Non-cardiovascular Comorbidities Research Articles

Vitamin D as a predictor of clinical response among patients with cardiac resynchronization therapy (CRT)

AbstractIntroductionCardiovascular and noncardiovascular comorbidities have been recognized as predictors of clinical response in patients receiving cardiac resynchronization therapy (CRT). However, data on vitamin D as a predictor of CRT response are conflicting.MethodWe identified studies from MEDLINE and Embase databases, searching from inception to May 2024, to investigate the association between 25‐OH vitamin D levels before CRT implantation and outcomes. Studies had to report 25‐OH vitamin D levels or the proportion of patients with vitamin D insufficiency and categorize outcomes as CRT responders or nonresponders. We extracted mean 25‐OH vitamin D and standard deviations for both groups from each study and calculated the pooled mean difference (MD). We also retrieved risk ratios, and 95% confidence intervals (CIs) for the association between vitamin D insufficiency and lack of CRT response, combining them using the generic inverse variance method.ResultsOur meta‐analysis included four studies. CRT responders had higher levels of 25‐OH vitamin D than nonresponders, with a pooled MD of 8.04 ng/mL (95% CI: 3.16–12.93; I2 = 48%, p < .001). Patients with vitamin D insufficiency before implantation had higher odds of lacking response to CRT, with a pooled RR of 3.28 (95% CI: 1.43–7.50; I2 = 0%, p = .005) compared to those with normal vitamin D.ConclusionsCRT responders had higher 25‐OH vitamin D levels compared to nonresponders. Vitamin D insufficiency was associated with a higher risk of nonresponse to CRT. These findings highlight the importance of monitoring and managing vitamin D levels in these patients.

Profile and Prognostic Impact of Multimorbidity in Elderly Patients with Heart Failure: Are there Differences between Men and Women?

Heart failure (HF) represents a pathology in constant growth, but, despite the fact that a significant proportion of its population is comprised of elderly patients, they are not adequately represented in clinical trials or registries. They constitute a heterogeneous population with their particularities and interaction of the multiple comorbidities that characterize this age group, which makes the clinical course, prognosis and outcomes of the disease different. Compared to men, women with HF tend to be older, with a greater burden of non-cardiovascular comorbidities, less ischemic heart disease and preserved ventricular function in most cases. This fact translates into worse self-perceived quality of life, with lower hospitalization and mortality rates. Moreover, paradoxically, women are less likely to receive treatment recommended by clinical practice guidelines, including revascularization and device placement. As there are not enough representative studies of this population, the reasons for these results with better prognosis and relatively benign impact in the elderly female population are unknown, which is why it is necessary to continue with research in order to obtain greater evidence of the exposed gaps.

Predicting Out-of-Hospital Cardiac Arrest in the General Population Using Electronic Health Records.

The majority of out-of-hospital cardiac arrests (OHCAs) occur among individuals in the general population, for whom there is no established strategy to identify risk. In this study, we assess the use of electronic health record (EHR) data to identify OHCA in the general population and define salient factors contributing to OHCA risk. The analytical cohort included 2366 individuals with OHCA and 23 660 age- and sex-matched controls receiving health care at the University of Washington. Comorbidities, electrocardiographic measures, vital signs, and medication prescription were abstracted from the EHR. The primary outcome was OHCA. Secondary outcomes included shockable and nonshockable OHCA. Model performance including area under the receiver operating characteristic curve and positive predictive value were assessed and adjusted for observed rate of OHCA across the health system. There were significant differences in demographic characteristics, vital signs, electrocardiographic measures, comorbidities, and medication distribution between individuals with OHCA and controls. In external validation, discrimination in machine learning models (area under the receiver operating characteristic curve 0.80-0.85) was superior to a baseline model with conventional cardiovascular risk factors (area under the receiver operating characteristic curve 0.66). At a specificity threshold of 99%, correcting for baseline OHCA incidence across the health system, positive predictive value was 2.5% to 3.1% in machine learning models compared with 0.8% for the baseline model. Longer corrected QT interval, substance abuse disorder, fluid and electrolyte disorder, alcohol abuse, and higher heart rate were identified as salient predictors of OHCA risk across all machine learning models. Established cardiovascular risk factors retained predictive importance for shockable OHCA, but demographic characteristics (minority race, single marital status) and noncardiovascular comorbidities (substance abuse disorder) also contributed to risk prediction. For nonshockable OHCA, a range of salient predictors, including comorbidities, habits, vital signs, demographic characteristics, and electrocardiographic measures, were identified. In a population-based case-control study, machine learning models incorporating readily available EHR data showed reasonable discrimination and risk enrichment for OHCA in the general population. Salient factors associated with OCHA risk were myriad across the cardiovascular and noncardiovascular spectrum. Public health and tailored strategies for OHCA prediction and prevention will require incorporation of this complexity.

