Heroin Use Is Associated With Vascular Inflammation in Human Immunodeficiency Virus.

BACKGROUND: Heroin use may work synergistically with human immunodeficiency virus (HIV) infection to cause greater immune dysregulation than either factor alone. Unraveling how this affects end-organ disease is key as it may play a role in the excess mortality seen in people with HIV (PWH) who use heroin despite access to care and antiretroviral therapy. METHODS: This is a prospectively enrolled, cross-sectional study of adults with and without HIV who use and do not use heroin using (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to compare tissue-specific inflammation including aortic (target-to-background ratio [TBR]), splenic, and bone marrow (standardized uptake value [SUV]). RESULTS: A total of 120 participants were enrolled. The unadjusted mean difference in aortic TBR was 0.43 between HIV-positive [HIV+] heroin+ and HIV+ heroin-negative [heroin-] (P = .02); however, among HIV-, aortic TBR was similar regardless of heroin-use status. Further, HIV-by-heroin-use status interaction was significant (P = .02), indicating that the relationship between heroin use and higher aortic TBR depended on HIV status. On the other hand, both HIV (1.54 vs 1.68; P = .04, unadjusted estimated means for HIV+ vs HIV-) and heroin use were associated with lower bone marrow SUV, although the effect of heroin depended on sex (heroin-use-by-sex interaction, P = .03). HIV-by-heroin-use interaction was not significant for splenic or bone marrow SUV. CONCLUSIONS: Aortic inflammation was greatest in PWH who use heroin, but paradoxically, bone marrow activity was the least in this group, suggesting complex and possibly divergent pathophysiology within these different end organs.

Case series of closure devices complications.

Vascular closure devices (VCD) are effective at achieving hemostasis. VCD failure is attributed to underlying arterial disease, leading to a hazardous situation for obtaining contralateral femoral access. Radial-to-peripheral (R2P) access has emerged as a safe option to rescue these procedural complications. Here, we present two cases of VCD failure rescue utilizing R2P and outline this approach step-by-step.

Proportionate Cardiovascular Mortality in Chronic Inflammatory Disease in Adults in the United States From 1999 to 2019.

BACKGROUND: Despite a rising prevalence of chronic inflammatory disease (CID), the recent trends in cardiovascular disease (CVD) mortality of patients with CID is scarce. In this study, we investigated patterns of CVD mortality in systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) compared with the general population. METHODS: We used the 1999 to 2019 multiple causes of death files from the national center for health statistics to analyze patterns and trends of proportionate CVD mortality in CID compared with the general population. RESULTS: We analyzed a total of 11,154 CVD deaths in IBD, 58,337 CVD deaths in RA, 6227 CVD deaths in SLE, and 17,826,871 CVD deaths in the general population. Between 1999 and 2019, we found that proportionate CVD mortality decreased significantly in the IBD group (25% to 16%), RA group (34% to 25%), and the general population (41% to 31%), but did not change for the SLE group (15% to 15%). Patients with SLE who died of CVD were approximately 10 years younger compared with CVD decedents with RA, IBD, or general population. The White population had higher proportionate CVD mortality than African American (IBD [19% vs 16%-18%] and SLE [14%-16% vs 12-14%], respectively). CONCLUSIONS: This study identifies current trends in CVD mortality in the CID population and elucidates current demographics in CVD mortality in CID. Although proportionate CVD mortality decreased in the general population, and in patients with RA and IBD, there was no change among patients with SLE. Further studies are needed to elucidate these differences.

The three faces of takotsubo cardiomyopathy in a single patient.

While the classical apical ballooning takotsubo cardiomyopathy (TC) was first reported in the 1990s, the rarer mid-ventricular and basal variants were not formally recognized until recently and they remain poorly understood. In this case report, we describe a 67-year-old woman who, during her hospitalization for a subarachnoid hemorrhage and subsequent readmission, experienced multiple complications, each of which resulted in a different variant of TC. To our knowledge, this is the first report of a single patient developing all three variants of TC.

Contrast-enhanced echocardiographic detection of severe aortic insufficiency in venoarterial extracorporeal membrane oxygenation.

Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support is an increasingly used temporizing therapy for patients with refractory cardiogenic shock. Contrast-enhanced echocardiography plays a critical role in the diagnosis and management of diseases that precipitate severe cardiac failure. In this case report, we describe a previously healthy 60-year-old woman who presented with dyspnea on exertion, and whose hospital course was complicated by ventricular fibrillation, emergent coronary artery bypass surgery (CABG), and ECMO support. Her contrast-enhanced ECMO images demonstrated a unique pattern of opacification of three of the four cardiac chambers, which led to a diagnosis of severe aortic insufficiency.

Inhalation injury severity and systemic immune perturbations in burned adults.

OBJECTIVE: We aimed to determine whether the severity of inhalation injury evokes an immune response measurable at the systemic level and to further characterize the balance of systemic pro- and anti-inflammation early after burn and inhalation injury. BACKGROUND: Previously, we reported that the pulmonary inflammatory response is enhanced with worse grades of inhalation injury and that those who die of injuries have a blunted pulmonary immune profile compared with survivors. METHODS: From August 2007 to June 2011, bronchoscopy was performed on 80 patients admitted to the burn intensive care unit when smoke inhalation was suspected. Of these, inhalation injury was graded into 1 of 5 categories (0, 1, 2, 3, and 4), with grade 0 being the absence of visible injury and grade 4 corresponding to massive injury. Plasma was collected at the time of bronchoscopy and analyzed for 28 immunomodulating proteins via multiplex bead array or enzyme-linked immunosorbent assay. RESULTS: The concentrations of several plasma immune mediators were increased with worse inhalation injury severity, even after adjusting for age and % total body surface area (TBSA) burn. These included interleukin (IL)-1RA (P = 0.002), IL-6 (P = 0.002), IL-8 (P = 0.026), granulocyte colony-stimulating factor (P = 0.002), and monocyte chemotactic protein 1 (P = 0.007). Differences in plasma immune mediator concentrations in surviving and deceased patients were also identified. Briefly, plasma concentrations of IL-1RA, IL-6, IL-8, IL-15, eotaxin, and monocyte chemotactic protein 1 were higher in deceased patients than in survivors (P < 0.05 for all), whereas IL-4 and IL-7 were lower (P < 0.05). After adjusting for the effects of age, % TBSA burn, and inhalation injury grade, plasma IL-1RA remained significantly associated with mortality (odds ratio, 3.12; 95% confidence interval, 1.03-9.44). Plasma IL-1RA also correlated with % TBSA burn, inhalation injury grade, fluid resuscitation, Baux score, revised Baux score, Denver score, and the Sequential Organ Failure Assessment score. CONCLUSIONS: The severity of smoke inhalation injury has systemically reaching effects, which argue in favor of treating inhalation injury in a graded manner. In addition, several plasma immune mediators measured early after injury were associated with mortality. Of these, IL-1RA seemed to have the strongest correlation with injury severity and outcomes measures, which may explain the blunted pulmonary immune response we previously found in nonsurvivors.

Ruptured mycotic coronary artery aneurysm.

Aneurysms complicated by rupture of the coronary arteries are exceedingly rare. Literature regarding management of mycotic aneurysms resulting in rupture is limited. Therefore, we describe a fascinating diagnosis, imaging progression and management of a ruptured mycotic coronary artery aneurysm.

Geographical Patterns and Risk Factor Association of Cardio-Oncology Mortality in the United States.

Cardio-oncology mortality (COM) is a complex issue that is compounded by multiple factors that transcend a depth of socioeconomic, demographic, and environmental exposures. Although metrics and indexes of vulnerability have been associated with COM, advanced methods are required to account for the intricate intertwining of associations. This cross-sectional study utilized a novel approach that combined machine learning and epidemiology to identify high-risk sociodemographic and environmental factors linked to COM in United States counties. The study consisted of 987,009 decedents from 2,717 counties, and the Classification and Regression Trees model identified 9 county socio-environmental clusters that were closely associated with COM, with a 64.1% relative increase across the spectrum. The most important variables that emerged from this study were teen birth, pre-1960 housing (lead paint indicator), area deprivation index, median household income, number of hospitals, and exposure to particulate matter air pollution. In conclusion, this study provides novel insights into the socio-environmental drivers of COM and highlights the importance of utilizing machine learning approaches to identify high-risk populations and inform targeted interventions for reducing disparities in COM.

