide study.

BACKGROUND: Predicting response to cardiac resynchronization therapy (CRT) remains a challenge. We evaluated the role of baseline QRS pattern to predict response in terms of improvement in biventricular ejection fraction (EF). METHODS: Consecutive patients (pts) undergoing CRT implantation underwent radionuclide angiography at baseline and at mid-term follow-up. The relationship between baseline QRS pattern and mechanical dyssynchrony using phase analysis was evaluated. Changes in left and right ventricular EF (LVEF and RVEF) were analyzed with regard to baseline QRS pattern. RESULTS: We enrolled 56 pts, 32 with left bundle branch block (LBBB), 4 with right bundle branch block (RBBB) and 20 with non-specific intraventricular conduction disturbance (IVCD). A total of 48 pts completed follow-up. LBBB pts had significantly greater improvement in LVEF compared to RBBB or non-specific IVCD pts (+9.6 ± 10.9% vs. +2.6 ± 7.6%, p = 0.003). Response (defined as ≥ 5% increase in LVEF) was observed in 68% of LBBB vs. 24% of non-specific IVCD pts (p = 0.006). None of the RBBB pts were responders. RVEF was significantly improved in LBBB (+5.0 ± 9.0%, p = 0.007), but not in non-specific IVCD and RBBB pts (+0.4 ± 5.8%, p = 0.76). At multivariate analysis, LBBB was the only predictor of LVEF response (OR, 7.45; 95% CI 1.80-30.94; p = 0.006), but not QRS duration or extent of mechanical dyssynchrony. CONCLUSIONS: Presence of a LBBB is a marker of a positive response to CRT in terms of biventricular improvement. Pts with non-LBBB pattern show significantly less benefit from CRT than those with LBBB.

Cyclosporine lowering with everolimus versus mycophenolate mofetil in heart transplant recipients: long-term follow-up of the SHIRAKISS randomized, prospective study.

BACKGROUND: Cyclosporine nephrotoxicity negatively impacts long-term outcome after heart transplantation (HT). We previously reported 1-year results from a randomized study showing that cyclosporine-lowering strategies based on everolimus or mycophenolate mofetil (MMF) are equally effective for reducing progression of renal dysfunction. It is unknown whether this efficacy could be maintained over the long term. METHODS: Thirty-four recipients 1 to 4 years after HT and with 25 to 60 ml/min of creatinine clearance (CrCl) were randomized to everolimus with a very low dose (C(0): 50 to 90 ng/ml, n = 17) or MMF with low dose of cyclosporine (C(0): 100 to 150 ng/ml, n = 17). Follow-up was prolonged up to 3 years, and calculated CrCl was the main efficacy measure. RESULTS: Cyclosporine was maintained at 70% and 30% lower than baseline in the everolimus and MMF arms, respectively, throughout the 3-year study period. CrCl remained stable in the everolimus patients (+7% from baseline; p = 0.7), but improved in the MMF patients (+20% from baseline; p < 0.01), with a trend toward improved values compared with everolimus patients (46 ± 12 vs 56 ± 15 ml/min; p = 0.06). Subgroup analysis revealed that baseline proteinuria markedly influenced the renal function response to everolimus: whereas in patients with baseline proteinuria CrCl significantly worsened (-20%; p = 0.04), it improved in those without (+15%; p = 0.03). Safety was comparable between the two study arms. CONCLUSIONS: Cyclosporine nephrotoxicity improved after a prolonged dose reduction in patients receiving MMF. The everolimus-based strategy provided a similar benefit only to patients without baseline proteinuria. While raising caution against the universal use of everolimus for kidney protection, our long-term results support the need for customized approaches in the management of drug toxicities in maintenance HT recipients.

Safety and efficacy of early aggressive versus cholesterol-driven lipid-lowering strategies in heart transplantation: a pilot, randomized, intravascular ultrasound study.

