Formative research to adapt a cardiac rehabilitation program to breast cancer survivors: the heart health after cancer treatment (HEART-ACT) study.

BACKGROUND: Breast cancer survivors are disproportionately at risk for cardiovascular disease; exercise-based interventions may improve cardiovascular health. The objective of this formative research is to better understand the needs of patients and barriers to participation in an adapted cardiac rehabilitation program for diverse breast cancer survivors in an urban safety net setting. METHODS: We recruited 30 participants (10 English-speaking, 10 Spanish-speaking, and 10 Cantonese-speaking) who had received treatment with curative intent for breast cancer from an urban safety net hospital between November 9, 2021, to August 30, 2022. Participants completed surveys and interviews about perspectives on health behaviors and participating in an adapted cardiac rehabilitation program. Interviews were qualitatively analyzed using rapid template analysis with pre-selected constructs from the Theory of Planned Behavior, Unified Theory of Acceptance and Use of Technology, and Consolidated Framework for Implementation Research, as well as emergent codes. We developed a Participant User Journey for a program based on responses and conducted human-centered design sessions with 8 participants to iteratively revise the Participant User Journey. RESULTS: Among 30 participants, mean age was 56.7 years (standard deviation [SD] 10.2) with 100% female sex assigned at birth; 1 participant withdrew before completing study procedures. Most participants had limited health literacy (18/29, 62%). Mean body mass index was 31.4 (SD 8.3), 21/29 (72%) had blood pressure below 140/90 mmHg, and 12/29 (41%) had blood pressure below 130/80. Mean 6-minute walk distance was 384.9 meters (SD 78.3). The desired benefits of a program included healthy living and prevention of cancer recurrence. Barriers to participation included motivation, social support, transportation, and concerns about exercise safety. Participants emphasized the need for practicality, such as fitting physical activity into daily life and nutrition support, including recipes and shopping lists. Trusted experts and cultural and language concordance were viewed as important aspects of the program. CONCLUSIONS: Through participant interviews and human-centered design sessions, we developed the HEART-ACT program, a 12-week multi-disciplinary program addressing physical activity, nutrition, emotional well-being, cardiovascular risk, survivorship, and other components if indicated (e.g., tobacco cessation). Future research will test the effects of this program on patient-centered outcomes.

Cocaine Use is Associated With Increased LVMI in Unstably Housed Women With Polysubstance Use.

BACKGROUND: While substance use is known to influence cardiovascular health, most prior studies only consider one substance at a time. We examined associations between the concurrent use of multiple substances and left ventricular mass index (LVMI) in unhoused and unstably housed women. METHODS: Between 2016 and 2019, we conducted a cohort study of unstably housed women in which measurements included an interview, serum/urine collection, vital sign assessment, and a single transthoracic echocardiogram at baseline. We evaluated independent associations between 39 separate substances confirmed through toxicology and echocardiography-confirmed LVMI. RESULTS: The study included 194 participants with a median age of 53.5 years and a high proportion of women of color (72.6%). Toxicology-confirmed substance use included: 69.1% nicotine, 56.2% cocaine, 28.9% methamphetamines, 28.9% alcohol, 23.2% opioid analgesics, and 9.8% opioids with catecholaminergic effects. In adjusted analysis, cocaine was independently associated with higher LVMI (Adjusted linear effect: 18%; 95% CI 9.9, 26.6). Associations with other substances did not reach levels of significance and did not significantly interact with cocaine. CONCLUSION: In a population of vulnerable women where the use of multiple substances is common, cocaine stands out as having particularly detrimental influences on cardiac structure. Blood pressure did not attenuate the association appreciably, suggesting direct effects of cocaine on LVMI. Routinely evaluating stimulant use as a chronic risk factor during risk assessment and preventive clinical care planning may reduce end organ damage, particularly in highly vulnerable women.

Rate-Adaptive Atrial Pacing for Heart Failure With Preserved Ejection Fraction: The RAPID-HF Randomized Clinical Trial.

