Clinical and genetic predictors of cardiac dysfunction assessed by echocardiography in patients with hereditary hemochromatosis.

PURPOSE: Hereditary hemochromatosis (HH) may cause iron deposition in cardiac tissue. We aimed to describe the echocardiographic findings in patients with HH and identify risk factors for cardiac dysfunction. METHODS: In this retrospective study, we included patients with HH who underwent transthoracic echocardiography at our tertiary care center between August 2000 and July 2022. We defined three primary outcomes for cardiac dysfunction: 1) left ventricular ejection fraction (LVEF) < 55%, 2) ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') > 15, and 3) global longitudinal strain (GLS) < 18. Multivariable logistic regression was utilized to identify predictors of cardiac dysfunction. RESULTS: 582 patients (median age 57 years, 61.2% male) were included. The frequency of LVEF < 55%, E/e' > 15 and GLS < 18 was 9.0% (52/580), 9.6% (51/534) and 20.2% (25/124), respectively. In multivariable analysis, non-White race, age, and hypertension were associated with E/e' > 15. No specific HFE genetic mutation was associated with LVEF < 55%. A history of myocardial infarction was strongly associated with both LVEF < 55% and E/e' > 15. In patients with LVEF ≥ 55%, the C282Y/H63D genetic mutation was associated with reduced likelihood of E/e' > 15, p = 0.024. Patients with C282Y/H63D had a higher frequency of myocardial infarction. Smoking and alcohol use were significantly associated with GLS < 18 in unadjusted analysis. CONCLUSION: We found the traditional risk factors of male sex, and history of myocardial infarction or heart failure, were associated with a reduced LVEF, irrespective of the underlying HFE genetic mutation. Patients with a C282Y/H63D genetic mutation had a higher frequency of myocardial infarction, yet this mutation was associated with reduced odds of diastolic dysfunction compared to other genetic mutations in patients with a normal LVEF.

Appropriately testing patients with intermediate risk for coronary artery disease: how well are we doing?

BACKGROUND: Cardiovascular risk assessment and stratification of stable coronary artery disease represents a pivotal component of coronary artery disease management. The introduction of risk stratification tools has advanced the detection of patients with intermediate to high risk for coronary artery events. These patients will ultimately undergo non-invasive and invasive cardiovascular testing. OBJECTIVE: To synthesise evidence illustrating risk stratification tools and non-invasive testing for patients with intermediate risk for coronary artery disease and suggest a simple method for clinicians to follow prior to ordering non-invasive cardiovascular testing. STUDY SELECTION: Literature review of PubMed and MEDLINE Central on studies and evidence highlighting the appropriate use criteria for radionuclide myocardial perfusion imaging. FINDINGS AND CONCLUSIONS: Overtestingusing myocardial perfusion imaging is well documented in several studies in the literature. Few studies highlighted the importance of the appropriate use criteria for radionuclide myocardial perfusion imaging, which can reduce unnecessary testing in patients with suspected coronary artery disease. Herein, we propose 'Simple Steps to Follow' to be considered by clinicians prior to ordering radionuclide myocardial perfusion imaging. The target audience of this article is internal and family medicine primary care physicians and other non-cardiologist physicians.

Coronary Interventions before Liver Transplantation Might Not Avert Postoperative Cardiovascular Events.

Percutaneous coronary intervention and coronary artery bypass grafting may be performed before orthotopic liver transplantation (OLT) to try to improve the condition of patients who have severe ischemic heart disease. However, data supporting improved outcomes are lacking. We reviewed the medical records of 2,010 patients who underwent OLT at our hospital from 2000 through 2010. The 51 patients who underwent coronary artery angiography within 6 months of transplantation were included in this study: 28 had mild coronary artery disease, 10 had moderate disease, and 13 had severe disease. We compared all-cause and cardiac-cause mortality rates. We found a significant difference in cardiac deaths between the groups (P <0.001), but none in all-cause death (P=0.624). Of the 10 patients who had moderate coronary artery disease, one underwent pre-transplant coronary artery bypass grafting. Of 13 patients with severe disease, 3 underwent percutaneous coronary intervention, and 6 underwent coronary artery bypass grafting. Overall, 50% of patients who underwent either intervention died of cardiac-related causes, whereas no patient died of a cardiac-related cause after undergoing neither intervention (P <0.0001). We conclude that, despite coronary intervention, mortality rates remain high in OLT patients who have severe coronary artery disease.

Use of a melody pulmonary valve in transcatheter valve-in-valve replacement for tricuspid valve bioprosthesis degeneration.

Bioprosthetic heart valves can degenerate and fail over time. Repeat surgery as a means of replacement increases morbidity and mortality rates, and some patients are not candidates for reoperation. A newer treatment, percutaneous transcatheter valve-in-valve implantation, might delay or substitute for invasive procedures. We present the case of a 51-year-old woman, a poor candidate for surgery who had prosthetic tricuspid valve degeneration and stenosis. We successfully performed valve-in-valve placement of a Melody(®) valve, using a procedure originally intended to treat pulmonary valve conduit obstruction or regurgitation. To our knowledge, this is among the first case reports to describe the use of the Melody pulmonary valve in transcatheter valve-in-valve replacement for prosthetic tricuspid stenosis that was otherwise not correctable. Additional data and longer follow-up periods are necessary to gain an understanding of ideal indications and selection of patients for the percutaneous transcatheter treatment of tricuspid valve stenosis.