Myocardial Injury and the Risk of Stroke in Patients With Chronic Kidney Disease (From the Chronic Renal Insufficiency Cohort Study).

Patients with chronic kidney disease (CKD) are at increased risk for stroke. High-sensitivity troponin (hsTP), a marker of myocardial injury, has been associated with stroke risk in patients without CKD, but whether this applies to patients with CKD is not known. We assessed whether hsTP levels is associated with incident stroke in patients with mild-to-moderate CKD without a history of stroke enrolled in the Chronic Renal Insufficiency Cohort. Patients were followed for incident stroke, and the association with hsTP was assessed. A total of 3477 patients without prior stroke were included in this investigation. Over a median follow-up of 7.3 years, 101 (2.8%) patients had an incident stroke. Baseline hsTP was associated with a 9-year risk of stroke (quartile 1: 1.8%, quartile 2: 3.8%, quartile 3: 4.9%, quartile 4: 7.3%; P < .001). After adjusting for traditional stroke risk factors, patients in the fourth quartile (hazard ratio: 2.52, 95% CI: 1.10-5.76, P = .021) had higher risk of stroke when compared with the lowest quartile of hsTP. In conclusion, hsTP levels are associated with increased risk of incident stroke in patients with mild to moderate CKD, and this association remains significant despite the adjustment for traditional risk factors and CKD.

Examining Disparities and Excess Cardiovascular Mortality Before and During the COVID-19 Pandemic.

OBJECTIVE: To investigate the patterns and demographic features of cardiovascular disease (CVD) death and subtypes myocardial infarction (MI), stroke, and heart failure in the pre-COVID-19 era (2018-2019) vs during the COVID-19 pandemic (2020-2021) in the United States. METHODS: In this cross-sectional study, we used the US Multiple Cause of Death files for 2018 to 2021 to examine the trend of excess cause-specific deaths using International Classification of Diseases, Tenth Revision codes for CVD (I00 to I99), MI (I21 and I22), stroke (I60 to I69), and heart failure (I42 and I50). Our primary outcome was excess mortality from CVD and its 3 subtypes (MI, stroke, and heart failure) between prepandemic (2018-2019) and pandemic (2020-2021) years. We performed a subgroup analysis on race and month-to-month and year-to-year variation using χ2 analysis to test statistical significance. RESULTS: Overall, 3,598,352 CVD deaths were analyzed during the study period. There was a 6.7% excess CVD mortality, 2.5% MI mortality, and 8.5% stroke mortality during the COVID-19 pandemic (2020-2021) compared with the prepandemic era (2018-2019). Black individuals had higher excess CVD mortality (13.8%) than White individuals (5.1%; P<.001). This remained consistent across subtypes of CVD, including MI (9.6% vs 1.0%; P<.001), stroke (14.5% vs 6.9%; P<.001), and heart failure (5.1% vs -1.2%; P<.001). CONCLUSION: There has been a significant rise in CVD and subtype-specific mortality during the COVID-19 pandemic that has been persistent despite 2 years since the onset of the pandemic. Excess CVD mortality has disproportionately affected Black compared with White individuals. Further studies targeting and eliminating health care disparities are necessary.

Inflammation-mediated vitamin K and vitamin D effects on vascular calcifications in people with HIV on active antiretroviral therapy.