Operative Repair of Aortopulmonary Window: A 25-Year Experience.

Background: Aortopulmonary window (APW) is a rare anomaly with variable morphology and associated cardiac anomalies. We evaluated impact of patient and operative factors on mid-term outcomes following APW repair. Methods: Twenty-nine patients underwent surgical APW repair at our institution from 1996 to 2022. Eight (28%) had simple APW, accompanied by only atrial septal defect or patent ductus arteriosus; 21 (72%) had complex APW with additional cardiovascular lesions, including nine with interrupted aortic arch. Median operative age was 19 days (range 2 days-1.5 years) via single-patch (n = 12, 41%), double-patch (n = 15, 52%), or ligation and division (n = 2, 7%). Results: The only mortality occurred in-hospital 1.4 years postoperatively following remote myocardial infarction. Factors associated with longer postoperative length of stay were complex APW (P = .003), genetic syndrome (P = .003), noncardiovascular comorbidities (P = .002), lower birth weight (P = .03), and lower operative weight (P = .03). Six patients (21%) with complex APW underwent unplanned cardiothoracic reintervention(s), including two with arch reintervention following arch advancement for interruption. Reintervention-free survival was similar for simple versus complex APW, operative age categories, and repair techniques. At median follow-up 5.5 years postoperatively, no patients had residual APW or persistent pulmonary hypertension, 1 (3%) had greater than mild ventricular dysfunction, and 25 (89% survivors) had NYHA class I functional status. Conclusions: Operative APW repair has excellent mid-term survival, durability, and functional status, regardless of operative age, cardiovascular comorbidities, or repair technique. Cardiac and noncardiac comorbidities may be associated with prolonged length of stay.

The impact of multimorbidity and functional limitation on quality of life in patients with heart failure: A multi-site study.

Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health-related quality of life in patients with HF is not well understood. Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF-related prescription drugs from four U.S. institutions were mailed a survey to measure patient-centric factors including functional status (activities of daily living [ADLs]) and health-related quality of life (PROMIS-29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non-cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS-29 sub-scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66-4.45), depression (OR: 3.11, 95% CI: 2.39-4.06), and fatigue (OR: 4.19, 95% CI: 3.25-5.40); worse sleep (OR: 2.14, 95% CI: 1.69-2.72) and pain (OR: 6.73, 95% CI: 5.15-8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19-12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. Patients with only functional limitation have similar poor health-related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well-being of patients with HF.

Abstract 48: Racial and Ethnic Disparities in Cardiovascular Multimorbidity Progression Among Older United States Adults

Introduction: There is a knowledge gap in the potential unequal burden and progression of cardiovascular multimorbidity. Understanding the progression of cardiovascular multimorbidity and recognizing racial and ethnic disparities are needed to develop effective strategies to achieve health equity. Our objective is to investigate racial and ethnic disparities in the development and progression of cardiovascular multimorbidity among older adults in the United States and estimate relative life expectancies among patients with severe multimorbidity. Hypothesis: We hypothesized that life expectancy among older adults with severe cardiovascular multimorbidity is inversely related to the number of comorbid conditions and varies by race and ethnicity. Methods: Repeated cross-sectional cohort study of inpatient, outpatient, and carrier claims for a 5% nationwide Medicare sample. We included Medicare beneficiaries aged 65 or older enrolled in Medicare Fee-For-Service program from 2010 to 2020 and living in the continental United States. Multistate life table models were employed to estimate cardiovascular disease (CVD) progression and total life expectancies from ages 65 to 85 years. Progression probabilities and life expectancies were adjusted for age, non-cardiovascular comorbidities, and Medicaid dual eligibility. A microsimulation approach was utilized to derive life tables, and bootstrapping was used to estimate variability. The primary outcome was the development and progression of cardiovascular multimorbidity, defined by the number of major cardiovascular conditions (atrial fibrillation, acute myocardial infarction, heart failure, stroke, and chronic ischemic heart disease). Comorbidities were assessed using validated algorithms based on diagnostic codes billed over a 1-year lookback period, and beneficiaries were followed forward from their index date. Results: Of 2,189,633 beneficiaries, the median age was 69, median follow-up duration was 6 years. The cohort mainly consisted of individuals who are Non-Hispanic White (84.4%, n=1,848,410), followed by individuals who are Non-Hispanic Black (8.2%, n=179,694) and individuals from other racial or ethnic groups (7.4%, n=161,529. Non-Hispanic Black beneficiaries had higher odds of multimorbidity progression compared to Non-Hispanic White beneficiaries. Specifically, those initially with one CVD had elevated odds of developing multiple severe CVDs (OR range: 1.02-1.09). Furthermore, they generally had higher odds of progressing to a greater burden of CVD multimorbidity (OR range: 1.00-1.25). Conclusions: These findings suggest persistent racial and ethnic disparities in cardiovascular multimorbidity progression, identifying a potentially important target for the promotion of health equity.