BACKGROUND: Statins are recommended in heart transplantation regardless of lipid levels. However, it remains unknown whether dosing should be maximized or adjusted toward a pre-defined cholesterol threshold. METHODS: This pilot, randomized, open-label study compares an early maximal dose of fluvastatin (80 mg/day) with a strategy based on 20 mg/day subsequently titrated to target low-density lipoproteins (LDL) <100 mg/dl. Efficacy outcomes consisted of achieving an LDL level of <100 mg/dl at 12 months after transplant, and change in intracoronary ultrasound parameters. RESULTS: Fifty-two patients were randomized. Overall safety, and efficacy in achieving LDL targets (13 [50%] vs 14 [54%]; p = 0.8) were comparable between study arms, but 17 (65%) patients needed a dose increase in the titrated-dosing arm. Early LDL levels and average LDL burden were lower in the maximal-dosing arm (p < 0.05). Few patients developed an increase in maximal intimal thickness of >0.5 mm, with numerical prevalence in the titrated-dosing arm (3 [12.5%] vs 1 [5%]; p = 0.3). Intimal volume increased in the titrated-dosing (p < 0.01) but not in the maximal-dosing arm (p = 0.1), which accordingly showed a higher prevalence of negative remodeling (p = 0.02). CONCLUSIONS: Despite being as effective as the titrated-dosing approach in achieving LDL <100 mg/dl at 12 months after transplant, the maximal-dose approach was associated with a more rapid effect and with potential advantages in preventing pathologic changes in graft coronary arteries.

Radionuclide angiographic determination of regional left ventricular systolic function during rest and exercise in patients with nonischemic cardiomyopathy treated with cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) can improve global left ventricular (LV) function. However, limited data are available on regional LV contractility at rest and during exercise. The aim of the present study was to prospectively investigate the effects of CRT on regional LV ejection fraction (EF), global LVEF, and dyssynchrony, during rest and exercise, using radionuclide angiography. A total of 32 consecutive patients with heart failure and nonischemic cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. The regional EF was assessed in the interventricular septum and the lateral wall (LW). Intraventricular dyssynchrony was evaluated using Fourier phase analysis. During spontaneous rhythm, the EF was severely depressed in the septum compared to in the LW. CRT improved septal EF at rest and during exercise both at baseline (p <0.001) and after 3 months (p <0.05). The basal LW EF decreased during CRT (p <0.05, both at rest and during exercise). LV dyssynchrony decreased both at baseline and during follow-up, and the global LVEF showed improvement only at 3 months (p <0.001). In conclusion, in patients with nonischemic cardiomyopathy, CRT affects regional LV function by increasing the septal EF and reducing LW contractility, both at rest and during exercise. This was associated with an improvement in global LVEF and dyssynchrony.

Prophylaxis versus preemptive anti-cytomegalovirus approach for prevention of allograft vasculopathy in heart transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection may influence the development of cardiac allograft vasculopathy (CAV). Prophylactic or preemptive administration of anti-CMV agents effectively prevents acute CMV manifestations. However, studies comparing allograft-related outcomes between these anti-CMV approaches are lacking. Herein we report a longitudinal observational study comparing CAV development between prophylactic and preemptive approaches. METHODS: The 1-year change in maximal intimal thickening (MIT) assessed by intravascular ultrasound at 1 and 12 months after heart transplantation (the major surrogate for late survival) was compared in groups of patients routinely assigned to a preemptive strategy (from November 2004 to October 2005; n = 21) or receiving valganciclovir prophylaxis (from November 2005 to October 2006; n = 19). CMV infection was monitored with pp65 antigenemia. RESULTS: The 1-year increase in MIT was significantly lower in patients receiving prophylaxis compared with those managed preemptively (0.15 +/- 0.17 vs 0.31 +/- 0.20 mm; p = 0.01). Prophylaxed recipients presented less frequently with MIT change > or =0.3 mm (p = 0.03) and > or =0.5 mm (p = 0.10) than those managed preemptively. Prophylaxis was also associated with later onset of CMV infection (p = 0.01), lower peak CMV detection (p < 0.01) and reduced incidence of CMV disease/syndrome (p = 0.04). After adjusting for metabolic risk factors and other possible confounders, prophylaxis remained independently associated with lower risk for MIT change > or =0.3 mm (odds ratio = 0.09, 95% confidence interval 0.01 to 0.93; p = 0.04). CONCLUSIONS: Universal prophylaxis was associated with delayed onset of CMV infection, lower viral burden, reduced CMV disease/syndrome and less intimal thickening, as compared with a preemptive anti-CMV approach. Randomized studies are required to confirm the potential benefits of prophylaxis vs a preemptive approach in heart transplant recipients.