BACKGROUND: People with HIV (PWH) experience increased systemic inflammation and monocyte activation, leading to increased risk of cardiovascular events (death, stroke, and myocardial infarction) and higher coronary artery calcium scores (CACs). Vitamins D and K2 have significant anti-inflammatory effects; in addition, vitamin K2 is involved in preventing vascular calcifications in the general population. The roles of vitamins D and K in increased coronary calcifications in successfully treated PWH is less understood. METHODS: We prospectively recruited 237 PWH on antiretroviral treatment (ART) and 67 healthy controls. CACs were derived from noncontrast chest computed tomography (CT) and levels of 25-hydroxyvitamin D (vitamin D) and inactive vitamin K-dependent dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP, marker of vitamin K deficiency) were measured in plasma during a fasting state. The relationship between inflammation markers, dp-uc MGP, and vitamin D on CACs were estimated using zero-inflated negative binomial regression. Adjusted models included 25(OH)D, MGP, sex, race, age, and markers of inflammation or monocyte activation. RESULTS: Overall, controls had lower median age (45.8 vs. 48.8; P = 0.03), a larger proportion of female individuals (55.2 vs. 23.6%; P < 0.0001), and nonwhite (33.8 vs. 70%; P < 0.0001). Among PWH, less than 1% had detectable viral load and the median CD4+ cell count was 682 (IQR: 473.00-899.00). 62.17% of the participants had zero CACs and 51.32% were vitamin D-deficient (<20 ng/ml). There was no difference in detectable CACs (P = 0.19) or dp-uc MGP (P = 0.42) between PWH and controls. In adjusted models, PWH with nonzero CACs have three times greater expected CAC burden compared with controls. Every 1% increase in MGP (worse K status) decreases the probability of having CACs equal to zero by 21.33% (P = 0.01). Evidence suggests that the effects of 25(OH)D and MGP are inflammation-mediated, specifically through sVCAM, TNF-αRI, and TNF-αRII. CONCLUSION: Vitamin K deficiency is a modifiable preventive factor against coronary calcification in PWH. Further research should determine whether vitamin K supplementation would reduce systemic inflammation, vascular calcification, and risk of cardiovascular events in PWH.

Myeloperoxidase is Independently Associated with Incident Heart Failure in Patients with Coronary Artery Disease and Kidney Disease.

Chronic kidney disease (CKD) is associated with high cardiovascular risk and mortality. Myeloperoxidase (MPO) has been linked to adverse events in patients with mild-moderate CKD. We sought to investigate whether MPO levels are associated with adverse outcomes in patients with CKD. We studied participants with mild to moderate CKD in the prospective chronic renal insufficiency cohort (CRIC). We followed patients for incident heart failure (HF), death, and composite outcome (myocardial infarction, incident peripheral arterial disease, cerebrovascular accident and death). A total of 3872 patients were included (2702 without CVD, 1170 with CVD). After multiple adjustments, doubling of MPO in patients with prior CAD was associated with risk of HF (HR 1.15 [1.01-1.30], P = 0.032) and mortality (HR 1.16 [1.05-1.30], P = 0.005), and composite outcome of MI, PAD, CVA and death (HR 1.12 [1.01-1.25], P = 0.031). In this cohort of patients with mild to moderate CKD and CAD, MPO levels are independently associated with incident HF, all-cause mortality, and a composite outcome.

Inflammatory Markers and Risk of Heart Failure With Reduced to Preserved Ejection Fraction.

Chronic systemic inflammation is associated with an increased risk of heart failure (HF). We sought to determine the association between biomarkers of systemic inflammation interleukin (IL)-6, IL-2, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) with those of HF and its subtypes. We hypothesize that inflammatory biomarkers IL-6, IL-2, TNF-α, and CRP are associated with HF and its subtypes. We included participants from the Multi-Ethnic Study of Atherosclerosis (a prospective population-based cohort study [2000 to 2002]), without a history of HF, and with available baseline inflammatory biomarkers. We explored the association of IL-6, IL-2, TNF-α, and CRP with incident HF, HF with reduced ejection fraction (left ventricular ejection fraction [LVEF] <40%, HFrEF), HF with midrange EF (LVEF 40% to 50%, HFmrEF), and HF with preserved ejection fraction (LVEF >50%, HFpEF). Among 6,814 participants, 195 developed HF over 10.9 years (56 HFrEF, 30 HFmrEF, and 57 HFpEF). In the models adjusted for clinical risk factors of HF, IL-6 (hazard ratio [HR] 1.33 per doubling; 95% confidence interval [CI] 1.10 to 1.60), TNF-α (HR 2.49 per doubling; 95% CI 1.18 to 5.28), and CRP (HR 1.18 per doubling; 95% CI 1.06 to 1.30) were associated with all HF, and IL-6 (HR 1.51 per doubling; 95% CI 1.09 to 2.10) and CRP (HR 1.21 per doubling; 95% CI: 1.01 to 1.45) were associated with incident HFpEF, whereas none of the examined biomarkers were associated with HFmrEF or HFrEF. In conclusion, inflammatory biomarkers (IL-6, TNF-α, and CRP) are independently associated with incident HF. IL-6 and CRP are associated with incident HFpEF but not HFrEF or HFmrEF. These findings suggest that activation of the IL-6/CRP pathway (as cause, consequence, or epiphenomenon) may be unique to HFpEF.

