Hepatitis C and heart transplantation: An update.

There are limited data regarding heart transplantation in the setting of hepatitis C virus (HCV) infection in either recipients or donors, as the practice was infrequent, given concerns of worse post-transplant outcomes. This changed dramatically after the development of highly effective HCV therapies, namely direct-acting antivirals (DAAs). Additionally, nucleic acid testing currently in use establishes more precisely the risk of HCV transmission from donors. As a result, chronic HCV infection in itself is no longer a barrier for heart transplant candidates, and the use of HCV-positive organs for HCV-infected and non-infected transplant candidates has increased dramatically. A review of the literature revealed that in the pre-DAA era, HCV seropositive heart transplant patients had a higher mortality than their seronegative counterparts. However, short-term data suggest that the differences in survival have been erased in the DAA era. Heart transplantation from HCV-viremic donors to HCV-uninfected recipients has become increasingly common as the number of deceased donors with HCV viremia has increased over the past years. Preliminary outcome reports are very encouraging, although further data are needed with regard to long-term safety. New information continues to be incorporated to optimize protocols that guide this practice.

Prognostic significance of blood pressure response during vasodilator stress Rb-82 positron emission tomography myocardial perfusion imaging.

BACKGROUND: A drop in blood pressure (BP) or blunted BP response is an established high-risk marker during exercise myocardial perfusion imaging (MPI); however, data are sparse regarding the prognostic value of BP response in patients undergoing vasodilator stress rubidium-82 (Rb-82) Positron Emission Tomography (PET) MPI. METHODS AND RESULTS: From the PET Prognosis Multicenter Registry, a cohort of 3413 patients underwent vasodilator stress Rb-82 PET MPI with dipyridamole or adenosine. We used multivariable Cox proportional hazard regression to analyze the association with mortality of four BP variables: stress minus rest systolic BP (∆SBP), stress minus rest diastolic BP (∆DBP), resting systolic BP (rSBP), and resting diastolic BP (rDBP). Covariates that had univariate P values <.10 were entered into the multivariable model. After median 1.7 years follow-up, 270 patients died. In univariate analyses, ∆SBP (P = .082), rSBP (P = .008), and rDBP (P < .001) were of potential prognostic value (P < .10), but ∆DBP was not (P = .96). After adjustment for other clinical and MPI variables, ∆SBP no longer independently predicted mortality (P = .082); only lower rSBP (P = .026) and lower rDBP (P = .045) remained independently prognostic. CONCLUSIONS: In patients undergoing vasodilator stress MPI, only lower resting BP is an independent predictor of mortality along with other clinical and MPI variables; BP response does not appear to add to risk stratification in these patients.

Team-Based Care for Managing Cardiac Comorbidities in Heart Failure.

The need for HF management is predicted to increase as the HF population ages. Balancing HF and the multiple cardiac comorbidities remains difficult for any single provider, but becomes Fig. 6. Five-year rates of death or urgent heart transplantation by deciles of total cholesterol in heart failure. (From Horwich TB, Fonarow GC, Hamilton MA, et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002;8(4):222; with permission.) easier with the involvement of a team. Collaboration between physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other health care workers reduces the burden of care coordination and simultaneously improves delivery of care. Team-based approaches increase cost-effectiveness, reduce hospitalization rates, and equally important, give patients more resources and support, which research shows may ultimately improve compliance and outcomes.

Clinical Utility of Patient-Reported Outcome Instruments in the Management of Pulmonary Hypertension: A Systematic Review.

