The latest medical research on Heart Failure

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Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups: Insights From a New Zealand National Registry.

Circulation. Heart failure

Aotearoa/New Zealand has a multiethnic population. Patients with hypertrophic cardiomyopathy (HCM) are enrolled in the national Cardiac Inherited Diseases Registry New Zealand. Here, we report the characteristics of Cardiac Inherited Diseases Registry New Zealand HCM probands with and without pathogenic or likely pathogenic (P/LP) genetic variants for HCM, and assess genetic testing yield and variant spectrum by self-identified ethnicity.

Probands with HCM and enrolled in Cardiac Inherited Diseases Registry New Zealand who have undergone clinical genetic testing over a 17-year period were included. Clinical data, family history, and genetic test results were analyzed.

Of 336 probands, 121 (36%) were women, 220 (66%) were European ethnicity, 41 (12%) were Māori, 26 (8%) were Pacific people, and 49 (15%) were other ethnicities. Thirteen probands (4%) presented with sudden death and 19 (6%) with cardiac arrest. A total of 134 (40%) had a P/LP variant identified; most commonly in the MYPBC3 gene (60%) followed by the MYH7 gene (24%). A P/LP variant was identified in 27% of Māori or Pacific probands versus 43% European or other ethnicity probands (P=0.022); 16% of Māori or Pacific probands had a variant of uncertain significance identified, compared with 9% of European or other ethnicity probands (P=0.092). Women more often had a P/LP variant identified than men (48% versus 35%; P=0.032), and variant-positive probands were younger at clinical diagnosis than variant of uncertain significance/variant-negative probands (39±17 versus 50±17 years; P<0.001) and more likely to have experienced cardiac arrest or sudden death events over their lifetime (P=0.002).

Carriage of a P/LP variant in HCM probands is associated with presentation at younger age, and cardiac arrest or sudden death events. Māori or Pacific probands were less likely to have a P/LP variant identified than European or other ethnicity probands.

Multi-Ethnic Study of Atherosclerosis Early Heart Failure Study: Rationale, Design, and Baseline Characteristics.

Circulation. Heart failure

Current prevalence estimates of heart failure (HF) are primarily based on self-report or HF hospitalizations. There is an unmet need to define the prevalence and pathogenesis of early symptomatic HF, which may be undiagnosed and precedes HF hospitalization.

The MESA (Multi-Ethnic Study of Atherosclerosis) Early HF study was conducted during MESA exam 6 to determine the prevalence of early HF and investigate the transition from risk factors to early HF in a diverse population-based cohort of older adults. Between 2016 and 2018, 3285 MESA participants from 6 field centers underwent comprehensive speckle-tracking echocardiography with passive leg raise maneuver, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, arterial stiffness assessment, and proteomics (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]).

Median age was 73 (25th-75th percentile 67-81) years, 53.2% were female, 25.6% were Black, 12.8% were Chinese, and 40.0% were White. The prevalence of HF risk factors was high: hypertension, 61.9%; former or current smoking, 53.7%; obesity 34.8%; diabetes; 24.7%; and chronic kidney disease; 22%. Overt cardiovascular disease, which ranged from 2.1% (HF) to 13.6% (atrial fibrillation), was less common. Of the 3285 participants, 96% underwent proteomics, 94% Kansas City Cardiomyopathy Questionnaire, 93% speckle-tracking echocardiography with passive leg raise, 82% arterial stiffness exam, and 77% 6-minute walk test. Feasibility of resting speckle-tracking echocardiography (87%-99% across cardiac chambers) and passive leg raise Doppler/speckle-tracking echocardiography (>84%) measurements was high. A total of 120 unique echocardiographic indices were measured.

The MESA Early HF study is a key resource for cardiovascular researchers who are interested in improving the epidemiological and phenotypic characterization of early HF.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005487.

Impact of Advanced Therapy Centers on Characteristics and Outcomes of Heart Failure Admissions.

Circulation. Heart failure

Although much attention has been paid to admission and transfer patterns for cardiogenic shock, contemporary data are lacking on decompensated heart failure (HF) admissions and transfers and the impact of advanced therapy centers (ATCs) on outcomes.

HF hospitalizations were obtained from the Nationwide Readmissions Database 2016 to 2019. Centers performing at least 1 heart transplant or left ventricular assist device were classified as ATCs. Patient characteristics, outcomes, and procedural volume were compared among 3 cohorts: admissions to non-ATCs, admissions to ATCs, and transfers to ATCs. A secondary analysis evaluated outcomes for severe HF hospitalizations (cardiogenic shock, cardiac arrest, and mechanical ventilation). Multivariable logistic regression was performed to adjust for the presence of HF decompensations and significant clinical variables during univariate analysis.