Multi-variable biomarker approach in identifying incident heart failure in chronic kidney disease: results from the Chronic Renal Insufficiency Cohort study.

AIMS: Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality in the ever-growing population of patients with chronic kidney disease (CKD). There is a need to enhance early prediction to initiate treatment in CKD. We sought to study the feasibility of a multi-variable biomarker approach to predict incident HF risk in CKD. METHODS AND RESULTS: We examined 3182 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) without prevalent HF who underwent serum/plasma assays for 11 blood biomarkers at baseline visit (B-type natriuretic peptide [BNP], CXC motif chemokine ligand 12, fibrinogen, fractalkine, high-sensitivity C-reactive protein, myeloperoxidase, high-sensitivity troponin T (hsTnT), fibroblast growth factor 23 [FGF23], neutrophil gelatinase-associated lipocalin, fetuin A, aldosterone). The population was randomly divided into derivation (n = 1629) and validation (n = 1553) cohorts. Biomarkers that were associated with HF after adjustment for established HF risk factors were combined into an overall biomarker score (number of biomarkers above the Youden's index cut-off value). Cox regression was used to explore the predictive role of a biomarker panel to predict incident HF. A total of 411 patients developed incident HF at a median follow-up of 7 years. In the derivation cohort, four biomarkers were associated with HF (BNP, FGF23, fibrinogen, hsTnT). In a model combining all four biomarkers, BNP (hazard ratio [HR] 2.96 [95% confidence interval 2.14-4.09]), FGF23 (HR 1.74 [1.30-2.32]), fibrinogen (HR 2.40 [1.74-3.30]), and hsTnT (HR 2.89 [2.06-4.04]) were associated with incident HF. The incidence of HF increased with the biomarker score, to a similar degree in both derivation and validation cohorts: from 2.0% in score of 0% to 46.6% in score of 4 in the derivation cohort to 2.4% in score of 0% to 43.5% in score of 4 in the validation cohort. A model incorporating biomarkers in addition to clinical factors reclassified risk in 601 (19%) participants (352 [11%] participants to higher risk and 249 [8%] to lower risk) compared with clinical risk model alone (net reclassification improvement of 0.16). CONCLUSION: A basic panel of four blood biomarkers (BNP, FGF23, fibrinogen, and hsTnT) can be used as a standalone score to predict incident HF in patients with CKD allowing early identification of patients at high-risk for HF. Addition of biomarker score to clinical risk model modestly reclassifies HF risk and slightly improves discrimination.

Prevalence of thoracic aortic aneurysm in patients referred for no/low-charge coronary artery calcium scoring: Insights from the CLARIFY registry.

Objective: Low-dose cardiac-gated chest CTs allow for simultaneous evaluation of coronary artery calcification and aortic size. We sought to evaluate the prevalence of thoracic aortic dilation (TAD) and thoracic aortic aneurysm (TAA) in a large cohort of patients undergoing coronary artery calcium (CAC) screening. Methods: We reviewed all patients from a large, prospective no-charge CAC screening program (CLARIFY, Clinicaltrials.gov NCT04075162) for whom measurements of the ascending aorta were available. TAD was defined as an ascending aortic diameter ≥4.0cm, while TAA was defined as ascending aortic diameter ≥ 4.5cm. We explored associations between patient characteristics, CAC, and the prevalence of TAD/TAA. Results: A total of 36,356 patients enrolled in the CLARIFY program underwent analysis for TAD/TAA. 3,130 patients (8.6%) had TAD and 237 (0.7%) had TAA. Patients with TAA were older (63±8 vs 59±10 years, p < 0.001), more likely to be male (87% vs 49%, p < 0.001), have higher BMI (32 vs 30 kg/m2, p < 0.001), and 10-year atherosclerotic cardiovascular disease estimated risk (18% vs 12%, p < 0.001). Similar differences were observed for individuals with TAD compared to individuals without TAD with respect to age (63 vs 59 years, p < 0.001), percent male (76% vs 46%, p < 0.001), BMI (32 vs 30 kg/m2, p < 0.001), and 10-year predicted risk (17% vs 11%, p < 0.001). CAC score was associated with prevalence of TAD (4.9% in those with CAC 0 to 16.5% in those with CAC≥400) and TAA (0.3% in those with CAC of 0 to 1.5% in those with CAC ≥400). Conclusion: In this large, prospective study of patients undergoing no-charge CAC screening, 8.6% had TAD (≥4.0cm) and 0.7% had TAA (≥4.5cm). Our results highlight a high yield of TAD/TAA diagnosis in this targeted cohort with cardiovascular risk factors and supports the role of no-charge CAC as a population-level strategy.