Abstract P304: Sex Differences for the Progression of Cardiovascular Multimorbidity in Older Adults in the United States

Introduction: Understanding the progression of cardiovascular multimorbidity and recognizing differences are needed to develop effective strategies to improve health outcomes. There is a knowledge gap in the potential unequal burden and progression of cardiovascular multimorbidity. Our objective is to investigate sex differences in the progression of cardiovascular multimorbidity among older adults in the US and estimate relative life expectancies among patients with severe multimorbidity. Hypothesis: We hypothesized that life expectancy among older adults with severe cardiovascular multimorbidity is inversely related to the number of comorbid conditions and progresses more acutely in males. Methods: Repeated cross-sectional cohort study of inpatient, outpatient, and carrier claims for a 5% nationwide Medicare sample. We included Medicare beneficiaries aged 65 or older enrolled in Medicare Fee-For-Service program from 2010 to 2020 and living in the continental US. Multistate life table models were employed to estimate cardiovascular disease (CVD) progression and total life expectancies from ages 65 to 85 years. Progression probabilities and life expectancies were adjusted for age, non-cardiovascular comorbidities, and Medicaid dual eligibility. A microsimulation approach was utilized to derive life tables, and bootstrapping was used to estimate variability. The primary outcome was the development and progression of cardiovascular multimorbidity, defined by the number of major cardiovascular conditions (atrial fibrillation, acute myocardial infarction, heart failure, stroke, and chronic ischemic heart disease). Comorbidities were assessed using validated algorithms based on diagnostic codes billed over a 1-year lookback period, and beneficiaries were followed forward from their index date. Results: Of 2,189,633 beneficiaries, the median age was 69, median follow-up was 5 years, and 55.9% were female. For male beneficiaries, odds of developing cardiovascular comorbidities were significantly higher than for females, with odds ratios ranging from 1.20 (95% CI 1.19-1.21) for one CVD to 1.97 (95% CI 1.88-2.06) for 1 or more of the 4 CVD comorbidities. Men with 1 CVD at baseline had significant odds of developing 2 (OR: 1.10, 95% CI 1.09-1.11) and four CVDs (OR: 1.29, 95% CI 1.24-1.34), as well as a significant mortality risk (OR: 1.19, 95% CI 1.18-1.21). However, for men with 4 CVDs, the odds of progressing to 5 were not significant (OR: 1.00, 95% CI 0.97-1.04). Across levels of baseline multimorbidity, male beneficiaries had significantly elevated mortality risks compared to females, with the highest risk for those with no baseline CVD (OR: 1.50, 95% CI 1.48-1.52). Conclusions: These findings suggest persistent sex differences in cardiovascular multimorbidity progression, identifying a potentially important target for the improvement of health outcomes.

Considerations Regarding Management of Heart Failure in Older Adults.

Understanding noncardiovascular comorbidities and geriatric syndromes in elderly patients with heart failure (HF) is important as the average age of the population increases. Healthcare professionals need to consider these complex dynamics when managing older adults with HF, especially those older than 80. A number of small studies have described associations between HF and major geriatric domains. With information on patients' cognitive, functional decline, and ability to adhere to therapy, physicians can plan for individualized treatment goals and recommendations for these patients.

Prevalence and patterns of comorbidities in older people with type 2 diabetes in Australian primary care settings.

The aim of this study was to identify the prevalence and patterns of comorbidity in community-dwelling older people with type 2 diabetes mellitus (T2DM) attending general practice settings in Australia. This study involveda cross-sectional analysis using the Bettering the Evaluation and Care of Health (BEACH) sub-study data. In a series of sub-studies, a representative sample of general practitioners was asked to record all diagnosed chronic conditions for patients at 40 consecutive encounters using structured paper-based recording forms. The dataset was analysed with descriptive analyses, and exploratory factor analyses were applied to examine comorbidity patterns. Of the 14,042 patients aged 65 years or older, 2688 had a diagnosis of T2DM (19%). Of the 2688 patients with T2DM, hypertension was present in 67% (95% CI: 64.6-70.0), followed by arthritis 52% (95% CI: 48.8-54.8), hyperlipidaemia 45% (95% CI: 41.8-47.9), ischemic heart disease, 23% (95% CI: 20.7-24.9), depression 16% (95% CI: 48.8-54.8), atrial fibrillation 10% (95% CI: 8.9-11.6), congestive heart failure 7% (95% CI: 6.0-8.1), stroke/cerebrovascular accident 7% (95% CI: 5.4-8.2) and peripheral vascular disease 5% (95% CI: 4.4-6.2). We identified two comorbidity patterns among older people with T2DM. The first were psychological and musculoskeletal conditions and the second were cardiovascular conditions and chronic renal failure. The prevalence of cardiovascular and non-cardiovascular comorbidities in community-dwelling older people with T2DM was high. Adequate primary care strategies should be in place to support the long-term care for this population.