Importance: Reduced heart rate during exercise is common and associated with impaired aerobic capacity in heart failure with preserved ejection fraction (HFpEF), but it remains unknown if restoring exertional heart rate through atrial pacing would be beneficial. Objective: To determine if implanting and programming a pacemaker for rate-adaptive atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence. Design, Setting, and Participants: Single-center, double-blind, randomized, crossover trial testing the effects of rate-adaptive atrial pacing in patients with symptomatic HFpEF and chronotropic incompetence at a tertiary referral center (Mayo Clinic) in Rochester, Minnesota. Patients were recruited between 2014 and 2022 with 16-week follow-up (last date of follow-up, May 9, 2022). Cardiac output during exercise was measured by the acetylene rebreathe technique. Interventions: A total of 32 patients were recruited; of these, 29 underwent pacemaker implantation and were randomized to atrial rate responsive pacing or no pacing first for 4 weeks, followed by a 4-week washout period and then crossover for an additional 4 weeks. Main Outcomes and Measures: The primary end point was oxygen consumption (V̇o2) at anaerobic threshold (V̇o2,AT); secondary end points were peak V̇o2, ventilatory efficiency (V̇e/V̇co2 slope), patient-reported health status by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Results: Of the 29 patients randomized, the mean age was 66 years (SD, 9.7) and 13 (45%) were women. In the absence of pacing, peak V̇o2 and V̇o2 at anaerobic threshold (V̇o2,AT) were both correlated with peak exercise heart rate (r = 0.46-0.51, P < .02 for both). Pacing increased heart rate during low-level and peak exercise (16/min [95% CI, 10 to 23], P < .001; 14/min [95% CI, 7 to 21], P < .001), but there was no significant change in V̇o2,AT (pacing off, 10.4 [SD, 2.9] mL/kg/min; pacing on, 10.7 [SD, 2.6] mL/kg/min; absolute difference, 0.3 [95% CI, -0.5 to 1.0] mL/kg/min; P = .46), peak V̇o2, minute ventilation (V̇e)/carbon dioxide production (V̇co2) slope, KCCQ-OSS, or NT-proBNP level. Despite the increase in heart rate, atrial pacing had no significant effect on cardiac output with exercise, owing to a decrease in stroke volume (-24 mL [95% CI, -43 to -5 mL]; P = .02). Adverse events judged to be related to the pacemaker device were observed in 6 of 29 participants (21%). Conclusions and Relevance: In patients with HFpEF and chronotropic incompetence, implantation of a pacemaker to enhance exercise heart rate did not result in an improvement in exercise capacity and was associated with increased adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT02145351.

Association of Right Ventricular Dilation and Dysfunction on Echocardiogram with In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared with Other Acute Respiratory Illness.

Background: Although right ventricular (RV) dysfunction is associated with mortality in acute COVID-19, the role of RV dilation is uncertain. The prognostic significance of RV dilation and dysfunction among hospitalized patients with acute COVID-19 compared to other respiratory illnesses. Methods: We conducted a retrospective cohort study to examine 225 consecutive adults admitted for acute COVID-19 and 6,150 control adults admitted for influenza, pneumonia or ARDS who had a clinical echocardiogram performed. We used logistic regression models to assess associations between RV parameters and in-hospital mortality adjusted for confounders. Results: Among those with COVID-19, 48/225 (21.3%) died during the index hospitalization compared to 727/6150 (11.8%) with other respiratory illness (p=0.001). Independent of COVID-19, mild and moderate to severe RV dilation were associated with 1.4 and 2.0 times higher risk of inpatient mortality, respectively (95%CI 1.17 to 1.69; p=0.0003; 95%CI 1.62 to 2.47; p<0.0001, respectively). Similarly, mild and moderate RV dysfunction were associated with 1.4 and 1.7 times higher risk of inpatient mortality (95%CI 1.10 to 1.77; p=0.007; 95%CI 1.17 to 2.42; p=0.005, respectively). Relative to normal RV size and non-COVID-19 acute respiratory illness, mild and moderate RV dilation were associated with 1.4 times and 2.0 times higher risk among those without COVID-19 and 1.9 times higher and 3.0 times higher risk among those with COVID-19, with similar findings for RV dysfunction. Having both RV dilation and dysfunction or RV dilation alone were associated with 1.7 times higher risk while RV dysfunction alone was associated with 1.4 times higher risk compared to normal RV size and function. Conclusions: RV dilation and dysfunction are associated with increased risk of inpatient mortality among those with COVID-19 and other respiratory illnesses. Abnormal RV findings may identify those at higher risk of short-term mortality from acute respiratory illness including COVID-19 beyond other risk markers.