Radiation dose in cardiac imaging: how should it affect clinical decisions?

OBJECTIVE: The purpose of this article is to discuss whether and how the risks of exposure to ionizing radiation should affect clinical decision making in patients with known or suspected cardiovascular disease. CONCLUSION: Although the prevalence of cardiovascular disease and frequency of diagnostic testing has risen dramatically, cardiovascular mortality has declined. Earlier and more accurate detection of cardiovascular disease may play an important role. Concerns regarding excessive radiation exposure from cardiovascular imaging have been raised. Efforts to reduce exposure have included selection of appropriate patients for cardiovascular testing, technologic advances, educational resources, and a directed patient-centered approach to testing.

Diffuse diseases of the myocardium: MRI-pathologic review of nondilated cardiomyopathies.

OBJECTIVE: This article will present correlation of the key radiologic findings with gross and microscopic pathology for the characterization of diffuse myocardial diseases using advanced imaging techniques. Our goal is to provide a focused and in-depth review of the pathophysiology underlying each entity and to emphasize the structural basis for the corresponding imaging characteristics. This article is limited to those disorders characterized by ventricular wall thickening without chamber dilatation, including hypertrophic cardiomyopathy, hypertensive cardiomyopathy, and cardiac amyloidosis. CONCLUSION: For the characterization of diffuse myocardial diseases using advanced imaging techniques, it is essential to understand the underlying pathologic changes in the heart. With these techniques, such as cardiac MRI, the various cardiomyopathies can be differentiated accurately, which may potentially obviate invasive testing and endomyocardial biopsy.

A heart of stone: a case of acute development of cardiac calcification and hemodynamic collapse.

Acute cardiac calcification is a clinical entity that may develop over days to months and is usually localized to areas of healed myocardial infarction, cardiac surgery or trauma. We present an unusual case of rapidly developing non-ischemic cardiac calcification in the setting of sepsis and end stage renal disease resulting in acute diastolic dysfunction and cardiac collapse diagnosed by computed tomography (CT) and confirmed by autopsy. We propose that dedicated cardiac CT may provide the most accurate means to detect cardiac calcification.

Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from the Biomarkers of Aortic Stenosis Severity [BASS] study).

We correlated von Willebrand factor (VWF) activity indexes and brain natriuretic peptide (BNP) with measures of aortic stenosis (AS) severity, bleeding, symptoms, and freedom from death or aortic valve replacement. Patients with AS (n = 66 [16 mild, 20 moderate, and 30 severe]) and aortic valve replacement (n = 21) were assessed with VWF antigen, VWF latex agglutination immunoturbidic activity, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer ratio, and BNP level after echocardiography. In patients with AS, the mean gradient correlated with BNP (Spearman r = 0.29, p = 0.02), VWF latex agglutination immunoturbidic activity/VWF antigen ratio (r = -0.41, p <0.001), PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). The area under the curve for detection of severe AS was 0.62 (95% confidence interval [CI] 0.48 to 0.77) by elevated BNP, 0.81 (95% CI 0.69 to 0.92) by PFA-CADP closure time, 0.69 (95% CI 0.55 to 0.82) by VWF latex agglutination immunoturbidic activity/VWF antigen ratio, and 0.86 (95% CI 0.76 to 0.95) by VWF multimer ratio. For the VWF multimer ratio, a threshold of 0.15 yielded a sensitivity and specificity for severe AS of 77% and positive predictive value of 74%. Bleeding (in 14%) was associated with a prolonged PFA-CADP time and reduced VWF latex agglutination immunoturbidic activity/VWF antigen ratio. Symptoms were associated with elevated BNP and low Duke Activity Status Index score. In 66 patients with AS, freedom from death (n = 4) or aortic valve replacement (n = 22) was associated with PFA-CADP (p = 0.003), VWF high-molecular-weight multimers (p = 0.009), and VWF latex agglutination immunoturbidic activity/VWF antigen ratio (p <0.001) but not BNP (p = 0.32). In severe AS versus aortic valve replacement, the PFA-CADP and VWF multimer ratio differed (p <0.001), but BNP and the VWF latex agglutination immunoturbidic activity/VWF antigen ratio did not. In conclusion, the VWF activity indexes were associated with AS severity and bleeding and were predictive of cardiovascular outcomes.

Regulation of circulating progenitor cells in left ventricular dysfunction.

BACKGROUND: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. METHODS AND RESULTS: A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. CONCLUSIONS: This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers.

Radiation dose reduction in CT coronary angiography.

During recent years, technologic advancements in computed tomography (CT) have allowed robust cardiac and coronary imaging. Small, mobile cardiac structures such as the coronary arteries can now be imaged directly and noninvasively with high precision. Given the fact that coronary CT angiography (CCTA) can detect preclinical calcified and noncalcified atherosclerosis, there is potential to revolutionize the management of ischemic heart disease by refining risk stratification and improving outcomes in various clinical settings. However, despite this progress, CT has come under scrutiny as concerns about the level and risk of the radiation exposure of the population grow. Although there are no data to support a direct association between CT imaging and risk of future cancer, health care practitioners should make every effort to minimize radiation exposure to their patients. The purpose of this article is to describe techniques that can reduce radiation dose to patients during CCTA but maintain diagnostic image quality.