A contemporary update on cancer and takotsubo syndrome.

Takotsubo syndrome (TTS) is characterized by a transient left ventricular systolic dysfunction, burdened by significant acute and long-term mortality and morbidity. The prognosis of TTS, especially in the long-term, is influenced by both non-cardiovascular (non-CV) and CV comorbidities, among which cancer is one of the most common. The presence of a malignancy is proven to be associated with higher mortality in TTS. Moreover, a number of anticancer treatments has been reported to possibly cause TTS as a form of cardiotoxicity, even though clearcut associations are lacking. The aim of this narrative review is to sum up contemporary knowledge on the association of cancer and TTS, addressing unmet needs and practical implications. The importance of a close collaboration between cardiologists and oncologists is herein highlighted, both to allow an adequate management of the acute TTS phase, and to actively and safely return to the oncologic management once the acute setting is resolved.

Disparities in heart failure between White, Black, and Hispanic young adults: insights from the National Health and Nutrition Examination Survey.

The prevalence of heart failure (HF) is increasing among young adults in the United States with pervasive racial and ethnic differences in this population. To evaluate contemporary associations between race and ethnicity, clinical comorbidities, and outcomes among young to middle-aged adults with HF. A retrospective analysis was performed using the National Health and Nutrition Examination Survey. All participants with a self-report of HF aged 20-64 years from 2005 to 2018 were included and stratified by race and ethnicity [non-Hispanic (NH) Whites, NH Blacks, and Hispanics]. Data on baseline characteristics including age, sex, marital status, citizenship, education level, body mass index, insurance, waist circumference, cigarette smoking, marijuana use, and relevant clinical comorbidities were included. Weighted logistic regression was performed to estimate adjusted odds ratios (aOR) to determine the association of race and ethnicity with HF. Cox proportional-hazards models were used to assess the association of race and ethnicity with all-cause and cardiac mortality. A total of 1,940,447 young to middle-aged adults had self-reported HF between 2005 and 2018, of whom 61% were NH White, 40% were NH Black, and 22% were Hispanic. When compared with NH White adults, NH Black adults had higher odds of HF adjusted for age, sex, insurance status, marital status, education level, citizenship status, and clinical comorbidities (adjusted aOR 2.63, 95% CI: 1.71-4.05, p < 0.001). There was no significant difference in the odds of HF between Hispanic and NH White adults (aOR 1.18, 95% CI: 0.64-2.18, p = 0.585). NH Black adults had higher mean systolic and diastolic blood pressure, and a comparable or lower burden of cardiovascular and non-cardiovascular clinical comorbidities compared with NH White and Hispanic adults. No statistical significance was noted by race and ethnicity for all-cause and cardiac mortality during a follow-up of 5 years. NH Black young to middle-aged adults were more likely to have HF which may be related to higher blood pressure given the largely similar burden of clinically relevant comorbidities compared with other racial and ethnic groups.

Temporal trends in the prevalence of cardiovascular and non-cardiovascular comorbidities in patients presenting with acute myocardial infarction: Insights from the AMIS Plus registry

Abstract Background Little is known about temporal trends in the prevalence of cardiovascular and non-cardiovascular comorbidities in patients presenting with acute myocardial infarction (AMI). Methods AMIS Plus registry patients enrolled between 2004 and 2021 were stratified based on comorbidities in 3 groups: (1) «cardiovascular comorbidity»: at least one among past history of myocardial infarction, coronary artery bypass grafting or percutaneous coronary intervention, heart failure, peripheral vascular disease, cerebrovascular disease, or atrial fibrillation; (2) «non-cardiovascular comorbidity»: at least one among dementia, chronic lung disease, connective tissue disease, peptic ulcer disease, moderate or severe renal disease, diabetes, liver disease, or cancer disease; and (3) «any comorbidity»: at least one of the mentioned comorbidities. Prevalence and mortality were analysed according to the type of comorbidity in 2-year periods and stratified by sex. Temporal trends were analysed using the Mantel-Haenszel linear-by-linear association Chi-squared test. Results Among the 48’848 patients enrolled, 24’215 (49.6%) had at least one comorbidity. Of these, 17’441 (72.0%) were male and 6’774 (28.0%) female. Over the years, there was a significant decrease in the prevalence of «any comorbidity» (p&amp;lt;0.001) as well as «cardiovascular comorbidity» (p&amp;lt;0.001). A significant decrease in the prevalence of «any comorbidity» as well as «cardiovascular comorbidity» was detected for both sexes. With respect to the prevalence of «non-cardiovascular comorbidity», a significant reduction over time was observed in men but not in women. The reduction of in-hospital mortality over time was significant across all groups, overall and for both sexes individually. Conclusions Over more than a decade, a significant reduction in the prevalence of comorbidities was observed in patients presenting with AMI, with the exception of non-cardiovascular comorbidities in women. This reduction may have contributed, in addition to the improvements in pharmacologic treatments as well as in revascularization, to the improved survival observed over time.Temporal trends of comorbidities