BACKGROUND: Despite the greater sensitivity and specificity of disease-specific patient-reported outcome measures (PROM) to detect clinical change, only recently have such instruments been developed for pulmonary hypertension (PH), specifically pulmonary arterial hypertension (PAH) and chronic thromboembolic disease (CTEPH). Although these valuable tools are now being incorporated into clinical studies of PH, they have not yet reached widespread integration into routine clinical care. OBJECTIVES: In this systematic review, the authors assess the psychometric properties of PROM developed for PH, compare PROM with other clinical outcomes in PH, and address the utility of PROM in clinical care. METHODS: The authors performed a systematic search of papers published between January 1, 2006, and October 1, 2022, using the MEDLINE database to identify PROM developed and validated for PH. The identified PROM were found to have been developed only in groups with PAH and CTEPH. The authors evaluated the identified instruments according to established psychometric criteria. An additional search was performed to identify randomized controlled trials (RCTs) utilizing these PROM for comparison with clinical outcomes. RESULTS: From 527 papers retrieved, a total of 35 PROM were identified. Of these, 5 disease-specific instruments were included in the final analysis. While both CAMPHOR (Cambridge Pulmonary Hypertension Outcome Review) and emPHasis-10 performed well in patients with PAH and CTEPH with regard to their psychometric properties, emPHasis-10 demonstrated superior feasibility for use in clinical practice due to its concise format. The Pulmonary Arterial Hypertension-Symptoms and Impacts Questionnaire performed well in the authors' analysis, though additional data is needed regarding interpretability and feasibility. CONCLUSIONS: EmPHasis-10 demonstrated strong psychometric properties and the greatest feasibility for clinical use. Further study assessing the integration of PROM into routine clinical care for PH is needed.

Trends in Consent for Clinical Trials in Cardiovascular Disease.

BACKGROUND: Cardiovascular clinical trials depend on patient enrollment. Enrollment rates appear inadequate, but little is known about how frequently patients accept or decline offers of enrollment. The objective of this study was to assess trends and predictors of patient acceptance of offers to enroll in clinical trials for cardiovascular disease. METHODS AND RESULTS: We utilized an established database containing all randomized, controlled trials (n=1224) in cardiovascular disease published between 2001 and 2012 in the 8 highest-impact general medical and cardiology journals. Studies were eligible if the number of patients approached and number of patients declining enrollment could be ascertained from published materials. All studies were screened for eligibility. Each eligible study was reviewed by 3 co-authors. All discrepancies were resolved by the group. The main outcome was acceptance rate, defined as the number of patients enrolled divided by the number patients who were eligible and approached. Only 21.7% (n=266) of studies provided information sufficient to assess patient enrollment and refusals. The median acceptance rate across trials was 83.2%. Significant predictors of higher enrollment included: enrollment in the acute setting (P=0.031); geographical region (P<0.001 for group); and trial sponsorship (P=0.006 for group). CONCLUSIONS: Rates of reporting data sufficient to calculate acceptance rates are low. This compromises the ability to identify drivers of low enrollment and assess trial generalizability. However, the high rates of acceptance observed suggest that factors other than patients' decisions may be the primary drivers of declining rates of trial enrollment.

Prognostic significance of (123)I-mIBG SPECT myocardial imaging in heart failure: differences between patients with ischaemic and non-ischaemic heart failure.

AIMS: The purpose of this study was to examine the prognostic significance of uptake patterns on quantitative myocardial (123)I-mIBG and (99m)Tc-tetrofosmin SPECT imaging in heart failure (HF) subjects and to assess the differences between patients with ischaemic and non-ischaemic HF. METHODS AND RESULTS: Results of quantitative analyses of (123)I-mIBG myocardial SPECT, alone and in combination with (99m)Tc tetrofosmin SPECT, were studied in 619 ischaemic (I) and 319 non-ischaemic (NI) HF subjects from the ADMIRE-HF trial. Cardiac and all-cause mortality data for 2-year follow-up were collected in the extension study (ADMIRE-HFX) and were examined in relation to extent and severity of voxel-based defects, the number of myocardial segments with significant dysinnervation (derived score ≥2), and (123)I-mIBG/(99m)Tc tetrofosmin mismatch quantitation. Cox proportional hazards and survival analyses were used to identify higher and lower risk groups and to define thresholds for optimal discrimination between the two. Two-year all-cause and cardiac mortality were not significantly different between IHF and NIHF subjects. Mortality was higher in patients with dysinnervation involving >50% of the myocardium. Highest cardiac mortality risk for IHF subjects was seen with perfusion defects involving 20-40% of the myocardium. By comparison, NIHF subjects with smaller perfusion abnormalities (<20% of myocardium), but with a large discrepancy between (123)I-mIBG and (99m)Tc tetrofosmin defect sizes, were at highest risk of cardiac death. CONCLUSIONS: Prognostic significance of patterns of (123)I-mIBG and MPI uptake differ between IHF and NIHF subjects. SPECT imaging may provide new insights into underlying disease processes in HF, including the degree of dysinnervation in areas with preserved myocardial perfusion in non-ischaemic HF patients.