Early identification of patients with Chagas disease at risk of developing cardiomyopathy using 2-D speckle tracking strain: Win, Miranda prediction of Chagas cardiomyopathy.

Background: Chagas disease is an endemic protozoan disease with high prevalence in Latin America. Of those infected, 20-30% will develop chronic Chagas cardiomyopathy (CCC) however, prediction using existing clinical criteria remains poor. In this study, we investigated the utility of left ventricular (LV) echocardiographic speckle-tracking global longitudinal strain (GLS) for early detection of CCC. Methods and results: 139 asymptomatic T. cruzi seropositive subjects with normal heart size and normal LV ejection fraction (EF) (stage A or B) were enrolled in this prospective observational study and underwent paired echocardiograms at baseline and 1-year follow-up. Progressors were participants classified as stage C or D at follow-up due to development of symptoms of heart failure, cardiomegaly, or decrease in LVEF. LV GLS was calculated as the average peak systolic strain of 16 LV segments. Measurements were compared between participants who progressed and did not progress by two-sample t-test, and the odds of progression assessed by multivariable logistic regression. Of the 139 participants, 69.8% were female, mean age 55.8 ± 12.5 years, with 12 (8.6%) progressing to Stage C or D at follow-up. Progressors tended to be older, male, with wider QRS duration. LV GLS was -19.0% in progressors vs. -22.4% in non-progressors at baseline, with 71% higher odds of progression per +1% of GLS (adjusted OR 1.71, 95% CI 1.20-2.44, p = 0.003). Conclusion: Baseline LV GLS in participants with CCC stage A or B was predictive of progression within 1-year and may guide timing of clinical follow-up and promote early detection or treatment.

Outcomes in Patients With Heart Failure Using Cocaine.

Cocaine is an established cardiovascular toxin, but the impact of cocaine use on clinical outcomes in heart failure (HF) remains unknown. Although nonselective ß-blocker use in cocaine users with HF and reduced ejection fraction (HFrEF) appears to be safely tolerated, selective ß-blockers have not been evaluated. This study aimed to assess whether cocaine use is associated with worse clinical outcomes in patients with HF and evaluate the safety of ß-blocker prescription upon discharge in cocaine users with HFrEF. This was a single-center retrospective cohort study of patients with incident HF hospitalization at a safety-net hospital. Primary outcomes included all-cause mortality and readmissions, including HF. Cocaine users were compared with nonusers matched by age, gender, and year of index admission. In cocaine users with HFrEF, outcomes were compared according to ß-blocker prescription at discharge. From 2001 to 2019, 738 cocaine users were identified and compared with 738 matched nonusers. Cocaine use was associated with increased mortality (adjusted hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.00 to 1.48) and 90-day readmission (all-cause: adjusted HR 1.49; 95% CI 1.20 to 1.85; HF: adjusted HR 1.49; 95% CI 1.10 to 2.01), persisting at 1 year. In cocaine users who were prescribed metoprolol, carvedilol, or no ß-blocker at discharge, the rates of 1-year mortality and 30-day readmission were similar. In conclusion, cocaine use is associated with increased all-cause mortality, HF readmission, and all-cause readmission. Both nonselective and selective ß-blocker may be safe in managing patients with HFrEF and cocaine use.

Role of antibodies, inflammatory markers, and echocardiographic findings in postacute cardiopulmonary symptoms after SARS-CoV-2 infection.