Sex differences in characteristics, microbiology, management, and outcomes in infective endocarditis

Abstract Background Infective endocarditis affects male patients more frequently, yet female sex has been associated with higher mortality rate in prior smaller studies. Unselected nationwide studies on sex differences in infective endocarditis are sparse and may help identify sex-related and universal prophylactic strategies. Purpose To investigate sex related differences in patient characteristics, practice patterns and outcomes in patients with infective endocarditis. Methods Between 2010–2020, we identified and characterized all patients with infective endocarditis according to sex. We used data from the Danish national registries including microbiological data, and outcome. Frailty was assessed by the sum of cardiovascular and non-cardiovascular comorbidities in each patient using the Hospital Frailty Risk Score. Mortality was compared in unadjusted analyses using Kaplan-Meier estimates for 90-day mortality following hospital admission and 5-year mortality following hospital discharge. In adjusted analyses, Cox regression was used for comparison of 90-day and 5-year mortality. Results We identified 6,259 patients with infective endocarditis including 2,047 (32.7%) female patients and 4,212 (67.3%) male patients. Female patients were older (median age 75.0 years (IQR 64.3–82.2 vs. 71.7 years (IQR 61.7–78.9) and more frail (Intermediate frailty: 36.5% vs. 33.1%, High frailty: 11.4% vs. 9.2%, p&amp;lt;0.001). Female patients had lower education level, lower income and were more likely to live alone. Female patients had less cardiovascular comorbidity than male patients such as ischemic heart disease (25.2% vs. 34.8%), congestive heart failure (20.3% vs. 24.0%), prior myocardial infarction (7.8% vs. 14.3%), prosthetic heart valve (16.5% vs. 20.3%), and CIED (12.2% vs. 18.7%) (p&amp;lt;0.01). Staphylococcus aureus was the most common microorganism in both sexes (34.6% vs. 28.8%), but fewer female patients had Enterococcus species than male patients (10.5% vs. 18.1%). Female patients were less often surgically treated (14.0% vs. 21.2%). The cumulative 90-day incidences of mortality from hospital admission were 30.9% (95% CI 28.9%–32.9%) in females and 23.6% (95% CI 22.3%–24.9%) in males (Figure 1). The cumulative 5-year incidences of mortality from hospital discharge were 59.8% (95% CI 57.4%–62.0%) in female patients and 53.0% (95% CI 51.3%–54.6%) in male patients. In adjusted analysis, female sex was associated with increased 90-day mortality (adj. HR 1.22, 95% CI 1.10–1.36), but no difference was found in 5-year mortality (adj. HR 1.02, 95% CI 0.93–1.12). Conclusion In infective endocarditis, female sex is associated with an increased 90-day mortality despite adjusting for age and frailty. However, this association is not found in long-term mortality. Female patients differ from male patients with lower prevalence of Enterococcus infective endocarditis and lower rates of surgery. Further research is needed to understand why these differences persist.

Sex specific lifetime risk of incident cardiovascular events. Results from a large British population-based cohort study

Abstract Background There are marked sex differences in cardiovascular (CV) disease, most characteristically with men having a higher risk of coronary heart disease and myocardial infarction (MI). The sex differences in the absolute lifetime risk of CV disease as well as the different profiles of first incident CV events remain poorly described. Purpose Using data from a large British population-based cohort study with long follow-up, we aimed to compare the sex differences in the lifetime risk of incident CV events (MI, stroke, atrial fibrillation (AF), heart failure (HF), peripheral artery disease (PAD) and CV mortality). Methods Eligible participants at the study baseline (1993-1998) were included and followed up until March 2018. Cause-specific hazard ratios were ascertained using Weibull regressions. The sex-specific lifetime risks of each outcome were ascertained using Weibull regressions accounting for the competing risk of death. All models were adjusted for time-updated covariates: ethnicity, Townsend index of deprivation, systolic blood pressure, hypercholesterolaemia, diabetes, smoking, alcohol intake, physical activity, body mass index, fruit/vegetable intake, non-cardiovascular conditions and medication. Results 8975 men and 11,330 women aged ≥40 and free of CV disease at baseline were included. The median follow-up was 22.3 years. Compared to women, men were more likely to be older, have higher systolic blood pressure, higher BMI and be less physically active. Men were less likely to have prevalent non-cardiovascular comorbidities. The adjusted cumulative incidence of a CV event ranged between 13.8%-28.2% for men and 7.5%-21.2% for women (Figure 1). The lifetime risk of CV mortality was 28.7% for men and 22.9% for women. Compared to women, the relative risk of incident CV events for men was two-fold higher for MI (cause specific hazard ratio (95% confidence interval) – 2.05 (1.83-2.30)) and PAD (2.02 (1.83-2.23)), 50% higher for HF (1.52 (1.39-1.66)) and AF (1.51 (1.40-1.62)), 42% for cardiovascular mortality (1.42 (1.32-1.53)) and 12% for stroke (1.12 (1.03-1.22)). There were also sex differences in the lifetime incidence of different types of first CV event (Figure 2). Amongst men, MI had the highest incidence as a first CV event throughout lifetime. The earliest incidence rise in MI occurred by 50 years and was followed by AF, PAD, stroke and heart failure over the following decades. In women, the incidence of MI as a first CV event was highest between 50-60 years but was overtaken by AF by 65 years and stroke by 70 years. Conclusions Men had a higher risk of incident cardiovascular disease throughout their lifetime than women, but these sex differences were most pronounced for MI and PAD, followed by AF, HF and CV mortality. These were also reflected in the different sex profiles characterising the type of first incident CV event. These differences highlight the importance of tailoring sex-specific primary preventative strategies.Figure 1Figure 2