Safety and efficacy of ezetimibe with low doses of simvastatin in heart transplant recipients.

Although statins have proven efficacy in lowering lipids and improving survival in heart transplantation (HT) recipients, potential drug interactions may limit efficacy and reduce tolerability. This observational study explored the efficacy and tolerability of ezetimibe (10 mg/day) combined with simvastatin (10 or 20 mg/day) prescribed to HT recipients with intolerance to statins (n = 11) or inadequate lipid control despite high-dose statins (n = 14). Substantial reductions in lipid levels were apparent after 2 months (total cholesterol, -22%; low-density lipoproteins, -28%; triglycerides, -31%) and were maintained at 6 months. Reductions were significant in both subgroups of recipients; the vast majority (12 of 14, 85%) of recipients with a history of statins intolerance were able to tolerate ezetimibe plus low-dose simvastatin. This study provides suggestive evidence that treatment with ezetimibe plus low-dose simvastatin is well tolerated by HT recipients and may be effective for treatment of dyslipidemia in HT recipients with statins intolerance or resistance.

Long-term effect of folic acid therapy in heart transplant recipients: follow-up analysis of a randomized study.

BACKGROUND: Folic acid therapy reduces homocysteine plasma levels, which seem to influence occurrence of cardiac allograft vasculopathy, but its effect on medium- or long-term prognosis after heart transplantation is unknown. METHODS: We analyzed 7-year outcome of 51 recipients randomized to receive 15 mg/day of methyltertrahydrofolate for 1 year after heart transplantation or standard therapy alone (originally, for intravascular ultrasound study of short-term cardiac allograft vasculopathy progression); recipients were observed for a further 5 to 6 years. RESULTS: Overall, 13 deaths occurred (six oncologic, five cardiovascular, two infective). Estimated 7-year survival was better in recipients randomized to folate (88%+/-6% vs. 61%+/-9%, P=0.04). After adjusting for age, pretransplant coronary artery disease, and hyperhomocysteinemia, posttransplant folic acid therapy was associated with lower mortality (relative risk [RR] 0.53, 95% confidence interval [CI] 0.25-0.97; P=0.036), apparently driven by reductions in both cancer-related and cardiovascular causes. Reduced mortality was marked in a high-risk subgroup comprising older recipients and patients transplanted because of coronary artery disease (RR 0.43, 95% CI 0.17-0.85) but not in the lower-risk subgroup (RR 1.11, 95% CI 0.22-5.61). CONCLUSIONS: Although further studies are needed, it seems reasonable to suggest folate therapy to heart transplant recipients. It is possible that properties other than homocysteine reduction may provide antitumoral benefits.

Age and heart transplantation: results from a heart failure management unit.