Utility of Patient-Reported Outcome Instruments in Heart Failure.

Patient-reported outcomes (PRO) are defined as reports coming directly from patients about how they feel or function in relation to a health condition and its therapy. Although there are numerous compelling reasons why PRO could be an important help in clinical care, they have not evolved into clinical tools integrated into care. The purpose of this review is to assess existing PRO instruments for heart failure with respect to their psychometric properties and potential for use in clinical care. We performed a systematic search of articles published between July 2008 and January 2015 within the MEDLINE, PROMIS, PROQOLID, and Cochrane Library databases. Included instruments had to be developed and tested for heart failure and have had their development processes and psychometric properties described. A total of 31 instruments were identified, 9 of which met all inclusion criteria. After evaluating each remaining instrument in terms of psychometric and clinical criteria and symptom coverage, only 2 instruments-Minnesota Living with Heart Failure and Kansas City Cardiomyopathy questionnaire-met all evaluation criteria. Although clinically useful PRO instruments exist, increasing education to providers on the value and interpretability of PRO instruments, as well as a more streamlined approach to their implementation in the clinical setting is necessary. A clinical trial comparing the routine use of disease-specific PRO with clinical care could further support their incorporation into practice.

15-Year prognostic utility of coronary artery calcium scoring for all-cause mortality in the elderly.

INTRODUCTION: Prior studies have demonstrated a decline in the predictive ability of conventional risk factors (RF) with advancing age, emphasizing the need for novel tools to improve risk stratification in the elderly. Coronary artery calcification (CAC) is a robust predictor of adverse cardiovascular events, but its long-term prognostic utility beyond RFs in elderly persons is unknown. METHODS: A consecutive series of 9715 individuals underwent CAC scoring and were followed for a mean of 14.6 ± 1.1 years. Multivariable Cox proportional hazards regression (HR) with 95% confidence intervals (95% CI) was employed to assess the independent relationship of CAC and RFs with all-cause death. The incremental value of CAC, stratified by age, was examined by using an area under the receiver operator characteristic curve (AUC) and category-free net reclassification improvement (NRI). RESULTS: Of the overall study sample, 728 (7.5%) adults (mean age 74.2 ± 4.2 years; 55.6% female) were 70 years or older, of which 157 (21.6%) died. The presence of any CAC was associated with a >4-fold (95% CI = 2.84-6.59) adjusted risk of death for those over the age of 70, which was higher compared with younger study counterparts, or other measured RFs. For individuals 70 years or older, the discriminatory ability of CAC improved upon that of RFs alone (C statistics 0.764 vs. 0.675, P < 0.001). CAC also enabled improved reclassification (category-free NRI = 84%, P < 0.001) when added to RFs. CONCLUSION: In a large-scale observational cohort registry, CAC improves prediction, discrimination, and reclassification of elderly individuals at risk for future death.

Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality: A 15-Year Follow-Up Study of 9715 Patients.

BACKGROUND: Data regarding coronary artery calcification (CAC) prognosis in diabetic individuals are limited to 5-years follow-up. We investigated the long-term risk stratification of CAC among diabetic compared with nondiabetic individuals. METHODS AND RESULTS: Nine thousand seven hundred and fifteen asymptomatic individuals undergoing CAC scoring were followed for a median (interquartile range) of 14.7 (13.9-15.6) years. The incidence density rate and hazard ratios with 95% confidence intervals were used to calculate all-cause mortality. Incremental prognostic utility of CAC was evaluated using the area under the receiver operator characteristic curve and net reclassification improvement. Diabetics (54.7±10.8 years; 59.4% male) comprised 8.3% of the cohort (n=810), of which 188 (23.2%) died. For CAC=0, the rate of mortality was similar between diabetic and nondiabetic individuals for the first 5 years (P>0.05), with a nonlinear increased risk of mortality for diabetics after 5 years (P<0.05). The adjusted risk of death for those in the highest (CAC>400) versus the lowest (CAC=0) category of CAC increased by a hazards of 4.64 (95% confidence interval =3.74-5.76) and 3.41 (95% confidence interval =2.22-5.22) for nondiabetic and diabetic individuals, respectively. The presence of CAC improved discrimination (area under the receiver operator characteristic curve range: 0.73-0.74; P<0.01) and reclassification (category-free net reclassification improvement range: 0.53-0.50; P<0.001) beyond conventional risk factors in nondiabetic and diabetic individuals, respectively. CONCLUSIONS: CAC=0 is associated with a favorable 5-year prognosis for asymptomatic diabetic and nondiabetic individuals. After 5 years, the risk of mortality increases significantly for diabetic individuals even in the presence of a baseline CAC=0.