End of life after transcatheter aortic valve implantation

Abstract Background Survival after transcatheter aortic valve implantation (TAVI) has drastically improved over time. Thus, patients may be more susceptible to experience multimorbidity and non-cardiovascular hospitalizations in their final years of life; however, the extent of which comorbidities impact end of life after TAVI is unknown. Purpose To describe end of life after TAVI in terms of the burden and causes of hospitalization compared with non-TAVI controls from the general population. Methods All Danish patients who underwent TAVI during 2008–2021 were identified at date of death. Patients who died within one year from TAVI were excluded. Matching was performed on sex, age at death, and calendar year of death in a 1:10 ratio. Patient characteristics at time of death were reported. Cumulative time in hospital was calculated and compared for the TAVI group and matched controls. Further, the cause for all inpatient hospitalizations were categorized as heart failure, cardiovascular (excluding heart failure), non-cardiovascular, and symptoms (e.g., dyspnea, vomiting) according to the primary discharge code. Results After exclusion, 2,041 deaths among patients with TAVI (median time from TAVI to death: 1,352 days [25th-75th percentile: 841–1,980]) were matched to 20,410 deaths among controls (standardized mean differences &amp;lt; 0.1 for all matching variables). Due to matching, age was 86 years, and 54.7% were males in both groups. However, frailty was higher in the TAVI group (frail TAVI group: 86.5% vs. controls: 76%). Cardiovascular and non-cardiovascular comorbidity burden was higher in the TAVI group (e.g., heart failure: 57.6% vs. 18.4%; chronic obstructive pulmonary disease: 27.9% vs. 18.8%; chronic kidney disease: 25.7% vs. 12.9%). However, history of cancer was lower in the TAVI group (21.7% vs. 26.3%). Time in hospital in the last year of life was higher in the TAVI group: 27.2% were hospitalized &amp;gt;28 days and 11.5% were never hospitalized compared with 17.1% and 22.7% for controls, respectively (Figure 1). In both groups, non-cardiovascular hospitalizations were most common towards end of life. Indeed, 70.5% of hospitalizations during the last year of life for TAVI patients were due to non-cardiovascular causes. Moreover, in both groups, non-cardiovascular hospitalizations became more frequent closer to time of death (Figure 2). However, heart failure hospitalizations were more common in the TAVI group compared with controls. Conclusion End of life for TAVI patients was characterized by substantial multimorbidity and hospitalizations are frequent. Although heart failure hospitalizations were more common for TAVI patients than their matched controls, non-cardiovascular hospitalizations were more frequent in both groups. This highlights the need for a multidisciplinary approach to improve quality of life towards end of life after TAVI.Figure 1

The effect of a mobile health technology integrated care across multimorbidity patterns in atrial fibrillation patients: a latent-class ancillary analysis from the mAFA-II randomised clinical trial