BACKGROUND: More evidence is needed to assess the pros and cons of maintaining age-limit policies in heart transplantation (HT). METHODS: We analyzed clinical data from a heart failure management unit to investigate the impact of age on prognosis of two distinct cohorts: (i) 309 patients (median age, 57 yr; 62% male) with severe chronic heart failure (CHF) consecutively screened for HT; (ii) 336 HT recipients (median age 56 yr, 82% male). RESULTS: In CHF patients (screened for HT), prognosis was conditioned by the underlying severity of cardiac disease (i.e., New York Heart Association class III-IV, decreasing blood pressure, presence of atrial fibrillation and severe mitral regurgitation), whereas increasing age showed no sign of predicting all-cause or cardiovascular mortality (both p > or = 0.4). In HT recipients, age did not retain significance at multivariate analysis as an independent predictor (p > or = 0.14 for both all-cause and cardiovascular death), whereas ischemic etiology of pre-existing CHF did (p < or = 0.02). CONCLUSIONS: Age did not appear to be a primary determinant of all-cause or cardiovascular mortality among potential HT candidates or eventual recipients (ischemic etiology of CHF turned out to be the major determinant of post-transplant outcome). These results support the concept that HT may be considered a treatment option in patients with more advanced age strata, particularly when affected by non-ischemic cardiomyopathy.

[Coronary allograft vasculopathy: pathophysiological interaction between the immune system, infections and metabolic syndrome]. / La malattia coronarica del cuore trapiantato: interazione fisiopatologica tra sistema immunitario, infezioni e sindrome metabolica.

Cardiac allograft vasculopathy is still the main cause of long-term graft loss after heart transplantation. Indeed, recent advances in immunosuppression management led to a significant improvement in short-term survival, while long-term death rate did not change significantly in the last 20 years. In this paper, we will review the latest advances in the understanding of this peculiar form of atherosclerosis, focusing on the mechanisms that can be potentially targeted by specific therapeutic interventions.

Effects of cardiac resynchronization therapy on diastolic function: evaluation by radionuclide angiography.

While the beneficial effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) systolic function have been demonstrated, no information is available regarding its effects on LV diastolic function during exercise. Using radionuclide angiography, we prospectively evaluated the effects of CRT on diastolic function at rest and during exercise in 15 patients consecutively referred for CRT. All patients underwent equilibrium Tc(99) radionuclide angiography with bicycle exercise performed (1) at baseline; (2) immediately after CRT implantation, in spontaneous rhythm and during CRT; and (3) after 3 months of biventricular stimulation. Diastolic function was assessed by measurements of peak filling rate (PFR). At baseline, activation of biventricular stimulation influenced PFR neither at rest (1.06 +/- 0.34 vs 1.07 +/- 0.50 mL/s during spontaneous rhythm, P = 0.9) nor during exercise (1.45 +/- 0.62 vs 1.33 +/- 0.48 mL/s, P = 0.3). At 3 months, improvements were observed in New York Heart Association functional class and systolic function. By contrast, no improvement in diastolic function was observed either at rest (PFR = 1.11 +/- 0.45 vs 1.07 +/- 0.50 mL/s in spontaneous rhythm at baseline, P = 0.6) or during exercise (1.23 +/- 0.50 vs 1.33 +/- 0.48 mL/s, P = 0.2). These observations indicate that the intermediate benefits conferred by CRT on LV systolic function at rest and during exercise were not accompanied by similar improvements in diastolic function.

Relevance of cardioverter defibrillators for the prevention of sudden cardiac death on the timing of heart transplantation.

UNLABELLED: Information on the incidence of decompensation of chronic heart failure (CHF) in heart transplantation (HT) candidates eligible for prophylactic implantable cardioverter defibrillators (ICD) could provide insights into the influence of ICD on the timing for HT. METHODS: We investigated the prevalence of candidates satisfying SCD-HeFT and MADIT-II criteria for prophylactic ICD among patients (n = 317) with CHF referred to our tertiary center for HT. In addition to standard clinical and laboratory assessments, baseline evaluation included two-dimensional standard transthoracic echocardiogram and 12-lead electrocardiogram. RESULTS: At baseline, 19% of patients (n = 60) satisfied MADIT II criteria, and 58% (n = 185) fulfilled SCD-HeFT criteria. A total of 60% patients (n = 190) were eligible for prophylactic ICD implantation according to at least one set of criteria. Five-yr CHF decompensation-free survival was 68 +/- 4% in patients eligible for prophylactic ICD (p = 0.003), (RR 2.5, 95% CI 1.35-4.63). CONCLUSIONS: SCD-HeFT could imply a threefold rise in ICD eligibility in tertiary settings. As ICD-eligible patients would likely remain at high risk of progressive ventricular dysfunction, strict follow-up should be considered extremely important to allow a timely referral for HT.