Shortness of breath, chest pain, and palpitations occur as postacute sequelae of COVID-19, but whether symptoms are associated with echocardiographic abnormalities, cardiac biomarkers, or markers of systemic inflammation remains unknown. In a cross-sectional analysis, we assessed symptoms, performed echocardiograms, and measured biomarkers among adults more than 8 weeks after confirmed SARS-CoV-2 infection. We modeled associations between symptoms and baseline characteristics, echocardiographic findings, and biomarkers using logistic regression. We enrolled 102 participants at a median of 7.2 months following COVID-19 onset; 47 individuals reported dyspnea, chest pain, or palpitations. Median age was 52 years, and 41% of participants were women. Female sex, hospitalization, IgG antibody against SARS-CoV-2 receptor binding domain, and C-reactive protein were associated with symptoms. Regarding echocardiographic findings, 4 of 47 participants (9%) with symptoms had pericardial effusions compared with 0 of 55 participants without symptoms; those with effusions had a median of 4 symptoms compared with a median of 1 symptom in those without effusions. There was no strong evidence for a relationship between symptoms and echocardiographic functional parameters or other biomarkers. Among adults more than 8 weeks after SARS-CoV-2 infection, SARS-CoV-2 RBD antibodies, markers of inflammation, and, possibly, pericardial effusions are associated with cardiopulmonary symptoms. Investigation into inflammation as a mechanism underlying postacute sequelae of COVID-19 is warranted.

Prospective arrhythmia surveillance after a COVID-19 diagnosis.

BACKGROUND: Cardiac arrhythmias have been observed among patients hospitalised with acute COVID-19 infection, and palpitations remain a common symptom among the much larger outpatient population of COVID-19 survivors in the convalescent stage of the disease. OBJECTIVE: To determine arrhythmia prevalence among outpatients after a COVID-19 diagnosis. METHODS: Adults with a positive COVID-19 test and without a history of arrhythmia were prospectively evaluated with 14-day ambulatory electrocardiographic monitoring. Participants were instructed to trigger the monitor for palpitations. RESULTS: A total of 51 individuals (mean age 42±11 years, 65% women) underwent monitoring at a median 75 (IQR 34-126) days after a positive COVID-19 test. Median monitoring duration was 13.2 (IQR 10.5-13.8) days. No participant demonstrated atrial fibrillation, atrial flutter, sustained supraventricular tachycardia (SVT), sustained ventricular tachycardia or infranodal atrioventricular block. Nearly all participants (96%) had an ectopic burden of <1%; one participant had a 2.8% supraventricular ectopic burden and one had a 15.4% ventricular ectopic burden. While 47 (92%) participants triggered their monitor for palpitation symptoms, 78% of these triggers were for either sinus rhythm or sinus tachycardia. CONCLUSIONS: We did not find evidence of malignant or sustained arrhythmias in outpatients after a positive COVID-19 diagnosis. While palpitations were common, symptoms frequently corresponded to sinus rhythm/sinus tachycardia or non-malignant arrhythmias such as isolated ectopy or non-sustained SVT. While these findings cannot exclude the possibility of serious arrhythmias in select individuals, they do not support a strong or widespread proarrhythmic effect of COVID-19 infection after resolution of acute illness.

Right Ventricular Strain Predicts Structural Disease Progression in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition associated with ventricular arrhythmias and myocardial dysfunction; however, limited data exist on identifying patients at highest risk. The purpose of the study was to determine whether measures of right ventricular (RV) dysfunction on echocardiogram including RV strain were predictive of structural disease progression in ARVC. Methods and Results A retrospective analysis of serial echocardiograms from 40 patients fulfilling 2010 task force criteria for ARVC was performed to assess structural progression defined by an increase in proximal RV outflow tract dimensions (parasternal short or long axis) or decrease in RV fractional area change. Echocardiograms were analyzed for RV free-wall peak longitudinal systolic strain using 2-dimensional speckle tracking. Risk of structural progression and 5-year change in RV outflow tract measurements were compared with baseline RV strain. Of the 40 ARVC patients, 61% had structural progression with an increase in the mean parasternal short-axis RV outflow tract dimension from 36.2 to 38.5 mm (P=0.022) and 68% by increase in parasternal long-axis RV outflow tract dimension from 36.1 to 39.2 mm (P=0.001). RV fractional area change remained stable over time. Baseline RV strain was significantly associated with the risk of structural progression and 5-year rate of change. Patients with an RV strain more positive than -20% had a higher risk (odds ratio: 18.4; 95% CI, 2.7-125.8; P=0.003) of structural progression. Conclusions RV free wall strain is associated with the rate of structural progression in patients with ARVC. It may be a useful marker in determining which patients require closer follow-up and treatment.

High sustained virologic response in genotypes 3 and 6 with generic NS5A inhibitor and sofosbuvir regimens in chronic HCV in myanmar.