Proportionate and Absolute Vascular Disease Mortality by Race and Sex in the United States From 1999 to 2019.

Background Despite the known significant morbidity and mortality associated with cardiovascular disease and peripheral vascular disease (PVD), contemporary data describing racial demographics in PVD mortality are scarce. Methods and Results Using the multiple causes of death file from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research, we analyzed the trends of age-adjusted mortality (AAMR) for PVD and its subtypes (aortic aneurysm/dissection, arterial thrombosis, venous thrombosis/disease, pulmonary embolism), by race and sex between 1999 and 2019. Of the 17 826 871 deaths attributed to cardiovascular disease, a total of 888 187 (5.0%) PVD deaths were analyzed during the study period (12.4% Black, 85.6% White). Between 1999 and 2019, AAMR for PVD decreased by 52% (24.8-11.8 per 100 000 people) in the overall population. Despite a decrease in the overall mortality across all race and sex groups, Black men and Black women continued to have higher mortality for PVD (1.5×), aortic dissection (1.8×), arterial thrombosis (1.3×), and venous thrombosis/disease (2.0×) mortality compared with White men and White women in 2019. While there was a 53% decrease in PVD among White individuals (AAMR 24.5-11.5 per 100 000), there was only a 43% decrease (30.0-17.1) in PVD AAMR in Black individuals between 1999 and 2019. The ratio of PVD AAMR increased from 1.2 (1999) to 1.5 (2019) in Black men/White men and from to 1.3 (1999) to 1.5 (2019) in Black women/White women. Similar trends were noted in aortic dissection (Black men/White men, 1.2-1.8; and Black women/White women, 1.5-1.7), arterial thrombosis (Black men/White men, 1.0-1.3; and Black women/White women, 0.9-1.3), and venous thrombosis/disease (Black men/White men, 1.7-1.8; and Black women/White women, 1.7-2.0). Conclusions In this retrospective review of death certificate data in the United States, we demonstrate continued significant disparities between Black and White populations in PVD mortality and its subtypes. Future studies should investigate etiologies and social determinants of PVD mortality.

Non-invasive Imaging in the Evaluation of Cardiac Allograft Vasculopathy in Heart Transplantation: A Systematic Review.

Cardiac allograft vasculopathy (CAV) is the leading cause of long-term graft dysfunction in patients with heart transplantation and is linked with significant morbidity and mortality. Currently, the gold standard for diagnosing CAV is coronary imaging with intravascular ultrasound during traditional invasive coronary angiography. Invasive imaging, however, carries increased procedural risk and expense to patients in addition to requiring an experienced interventionalist. With the improvements in non-invasive cardiac imaging modalities such as transthoracic echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography, an alternative non-invasive imaging approach for the early detection of CAV may be feasible. In this systematic review, we explored the literature to investigate the utility of non-invasive imaging in diagnosis of CAV in >3000 patients across 49 studies. We also discuss the strengths and weaknesses for each imaging modality. Overall, all 4 imaging modalities show good to excellent accuracy for identifying CAV with significant variations across studies. Majority of the studies compared non-invasive imaging with invasive coronary angiography without intravascular imaging. In summary, non-invasive imaging modalities offer an alternative approach to invasive coronary imaging for CAV. Future studies should investigate longitudinal non-invasive protocols in low-risk patients after heart transplantation.