A total of 2 331 690 hospitalizations (81.2%) were admissions to non-ATCs (94.5% of centers), 525 037 (18.3%) were admissions to ATCs (5.5% of centers), and 15 541 (0.5%) were transferred to ATCs. Patients treated at ATCs (especially those transferred) had higher rates of HF decompensations, procedural frequency, lengths of stay, and costs. Unadjusted mortality was 2.6% at non-ATCs and was higher at ATCs, both for directly admitted (2.9%, P<0.001) and transferred (11.2%, P<0.001) patients. However, multivariable-adjusted mortality was significantly lower at ATCs, both for directly admitted (odds ratio, 0.82 [95% CI, 0.78-0.87]; P<0.001) and transferred (odds ratio, 0.66 [95% CI, 0.57-0.78]; P<0.001) patients. For severe HF admissions, unadjusted mortality was 37.2% at non-ATCs and was lower at ATCs, both for directly admitted (25.3%, P<0.001) and transferred (25.2%, P<0.001) patients, with similarly lower multivariable-adjusted mortality.

Patients with HF treated at ATCs were sicker but associated with higher procedural volume and lower adjusted mortality.

Relationship Between the Mixed Venous-to-Arterial Carbon Dioxide Gradient and Cardiac Index in Acute Pulmonary Embolism.

European Heart Journal

Among patients with acute pulmonary embolism (PE) undergoing mechanical thrombectomy, the cardiac index (CI) is frequently reduced even among those without clinically apparent shock. The purpose of this study was to describe the mixed venous-to-arterial carbon dioxide gradient (CO2 gap), a surrogate of perfusion adequacy, among patients with acute PE undergoing mechanical thrombectomy.

This was a single-center retrospective study of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization over a 3-year period.

Of 107 patients, 97 had simultaneous mixed venous and arterial blood gas measurements available. The CO2 gap was elevated (>6 mmHg) in 51% of the cohort and in 49% of patients with intermediate-risk PE. A reduced CI (≤2.2 L/min/m2) was associated with an increased odds (OR = 7.9; 95% CI 3.49-18.1, p < 0.001) for an elevated CO2 gap. There was an inverse relationship between CI and CO2 gap. For every 1 L/min/m2 decrease in the CI, the CO2 gap increased by 1.3 mmHg (p = 0.001). Among patients with an elevated baseline CO2 gap >6 mmHg, thrombectomy improved CO2 gap, CI, and mixed venous oxygen saturation. When the CO2 gap was dichotomized above and below 6, there was no difference in in-hospital mortality (9% vs. 0%; p = 0.10, HR: 1.24; 95% CI: 0.97-1.60; P = 0.085).

Among patients with acute PE undergoing mechanical thrombectomy, the CO2 gap is abnormal in nearly 50% of patients and inversely related to CI. Further studies should examine the relationship between markers of perfusion and outcomes in this population to refine risk stratification.

Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF.

Circulation. Heart failure

The TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) found no significant difference in all-cause mortality or hospitalization among patients randomized to a strategy of torsemide versus furosemide following a heart failure (HF) hospitalization. However, outcomes and responses to some therapies differ by left ventricular ejection fraction (LVEF). Thus, we sought to explore the effect of torsemide versus furosemide by baseline LVEF and to assess outcomes across LVEF groups.

We compared baseline patient characteristics and randomized treatment effects for various end points in TRANSFORM-HF stratified by LVEF: HF with reduced LVEF, ≤40% versus HF with mildly reduced LVEF, 41% to 49% versus HF with preserved LVEF, ≥50%. We also evaluated associations between LVEF and clinical outcomes. Study end points were all-cause mortality or hospitalization at 30 days and 12 months, total hospitalizations at 12 months, and change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score.

Overall, 2635 patients (median 64 years, 36% female, 34% Black) had LVEF data. Compared with HF with reduced LVEF, patients with HF with mildly reduced LVEF and HF with preserved LVEF had a higher prevalence of comorbidities. After adjusting for covariates, there was no significant difference in risk of clinical outcomes across the LVEF groups (adjusted hazard ratio for 12-month all-cause mortality, 0.91 [95% CI, 0.59-1.39] for HF with mildly reduced LVEF versus HF with reduced LVEF and 0.91 [95% CI, 0.70-1.17] for HF with preserved LVEF versus HF with reduced LVEF; P=0.73). In addition, there was no significant difference between torsemide and furosemide (1) for mortality and hospitalization outcomes, irrespective of LVEF group and (2) in changes in Kansas City Cardiomyopathy Questionnaire clinical summary score in any LVEF subgroup.