Exclusive HCV therapy clinical trials with genotype 6 patients in high prevalence areas have been sparse. We analysed the safety and efficacy of two generic, pangenotypic NS5A/NS5B combination oral DAA regimens, primarily in genotypes 3 and 6, in a real-world setting: (a) daclatasvir/sofosbuvir (DCV/SOF) ± ribavirin (RBV) and (b) Velpatasvir/sofosbuvir (VEL/SOF ± RBV). Between December 2015 and November 2017, data from 522 patients were analysed, 311 of whom were treated with DCV/SOF ± RBV for 12/24 weeks (genotype 3: n = 193, genotype 6: n = 89) and 211 were treated with VEL/SOF ± RBV for 12/24 weeks (genotype 3: n = 83, genotype 6: n = 77). Overall SVR rates were high for both DCV/SOF ± RBV (96.1%, n = 299/311) and VEL/SOF ± RBV (95.3%, n = 201/211), and there was a good adverse event profile. Treatment naïve status and inclusion of RBV (in advanced fibrosis/cirrhosis) were significant independent predictors of achieving SVR12, while type of DAA regimen was not predictive. In this large cohort of genotypes 3 (n = 276) and 6 (n = 166; n = 127 unique subtype of 6c-l), high SVR rates of 94.9% (n = 262/276) and 95.2% (n = 158/166), respectively, were noted. In conclusion, generic and pangenotypic DCV/SOF and VEL/SOF ± RBV regimens were highly effective and safe, in genotypes 3 and 6 chronic HCV in Myanmar. These efficacious pangenotypic regimens suggest that baseline genotype testing can be eliminated moving forward. While RBV may still be needed for those with advanced fibrosis/cirrhosis, in a global elimination strategy it would not be practical even if it does compromise SVR in a minority with difficult to treat characteristics.

Inpatient Mortality Risk Scores and Postdischarge Events in Hospitalized Heart Failure Patients: A Community-Based Study.

BACKGROUND: The Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines (GWTG) registries have developed simple heart failure (HF) in-hospital mortality risk scores. We hypothesized that HF scores predictive of in-hospital mortality would perform as well for early postdischarge mortality risk stratification. METHODS AND RESULTS: In this single-center, community-based, retrospective study of all consecutive primary HF hospitalizations (6203 hospitalizations in 3745 patients) from 2000 to 2013, the ADHERE and GWTG risk scores were calculated from admission data. There were 176 (3.0%) and 399 (6.7%), 869 (14.7%), and 1272 (21.5%) deaths in-hospital and at 30, 90, and 180 days postdischarge, respectively. The GWTG but not ADHERE risk score was well calibrated for in-hospital mortality. Both the ADHERE (C statistic 0.66 and 0.67, 0.64, and 0.64) and GWTG (C statistic 0.74 and 0.73, 0.71, and 0.70) HF risk scores were similarly predictive of in-hospital and 30-, 90-, and 180-day postdischarge mortality. The ADHERE risk score identified 10% and the GWTG risk score identified 20% of hospitalizations where 180-day postdischarge mortality was 50%, a prognostic bench mark for hospice referral. In contrast, hospitalizations characterized as lowest risk by the ADHERE (57% of hospitalizations; 180-day mortality 16.2%) or GWTG score (20% of hospitalizations; 180-day mortality 8.0%) had substantially lower mortality (odds ratios high versus low risk of 5-8 [ADHERE] and 11-18 [GWTG] across time points; P<0.0001 for all). CONCLUSIONS: The simple ADHERE and GWTG scores stratify hospitalized HF patients for both inpatient and early postdischarge mortality risk, allowing comprehensive risk assessment on admission.

Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients With Heart Failure and Preserved Ejection Fraction: A Report From the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction).