Long-Term Prognosis After Coronary Artery Calcium Scoring Among Low-Intermediate Risk Women and Men.

BACKGROUND: Cardiovascular screening of women using traditional risk factors has been challenging, with results often classifying a majority of women as lower risk than men. The aim of this report was to determine the long-term prognosis of asymptomatic women and men classified at low-intermediate risk undergoing screening with coronary artery calcium (CAC) scoring. METHODS AND RESULTS: A total of 2363 asymptomatic women and men with traditional risk factors aggregating into a low-intermediate Framingham risk score (6%-9.9%; 10-year predicted risk) underwent CAC scanning. Individuals were followed up for a median of 14.6 years. We estimated all-cause mortality using Cox proportional hazards models; hazard ratios with 95% confidence intervals were calculated. The area under the curve from a receiver operating characteristics curve analysis was calculated. There were 1072 women who were older (55.6 years) when compared with the 1291 men (46.7 years; P<0.0001), resulting in a greater prevalence and extent of CAC; 18.8% of women and 15.1% of men had a CAC score ≥100 (P=0.029). This older group of women had a 1.44-fold higher 15-year adjusted mortality hazard when compared with men (P=0.022). For women, the 15-year mortality ranged from 5.0% for those with a CAC score of 0 to 23.5% for those with a CAC score ≥400 (P<0.001). For men, the 15-year mortality ranged from 3.5% for those with a CAC score of 0 to 18.0% for those with a CAC score ≥400 (P<0.001). Women with CAC scores >10 had a higher mortality risk when compared with men. CONCLUSIONS: Our findings extend previous work that CAC effectively identifies high-risk women with a low-intermediate risk factor burden. These data require validation in external cohorts but lend credence to the use of CAC in women to improve risk detection algorithms that are currently based on traditional risk factors.

Coronary calcium scoring for long-term mortality prediction in patients with and without a family history of coronary disease.

OBJECTIVE: Minimal data are available regarding the long-term mortality risk of subclinical atherosclerosis using coronary artery calcium (CAC) scoring among patients with a family history (FH) of coronary artery disease (CAD). The aim of the present analysis was to assess the prognostic utility of CAC scoring among cohorts of young and older patients with and without a FH of CAD. METHODS: A total of 9715 consecutive asymptomatic patients, free of known CAD, underwent CAC scoring for cardiovascular risk assessment. The primary end point was all-cause mortality, with a median follow-up of 14.6 years. Unadjusted and risk-factor adjusted Cox proportional hazard modelling was employed. We calculated the area under the curve (AUC) from receiver operating characteristics analysis. RESULTS: 15-year all-cause mortality rates ranged from 4.7% to 25.0% for FH patients and from 5.0% to 38.0% for non-FH patients with CAC scores of 0 to >400 (p<0.0001). Effect modification by age altered the mortality risk of CAC among FH patients. For patients aged >60 years with FH of CAD, there was a significant improvement in the AUC with CAC over CAD risk factors (AUC: 0.539 vs 0.725, p<0.001). No such improvement was observed in FH patients aged <60 years (AUC: 0.636 vs 0.626, p=0.67). CONCLUSION: CAC effectively stratified mortality risk of patients with and without FH of CAD. However, for younger and lower-risk FH cohorts, CAC screening did not provide additive prognostic information beyond that of the traditional cardiac risk factors.

Contemporary cardiovascular device clinical trials (trends and patterns 2001 to 2012).