Despite baseline demographic and clinical differences between LVEF cohorts in TRANSFORM-HF, there were no significant differences in the clinical end points with torsemide versus furosemide across the LVEF spectrum. There was a substantial risk for all-cause mortality and subsequent hospitalization independent of baseline LVEF.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813.

Metabolomic Association and Risk Prediction With Heart Failure in Older Adults.

Circulation. Heart failure

Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults.

Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication.

Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05).

Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.

Aerobic Exercise Attenuates Pressure Overload-Induced Myocardial Remodeling and Myocardial Inflammation via Upregulating miR-574-3p in Mice.

Circulation. Heart failure

Exercise training can promote cardiac rehabilitation, thereby reducing cardiovascular disease mortality and hospitalization rates. MicroRNAs (miRs) are closely related to heart disease, among which miR-574-3p plays an important role in myocardial remodeling, but its role in exercise-mediated cardioprotection is still unclear.

A mouse myocardial hypertrophy model was established by transverse aortic coarctation, and a 4-week swimming exercise training was performed 1 week after the operation. After swimming training, echocardiography was used to evaluate cardiac function in mice, and histopathologic staining was used to detect cardiac hypertrophy, myocardial fibrosis, and cardiac inflammation. Quantitative real-time polymerase chain reaction was used to detect the expression levels of miR-574-3p and cardiac hypertrophy markers. Western blotting detected the IL-6 (interleukin-6)/JAK/STAT inflammatory signaling pathway.

Echocardiography and histochemical staining found that aerobic exercise significantly improved pressure overload-induced myocardial hypertrophy (n=6), myocardial interstitial fibrosis (n=6), and cardiac inflammation (n=6). Quantitative real-time polymerase chain reaction detection showed that aerobic exercise upregulated the expression level of miR-574-3p (n=6). After specific knockdown of miR-574-3p in mouse hearts with adeno-associated virus 9 using cardiac troponin T promoter, we found that the protective effect of exercise training on the heart was significantly reversed. Echocardiography and histopathologic staining showed that inhibiting the expression of miR-574-3p could partially block the effects of aerobic exercise on cardiac function (n=6), cardiomyocyte cross-sectional area (n=6), and myocardial fibrosis (n=6). Western blotting and immunohistochemical staining showed that the inhibitory effects of aerobic exercise on the IL-6/JAK/STAT pathway and cardiac inflammation were partially abolished after miR-574-3p knockdown. Furthermore, we also found that miR-574-3p exerts cardioprotective effects in cardiomyocytes by targeting IL-6 (n=3).

Aerobic exercise protects cardiac hypertrophy and inflammation induced by pressure overload by upregulating miR-574-3p and inhibiting the IL-6/JAK/STAT pathway.

Ready-to-Eat Food Environments and Risk of Incident Heart Failure: A Prospective Cohort Study.

Circulation. Heart failure

Food environments have been linked to cardiovascular diseases; however, few studies have assessed the relationship between food environments and the risk of heart failure (HF). We aimed to evaluate the association between ready-to-eat food environments and incident HF at an individual level in a large prospective cohort.

Exposure to ready-to-eat food environments, comprising pubs or bars, restaurants or cafeterias, and fast-food outlets, were individually measured as both proximity and density metrics. We also developed a composite ready-to-eat food environment density score by summing the densities of 3 types of food environments. Cox proportional analyses were applied to assess the associations of each single type and the composite food environments with HF risk.

Closer proximity to and greater density of ready-to-eat food environments, particularly for pubs and bars and fast-food outlets (P<0.05 for both proximity and density metric) were associated with an elevated risk of incident HF. Compared with those with no exposure to composite ready-to-eat food environments, participants in the highest density score category had a 16% (8%-25%; P<0.0001) higher risk of HF. In addition, we found significant interactions of food environments with education, urbanicity, and density of physical activity facilities on HF risk (all Pinteraction<0.05); the ready-to-eat food environments-associated risk of HF was stronger among participants who were poorly educated, living in urban areas, and without physical activity facilities.

Exposure to ready-to-eat food environments is associated with a higher risk of incident HF, suggesting the potential importance of minimizing unfavorable food environments in the prevention of HF.

The association of the Sequential Organ Failure Assessment score at intensive care unit discharge with intensive care unit readmission in the cardiac intensive care unit.

European Heart Journal

Unplanned intensive care unit (ICU) readmissions contribute to increased morbidity, mortality, and healthcare costs. The severity of patient illness at ICU discharge may predict early ICU readmission. Thus, in this study, we investigated the association of cardiac ICU (CICU) discharge Sequential Organ Failure Assessment (SOFA) score with unplanned CICU readmission in patients admitted to the CICU.