Prognostic implications of serial assessments of pulmonary hypertension in severe chronic heart failure.

BACKGROUND: It is unknown whether time-related changes of pulmonary hypertension (PH) have prognostic relevance in severe chronic heart failure (CHF). METHODS: All CHF patients referred for follow-up from 1996 through 2003 were screened for this study. Eligibility depended on availability of a concomitant clinical, laboratory, electrocardiographic (ECG), echocardiographic and right-heart catheterization (RHC) assessment at index evaluation, as well as absence of pre-capillary PH. RESULTS: One hundred ninety-six patients (age 54 +/- 9 years; 27% women, 73% men; 50% in New York Heart Association [NYHA] Class III or IV) were included. PH at index evaluation was an independent predictor of acute heart failure or cardiovascular death (AHF/CD), with adjusted risk ratio (RR) = 2.30, 95% confidence interval (CI) 1.42 to 3.73 and p < 0.001. A pre-study (> or =6 months) RHC was available for 174 of the 196 patients. Worsening of mean pulmonary artery pressure (mPAP) of > or =30% (a pre-specified cut-off corresponding to the 75th percentile of DeltamPAP%) provided prognostic information independent of all index-evaluation parameters (adjusted RR = 2.60, 95% CI 1.45 to 4.67, p = 0.001), and from time-related changes in the other hemodynamic parameters (p < or = 0.033). CONCLUSIONS: PH retains independent prognostic significance even after adjusting for a large set of clinical/laboratory/instrumental parameters. Furthermore, serial measurements of mPAP seem to provide additional prognostic information as compared with a single assessment. These findings indicate that serial evaluations of PAP may help identify a sub-set of high-risk CHF patients deserving a particularly close follow-up to facilitate timely indications for non-pharmacologic strategies, including (when appropriate) heart transplantation.

Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy.

OBJECTIVES: We investigated the diagnostic accuracy of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy for differentiation of monoclonal immunoglobulin light-chain (AL) and transthyretin (TTR)-related cardiac amyloidosis. BACKGROUND: Differential diagnosis between TTR-related and AL amyloidosis is often complex and time-consuming. METHODS: Patients under routine observation with TTR-related/AL systemic amyloidosis and echocardiographic evidence of cardiac involvement were studied with 99mTc-DPD scintigraphy. RESULTS: Patients with cardiac involvement of TTR-related (group A; n = 15) and AL (group B; n = 10) etiology were comparable for left ventricular mass and renal function. Heart and heart/whole-body tracer retention were significantly higher (p < 0.05) in group A as compared with group B and with 10 unaffected controls. At visual scoring, cardiac 99mTc-DPD uptake was present in all group A patients and absent in all group B patients; thus, using genotyping/immunohistochemistry as the reference technique, the accuracy of 99mTc-DPD scintigraphy for distinction of TTR-related and AL etiology was 100%. Cardiac 99mTc-DPD uptake was also absent among unaffected controls. Using echocardiography as the reference standard for recognition of cardiac involvement, sensitivity and specificity of scintigraphy were both 100% for group A patients; in group B, sensitivity was 0% and specificity was 100% (accuracy, 50%). Eleven patients with myocardial 99mTc-DPD uptake underwent 99mTc-methylene diphosphonate (99mTc-MDP) scintigraphy; all patients showed a 99mTc-MDP myocardial visual score of 0. CONCLUSIONS: Etiology is a third major cause--in addition to type of organ-involved (soft-tissue/heart) and tracer type--of scintigraphic variability in cardiac amyloidosis. This is a highly relevant consideration for future studies. We conclude that 99mTc-DPD scintigraphy is a useful step in the workup of the differential diagnosis of TTR versus AL etiology in patients with documented cardiac amyloidosis.