Device uptake and development have progressed over the last decade, but few quantitative data exist examining the overall operating characteristics and temporal trends of these clinical trials. We performed a systematic analysis of all cardiovascular device clinical trials from 2001 to 2012 published in medical and cardiovascular journals with the 8 highest impact factors. Of the 1,224 identified cardiovascular clinical trials, 299 (24.4%) focused specifically on devices. Each trial included a median of 335 patients (162 to 745) recruited from a median of 14 sites (3 to 38) over a median enrollment duration of 1.9 years (1.2 to 3.3). Median enrollment rate was 1.1 patients/site/month (0.5 to 4.2). Most device trials targeted coronary artery disease (55.2%), followed by arrhythmias (17.4%). Most were industry sponsored (53.6%) and included mortality as a primary end point (69.6%). The median number of patients (225 to 499, p <0.001 for trend) and enrolling sites (11 to 19, p = 0.07 for trend) increased from 2001 to 2012. During the study period, multinational enrollment grew and approached 50% (p = 0.03), whereas trials enrolling in North America exclusively decreased from 30% to 17% (p = 0.10 for trend). Approximately 70% of device trials met their primary end points; this rate did not significantly change over time. In conclusion, this descriptive study of the contemporary cardiovascular device clinical trials highlights recent trends toward larger, more international trial programs. These aggregate data may help inform future cardiovascular device development.

Mechanisms Contributing to the Progression of Ischemic and Nonischemic Dilated Cardiomyopathy: Possible Modulating Effects of Paracrine Activities of Stem Cells.

Over the past 1.5 decades, numerous stem cell trials have been performed in patients with cardiovascular disease. Although encouraging outcome signals have been reported, these have been small, leading to uncertainty as to whether they will translate into significantly improved outcomes. A reassessment of the rationale for the use of stem cells in cardiovascular disease is therefore timely. Such a rationale should include analyses of why previous trials have not produced significant benefit and address whether mechanisms contributing to disease progression might benefit from known activities of stem cells. The present paper provides such a reassessment, focusing on patients with left ventricular systolic dysfunction, either nonischemic or ischemic. We conclude that many mechanisms contributing to progressive left ventricular dysfunction are matched by stem cell activities that could attenuate the myocardial effect of such mechanisms. This suggests that stem cell strategies may improve patient outcomes and justifies further testing.

A 15-Year Warranty Period for Asymptomatic Individuals Without Coronary Artery Calcium: A Prospective Follow-Up of 9,715 Individuals.

OBJECTIVES: The aim of this study was to examine the long-term prognosis in asymptomatic individuals with a coronary artery calcium (CAC) score of 0 and its associated warranty period. BACKGROUND: Emerging evidence supports a CAC score of 0 as a favorable cardiovascular short-to intermediate-term prognostic factor. METHODS: A total of 9,715 individuals undergoing CAC imaging were stratified by age, Framingham risk score (FRS), and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) categories and followed for a mean of 14.6 years (range 12.9 to 16.8 years). Cox regression, area under the receiver-operating characteristic curve, and net reclassification information were used to assess all-cause mortality, discrimination, and reclassification of a CAC score of 0 compared with the FRS and NCEP ATP III, respectively. A warranty period was pre-defined as <1% annual mortality rate. Vascular age was estimated by linear regression. RESULTS: In 4,864 individuals with a baseline CAC score of 0 (mean age, 52.1 ± 10.8 years; 57.9% male), 229 deaths occurred. The warranty period of a CAC score of 0 was almost 15 years for individuals at low and intermediate risk with no significant differences regarding age and sex. A CAC score of 0 was associated with a vascular age of 1, 10, 20, and 30 years less than the chronological age of individuals between 50 and 59, 60 and 69, 70 and 79, and 80 years of age and older, respectively. The CAC score was the strongest predictor of death (hazard ratio: 2.67, 95% confidence interval: 2.29 to 3.11) that enabled discrimination and consistent reclassification beyond the FRS (area under the receiver-operating characteristic curve: 0.71 vs. 0.64, p < 0.001) and NCEP ATP III (area under the receiver-operating characteristic curve: 0.72 vs. 0.64, p < 0.001). CONCLUSIONS: A CAC score of 0 confers a 15-year warranty period against mortality in individuals at low to intermediate risk that is unaffected by age or sex. Furthermore, in individuals considered at high risk by clinical risk scores, a CAC score of 0 confers better survival than in individuals at low to intermediate risk but with any CAC score.