BACKGROUND: In patients with heart failure and preserved ejection fraction, little is known about the characteristics of, and outcomes in, those with and without diabetes mellitus. METHODS: We examined clinical and echocardiographic characteristics and outcomes in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Ejection Fraction) according to history of diabetes mellitus. Cox regression models were used to estimate hazard ratios for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. RESULTS: Overall, 1134 of 4128 patients (27%) had diabetes mellitus. Compared with those without diabetes mellitus, they were more likely to have a history of myocardial infarction (28% versus 22%), higher body mass index (31 versus 29 kg/m2), worse Minnesota Living With Heart Failure score (48 versus 40), higher median N-terminal pro-B-type natriuretic peptide concentration (403 versus 320 pg/mL; all P<0.01), more signs of congestion, but no significant difference in left ventricular ejection fraction. Patients with diabetes mellitus had a greater left ventricular mass and left atrial area than patients without diabetes mellitus. Doppler E-wave velocity (86 versus 76 cm/s; P<0.0001) and the E/e' ratio (11.7 versus 10.4; P=0.010) were higher in patients with diabetes mellitus. Over a median follow-up of 4.1 years, cardiovascular death or heart failure hospitalization occurred in 34% of patients with diabetes mellitus versus 22% of those without diabetes mellitus (adjusted hazard ratio, 1.75; 95% confidence interval, 1.49-2.05), and 28% versus 19% of patients with and without diabetes mellitus died (adjusted hazard ratio, 1.59; confidence interval, 1.33-1.91). CONCLUSIONS: In heart failure with preserved ejection fraction, patients with diabetes mellitus have more signs of congestion, worse quality of life, higher N-terminal pro-B-type natriuretic peptide levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes mellitus on outcomes in heart failure with preserved ejection fraction and whether they are modifiable. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.

The Hospitalization Burden and Post-Hospitalization Mortality Risk in Heart Failure With Preserved Ejection Fraction: Results From the I-PRESERVE Trial (Irbesartan in Heart Failure and Preserved Ejection Fraction).

OBJECTIVES: The aim of this study was to investigate prognosis in patients with heart failure (HF) with preserved ejection fraction and the causes of hospitalization and post-hospitalization mortality. BACKGROUND: Although hospitalizations in patients with HF with preserved ejection fraction are common, there are limited data from clinical trials on the causes of admission and the influence of hospitalizations on subsequent mortality risk. METHODS: Patients (n = 4,128) with New York Heart Association functional class II to IV HF and left ventricular ejection fractions >45% were enrolled in I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction). A blinded events committee adjudicated cardiovascular hospitalizations and all deaths using predefined and standardized definitions. The risk for death after HF, any-cause, or non-HF hospitalization was assessed using time-dependent Cox proportional hazard models. RESULTS: A total of 2,278 patients had 5,863 hospitalizations during the 49 months of follow-up, of which 3,585 (61%) were recurrent hospitalizations. For any-cause hospitalizations, 26.5% of patients died during follow-up, with an incident mortality rate of 11.1 deaths per 100 patient-years (PYs) and an adjusted hazard ratio of 5.32 (95% confidence interval: 4.21 to 6.23). Overall, 53.6% of hospitalizations were classified as cardiovascular and 43.7% as noncardiovascular, with 2.7% not classifiable. HF was the largest single cause of initial (17.6%) and overall (21.1%) hospitalizations, although, after HF hospitalization, a substantially higher proportion of readmissions were due to primary HF causes (40%). HF hospitalization occurred in 685 patients, with 41% deaths during follow-up, an incident mortality rate of 19.3 deaths per 100 PYs. The adjusted hazard ratio was 2.93 (95% confidence interval: 2.40 to 3.57) relative to patients who were not hospitalized for HF and was greater in those with longer durations of hospitalization. There were 1,593 patients with only non-HF hospitalizations, 21% of whom died during follow-up, with an incident mortality rate of 8.7 deaths per 100 PYs and an adjusted hazard ratio of 4.25 (95% confidence interval: 3.27 to 5.32). The risk for death was highest in the first 30 days and declined over time for all hospitalization categories. Patients not hospitalized for HF or for any cause had observed incident mortality rates of 3.8 and 1.3 deaths per 100 PYs, respectively. CONCLUSIONS: In I-PRESERVE, HFpEF patients hospitalized for any reason, and especially for HF, were at high risk for subsequent death, particularly early. The findings support the need for careful attention in the post-discharge time period including attention to comorbid conditions. Among those hospitalized for HF, the high mortality rate and increased proportion of readmissions due to HF (highest during the first 30 days), suggest that this group would be an appropriate target for investigation of new interventions.

History of atrial fibrillation as a risk factor in patients with heart failure and preserved ejection fraction.