Abstract Background Multimorbidity confers an increasing health problem, especially with the progressive aging of the population. Hypertension, diabetes mellitus (DM), chronic heart failure (CHF) are highly prevalent and ultimately entails multimorbidity in patients with atrial fibrillation (AF), with detrimental effects on prognosis. The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) cluster randomised trial showed the efficacy of a mobile health implemented ‘Atrial fibrillation Better Care’ (ABC) pathway (mAFA intervention) for an integrated care management of patients with AF. Purpose Evaluate the effect of mAFA intervention according to the patterns of multimorbidity as identified through a latent-class analysis (LCA) approach. Methods The mAFA-II trial is a cluster randomised trial that enrolled adults AF patients between June 2018 and August 2019 in 40 centres in China. Clusters were randomised to mAFA intervention or usual care. We performed a LCA according to several variables (including age over 75, coronary artery disease (CAD), CHF, chronic kidney disease (CKD), DM, hypertension, peripheral artery disease and prior ischemic stroke), and modal posterior probability was used to define class membership of patients. The interaction between the effect of mAFA intervention and class allocation on the risk of the primary composite outcome of stroke, thromboembolism, all-cause death, and rehospitalizations was assessed through multivariable Cox-regression models, and results were expressed as adjusted Hazard Ratio (aHR) and 95% Confidence Intervals (95%CI). Results 3324 AF patients (mean age 68.5±13.9; 38.0% females) were enrolled in the trial and included in the analysis. We identified 3 comorbidity patterns, which differed according to prevalence of conditions and risk factors: (i) low morbidity pattern (n=1234, 37.1%), (ii) hypertensive/CAD pattern (n=1534, 46.2%), and (iii) mixed morbidity pattern (n=556, 16.7%). Overall, subjects in the mixed morbidity patterns were older, had a higher burden of diseases, and showed the highest prevalence of CKD, diabetes and history of stroke (Figure 1). Multivariable Cox-regression analysis showed a significant interaction between the effect of mAFA intervention and comorbidity patterns on the risk of the primary composite outcome (pint= 0.004), with the effect of mAFA intervention being greatest in the low morbidity pattern (aHR:0.08, 95%CI:0.02-0.32) and somewhat diluted in the mixed morbidity pattern group with a trend towards lower risk (aHR:0.69, 95%CI:0.37-1.28, Figure 2). Conclusions Multimorbidity is common and heterogeneous in AF patients. The effect of a mHealth-technology implemented ABC pathway appeared lower in magnitude in those patients with mixed morbidity patterns, suggesting that these patients require further interventions, aiming at addressing non-cardiovascular comorbidities and overall clinical complexity, to improve their outcomes.Clusters distributionCox-regression models for interaction

Abstract 12926: Characteristics of Tafamidis-Treated Patients With Mixed Phenotype Transthyretin Amyloidosis: A Real-World Study in the Medicare Fee-for-Service Population

Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is highly heterogeneous, characterized by predominantly cardiac, predominantly neurologic or mixed phenotypes. Diagnosis of mixed phenotype is often delayed, due in part to fragmented care. Research based on administrative claims data has improved knowledge of the disease, but investigation of the mixed phenotype has been limited by deficiencies in ICD diagnosis codes. Hypothesis: Proxy algorithms can be used to identify and characterize mixed phenotype ATTR amyloidosis in Medicare patients. Methods: This noninterventional, retrospective, observational cohort study was conducted using de-identified patient data from the US Medicare database (Jan 1, 2016-Dec 31, 2021). Based on literature review and clinician consultation, 3 distinct proxy algorithms were developed to select 3 cohorts of tafamidis-treated patients with possible mixed phenotype ATTR amyloidosis ( Figure ). Baseline patient characteristics were analyzed descriptively. Results: In 1,243 patients, mean (SD) age ranged from 76.0 (6.3)-79.5 (6.5) y, and 68-83% were men. Comorbidity burden was similar across cohorts (Charlson comorbidity indices: 1.6 [0.9]-1.7 [1.0]). The most common cardiovascular comorbidities were hypertensive diseases, arrhythmia, conduction disorders and LVH; the most common noncardiovascular comorbidities were cataracts, chronic and acute kidney disease, constipation and diabetes ( Table ). Conclusions: In this real-world study, proxy algorithms helped identify and characterize mixed phenotype ATTR amyloidosis in Medicare patients. Additional research is needed to further validate these algorithms.

Underutilization of Mineralocorticoid Antagonists in Patients With Heart Failure With Reduced Ejection Fraction

BackgroundIt is unknown how the efficacy and safety of mineralocorticoid receptor antagonists vary according to duration of heart failure with reduced ejection fraction (HFrEF). ObjectivesIn this study, we sought to evaluate the safety and efficacy of eplerenone according to duration of HFrEF. MethodsIn the EMPHASIS-HF trial, 3 patient groups were created according to HFrEF duration: <1 year, 1 to <5 years, and ≥5 years. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Outcomes were adjusted for prespecified prognostic variables and examined with the use of Cox regression models. ResultsThe numbers of patients in each group were: 975, <1 year; 769, 1 to <5 years; and 988, ≥5 years. Patients with longer-standing HF were older and more frequently had cardiovascular and noncardiovascular comorbidities. The rate of the primary outcome (per 100 person-years) increased with HFrEF duration: 9.8 (95% CI: 8.4-11.4) for <1 year, 13.5 (95% CI: 11.6-15.7) for 1 to <5 years, and 17.6 (95% CI: 15.6-19.8) for ≥5 years. The benefits of eplerenone were consistent across HF duration: HRs for the primary outcome were 0.57 (95% CI: 0.42-0.79) for <1 year, 0.81 (95% CI: 0.60-1.10) for 1 to <5 years, and 0.61 (95% CI: 0.48-0.78) for ≥5 years; Pinteraction = 0.24. The absolute benefit was greatest in the longest-duration group: the number needed to treat for the primary outcome was 14 for <1 year, 13 for 1 to <5 years, and 10 for ≥5 years duration. ConclusionsPatients with longer-standing HFrEF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent regardless of HFrEF duration. (A Comparison of Outcomes in Patients in NYHA Class II Heart Failure When Treated With Eplerenone or Placebo in Addition to Standard Heart Failure Medicines [EMPHASIS-HF]; NCT00232180)