BACKGROUND: Atrial fibrillation (AFib) is common in heart failure (HF) with preserved ejection fraction (HFpEF). Current AFib stroke risk prediction models include the presence of HF but do not specifically include HFpEF as a risk factor. Whether a history of AFib should be used to identify patients with HFpEF who are at risk has not been established. METHODS AND RESULTS: Baseline characteristics and outcomes of patients with HFpEF in the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial were analyzed in relation to AFib. At baseline, 1209 (29.3%) had a history of AFib. Of these 557 (13.5%) had history of AFib alone, whereas 670 (16.2%) had both a history and AFib on ECG; 2901 (70.3%) had neither. There were no significant differences in the risk of stroke between the 2 groups with a history of AFib who did or did not have AFib present on baseline ECG. During a median follow-up of 53 months, a fatal or nonfatal stroke occurred in 6.5% (79/1209) patients with history of AFib compared with 3.9% (114/2901) with no AFib. Having a history of AFib was independently associated with higher risk of stroke (hazard ratio, 2.2; 95% confidence interval, 1.6-3.2; P<0.0001) compared with those with no history of AFib. CONCLUSIONS: In patients with HFpEF, a history of AFib was common and independently associated with increased risk of stroke, regardless of whether AFib was present on ECG. Patients with HFpEF and a history of AFib should be considered at risk. Further studies are needed to determine whether this risk can be safely reduced. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT000095238.

HAS-BLED and CHA2DS2-VASc scores as predictors of bleeding and thrombotic risk after continuous-flow ventricular assist device implantation.

BACKGROUND: HAS-BLED and CHA2DS2-VASc scores predict bleeding in patients on anticoagulation and thromboembolic (TE) risk in patients with atrial fibrillation, respectively. We hypothesized that these scores would be predictive of bleeding and TE complications following continuous-flow ventricular assist device (CF-VAD) implantation. METHODS AND RESULTS: Baseline HAS-BLED and CHA2DS2-VASc scores were retrospectively determined for 173 consecutive patients who underwent HeartMate II CF-VAD implantation at a single center from 2005 to 2011. Forty-three patients had bleeding (24.9%) and 22 had TE (12.7%) events over a 290 patient-year follow-up period. The mean ± SD HAS-BLED scores were 2.7 ± 1.0 and 1.9 ± 1.1 (P < .0001) in patients with and without bleeding, respectively. The CHA2DS2-VASc scores were 3.6 ± 1.4 and 2.9 ± 1.5 (P = .03) in patients with and without TE events, respectively. A HAS-BLED score of ≥ 3 was associated with a significantly higher risk of bleeding events compared with a score of <3 (42% vs 15%, respectively; hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.82-6.32; P < .001). A CHA2DS2-VASc score of ≥ 3 was associated with a higher risk of TE events compared with a score of <3 (18% vs 4%, respectively; HR 4.02, 95% CI 1.19-13.6; P = .025). CONCLUSIONS: Baseline HAS-BLED and CHA2DS2-VASc scores of ≥ 3 conferred significantly higher risks of bleeding and TE, respectively, following HeartMate II implantation.

Effect of fixed-dose combination of isosorbide dinitrate and hydralazine on all hospitalizations and on 30-day readmission rates in patients with heart failure: results from the African-American Heart Failure Trial.