Blood pressure control and treatment burden from comorbidities

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the National Research Foundation of Korea grants funded by the Korea government (MEST) Background Achieving the optimal target blood pressure is important for patients with hypertension to prevent cardiovascular complications. Adhering to recommended therapeutic regimens is crucial to control the blood pressure. However, patients with non-cardiovascular comorbid conditions along with hypertension may experience difficulty performing adequate self-care of hypertension and achieving the optimal target blood pressure because they need to simultaneously manage hypertension and comorbidities. Treatment burden refers to workloads to manage chronic conditions and their impact. Thus, it is possible that the burden of treatment associated with managing multiple conditions adversely affects blood pressure control. Purpose To examine whether treatment burden was associated with achieving the optimal target blood pressure in patients with hypertension and non-cardiovascular comorbidities. Methods Patients with hypertension and non-cardiovascular comorbidities were recruited and asked to complete the questionnaires via online survey. Treatment burden was measured with the Multimorbidity Treatment Burden Questionnaire. Comorbid conditions that were diagnosed and/or treated were measured with the list developed to document self-reported chronic conditions in primary care. Patients were asked to report their blood pressure readings that were measured most recently within three months. Based on their blood pressure readings, patients were classified into two groups: controlled group with the blood pressure readings of &amp;lt; 140/90 mmHg and uncontrolled group with the blood pressure readings of 140/90 mmHg or above. To determine whether treatment burden was associated with blood pressure group assignment, multivariable logistic regression was used after adjusting for covariates (i.e., age, gender, education levels, employment status, periods since hypertension diagnosis, the number of non-cardiovascular comorbidities, and self-care maintenance of hypertension). Results A total of 280 patients with hypertension and non-cardiovascular comorbidities (52 years old, 33.2% female) were included in this study. Patients had an average of 3 comorbidities (SD 1.3). Of 280 patients, 153 (54.6%) had the blood pressure readings of &amp;lt;140/90 mmHg (i.e., controlled group). The multivariate logistic regression model shows that patients with greater levels of treatment burden were less likely to be in the controlled group after adjusting for covariates (adjusted odds ratio: 0.98, 95% confidence interval: 0.971-0.997). Conclusion We found that treatment burden was negatively associated with achieving the optimal target blood pressure in patients with hypertension and non-cardiovascular comorbidities. It is important for clinicians to assess patients’ burden of treatment associated with managing hypertension and comorbidities when discussing blood pressure management.

Mediators of Improvement in TAVR Outcomes Over Time: Insights From the STS-ACC TVT Registry.

Over the past decade, there has been substantial improvement in outcomes after transcatheter aortic valve replacement. Many patient and procedural factors have also changed over that time, making it challenging to untangle the drivers of those improvements. Among patients who underwent transcatheter aortic valve replacement from 2012 to 2018 within the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry, we examined the relative contribution of changes in patient factors, device modifications, improving experience/skill, and advances in periprocedural care to the observed improvement in outcomes after transcatheter aortic valve replacement. Mediator clusters included demographics, noncardiovascular comorbidities, cardiovascular comorbidities, device-related factors, and nondevice-related procedural factors. Using logistic regression, we serially adjusted for the mediator clusters to examine the contribution of each to the observed improvement in outcomes over time. Among 161 196 patients treated with transcatheter aortic valve replacement at 596 sites, outcomes improved steadily from 2012 to 2018, including 30-day mortality (6.7% to 2.4%), 30-day composite adverse events (25.3% to 10.5%), and 1-year mortality (19.9% to 10.1%; all P<0.001). In sequential models, the unadjusted odds ratio for 30-day mortality was 0.82 per year (95% CI, 0.80-0.84), which was progressively attenuated with addition of each covariate cluster. Most of the improvement was explained by device factors and nondevice procedural factors. Results were similar for 30-day composite adverse events, although the observed temporal improvement was not fully explained by measured factors, suggesting improved technical skill as an additional mediator. In contrast to 30-day outcomes, each cluster of patient and procedural factors contributed similarly to the temporal improvement in 1-year mortality, indicating a greater impact of patient factors on longer-term outcomes. While US patients undergoing transcatheter aortic valve replacement have become younger, healthier, and lower risk over time, the most important factors contributing to improvements in short-term outcomes relate to advances in device technology and procedural factors, whereas changing patient characteristics had a greater impact on improvement in 1-year outcomes.