BACKGROUND: Fixed-dose combination of isosorbide dinitrate and hydralazine (FDC-I/H) reduced mortality by 43% and death or first hospitalization for heart failure (HF) by 37% in the African-American Heart Failure Trial (A-HeFT). Reduction in mortality makes it difficult to determine the effect on hospitalizations unless the analysis adjusts for death as a competing risk. METHODS AND RESULTS: In A-HeFT, 1050 self-identified black patients with moderate to severe HF were randomized to FDC-I/H or placebo. The effects of FDC-I/H on first and all hospitalizations and 30-day readmission rates were analyzed. Deaths as competing risks were adjusted using Fine-Gray regression and joint models of hospitalizations and mortality. There were 558 all-cause and 251 HF hospitalizations in placebo compared with 435 and 173 hospitalizations in the FDC-I/H group. Adjusting for deaths as a competing risk, the effect of FDC-I/H on the first hospitalization for HF, expressed in hazard ratio (95% confidence interval), was 0.61 (0.47-0.80; P<0.001) and 0.88 (0.72-1.06; P=0.18) on the first all-cause hospitalization. The effect of FDC-I/H on all recurrent hospitalizations for HF was 0.66 (0.52-0.83; P=0.0005), similar to the effect on the first hospitalizations for HF, whereas the effect on all hospitalizations for any cause was 0.75 (0.63-0.91; P=0.003). The 30-day all-cause readmission rate after the first hospitalization for HF was 23.6% (29 of 123) in placebo versus 14.8% (12 of 81) in the FDC-I/H group, but the effect (0.59; 0.30-1.16; P=0.12) in this small subgroup was not significant. CONCLUSIONS: Treatment with FDC-I/H was associated with a substantial reduction in the first and recurrent HF hospitalizations, and in total all-cause hospitalizations, reducing the total burden of costly and distressing hospitalizations. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047775.

A rare nonvalvular left ventricular papillary fibroelastoma: A case report.

Papillary fibroelastomas are benign cardiac tumors with high embolic potential typically found on the valvular surfaces of the heart. Nonvalvular papillary fibroelastomas are exceedingly rare. We report the case of a 66-year-old Caucasian male with acute bilateral basal ganglia infarctions found to have a mass adherent to the left ventricular septum by transesophageal echocardiography. The mass was identified as a rare nonvalvular cardiac papillary fibroelastoma based on echogenicity, pedunculated nature, and typical motion. Tissue characterization by cardiac magnetic resonance imaging demonstrated homogeneously hypo-intense signal on T2 weighted imaging and signal hyperintensity after administration of gadolinium contrast, confirming the fibroelastic nature of the mass. Surgical excision was performed via ventriculotomy and histopathologic examination was pathognomonic of a papillary fibroelastoma. We conclude that transesophageal echocardiography provides high diagnostic certainty in patients with cardiac papillary fibroelastomas and can reliably identify atypical locations of these tumors on nonvalvular surfaces. A multimodality imaging approach is not necessarily indicated in all patients with this condition. LEARNING OBJECTIVE: Papillary fibroelastomas are benign cardiac tumors with high embolic potential typically found on the valvular surfaces of the heart. Nonvalvular papillary fibroelastomas are exceedingly rare. Transesophageal echocardiography readily identifies nonvalvular papillary fibroelastomas based on echogenicity, pedunculated nature, and characteristic motion, and reliably differentiates them from other cardiac masses. A multimodality imaging approach is not indicated in all patients with this condition.

Depressive symptoms, physical inactivity and risk of cardiovascular mortality in older adults: the Cardiovascular Health Study.

BACKGROUND: Depressed older individuals have a higher mortality than older persons without depression. Depression is associated with physical inactivity, and low levels of physical activity have been shown in some cohorts to be a partial mediator of the relationship between depression and cardiovascular events and mortality. METHODS: A cohort of 5888 individuals (mean 72.8 ± 5.6 years, 58% female, 16% African-American) from four US communities was followed for an average of 10.3 years. Self-reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) were assessed annually and self-reported physical activity was assessed at baseline and at 3 and 7 years. To estimate how much of the increased risk of cardiovascular mortality associated with depressive symptoms was due to physical inactivity, Cox regression with time-varying covariates was used to determine the percentage change in the log HR of depressive symptoms for cardiovascular mortality after adding physical activity variables. RESULTS: At baseline, 20% of participants scored above the cut-off for depressive symptoms. There were 2915 deaths (49.8%), of which 1176 (20.1%) were from cardiovascular causes. Depressive symptoms and physical inactivity each independently increased the risk of cardiovascular mortality and were strongly associated with each other (all p < 0.001). Individuals with both depressive symptoms and physical inactivity had greater cardiovascular mortality than those with either individually (p < 0.001, log rank test). Physical inactivity reduced the log HR of depressive symptoms for cardiovascular mortality by 26% after adjustment. This was similar for persons with (25%) and without (23%) established coronary heart disease. CONCLUSIONS: Physical inactivity accounted for a significant proportion of the risk of cardiovascular mortality due to depressive symptoms in older adults, regardless of coronary heart disease status.