We retrospectively reviewed the hospital medical records of 4659 patients who were admitted to the CICU from 2012 to 18. Sequential Organ Failure Assessment scores at CICU admission and discharge were obtained. The predictive performance of organ failure scoring was evaluated by using area under the receiver operating characteristic (AUROC) curves. The primary outcome was unplanned CICU readmission. Of the 3949 patients successfully discharged from the CICU, 184 (4.7%) had an unplanned CICU readmission or they experienced a deteriorated condition but died without being readmitted to the CICU (readmission group). The readmission group had significantly higher rates of organ failure in all organ systems at both CICU admission and discharge than the non-readmission group. The AUROC of the discharge SOFA score for CICU readmission was 0.731, showing good predictive performance. The AUROC of the discharge SOFA score was significantly greater than that of either the initial SOFA score (P = 0.020) or the Acute Physiology and Chronic Health Evaluation II score (P < 0.001). In the multivariable regression analysis, SOFA score, overweight or obese status, history of heart failure, and acute heart failure as reasons for ICU admission were independent predictors of unplanned ICU readmission during the same hospital stay.

The discharge SOFA score may identify patients at a higher risk of unplanned CICU readmission, enabling targeted interventions to reduce readmission rates and improve patient outcomes.

In-hospital Prognosis of Acute ST-Elevation Myocardial Infarction in Patients with Recent Recreational Drug use.

European Heart Journal

URL: https://clinicaltrials.gov/ct2/show/NCT05063097.

From April 7 to 22, 2021, recreational drug use was detected prospectively by a systematic urine multidrug test in all consecutive patients admitted for STEMI in 39 ICCUs across France. The primary endpoint was major adverse cardiac events (MACEs) defined by death, resuscitated cardiac arrest, or cardiogenic shock.

Among the 325 patients (age 62 ± 13 years, 79% men), 41 (12.6%) had a positive multidrug test (cannabis: 11.1%, opioids: 4.6%, cocaine: 1.2%, 3,4-Methylenedioxymethamphetamine: 0.6%). Prevalence increased to 34.0% in patients under 50 years of age. Recreational drug users were more frequently men (93% vs. 77%, p = 0.02), younger (50 ± 12 years vs. 63 ± 13 years, p < 0.001), and more active smokers (78% vs. 34%, p < 0.001). During hospitalization, 17 MACEs occurred (5.2%), including 6 deaths (1.8%), 10 cardiogenic shocks (3.1%), and 7 resuscitated cardiac arrests (2.2%). MACEs (17.1% vs. 3.5%, p < 0.001) and ventricular arrhythmia (9.8% vs. 1.4%, p = 0.01) were more frequent in recreational drug users. Use of recreational drugs was associated with more MACEs after adjustment for comorbidities (OR = 13.1; 95%CI: 3.4-54.6).

In patients with STEMI, recreational drug use is prevalent, especially in patients under 50 years of age, and is independently associated with an increase of MACEs with more ventricular arrhythmia.

Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators.

Circulation. Heart failure

Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free mitochondrial DNA.

The Genomic Research Alliance for Transplantation is a multicenter, prospective, longitudinal cohort study. Sequencing was used to quantitate dd-cfDNA and polymerase chain reaction to quantitate cell-free mitochondrial DNA in plasma. AR was defined as ≥2R cellular rejection or ≥1 antibody-mediated rejection. The primary composite outcome was AR, graft dysfunction (left ventricular ejection fraction <50% and decrease by ≥10%), or death.

We included 148 patients (65 Black patients and 83 White patients), median age was 56 years and 30% female sex. The incidence of AR was higher in Black patients compared with White patients (43% versus 19%; P=0.002). Antibody-mediated rejection occurred predominantly in Black patients with a prevalence of 20% versus 2% (P<0.001). After transplant, Black patients had higher levels of dd-cfDNA, 0.09% (interquartile range, 0.001-0.30) compared with White patients, 0.05% (interquartile range, 0.001-0.23; P=0.003). Beyond 6 months, Black patients showed a persistent rise in dd-cfDNA with higher levels compared with White patients. Cell-free mitochondrial DNA was higher in Black patients (185 788 copies/mL; interquartile range, 101 252-422 133) compared with White patients (133 841 copies/mL; interquartile range, 75 346-337 990; P<0.001). The primary composite outcome occurred in 43% and 55% of Black patients at 1 and 2 years, compared with 23% and 27% in White patients, P<0.001. In a multivariable model, Black patient race (hazard ratio, 2.61 [95% CI, 1.35-5.04]; P=0.004) and %dd-cfDNA (hazard ratio, 1.15 [95% CI, 1.03-1.28]; P=0.010) were associated with the primary composite outcome.

Elevated dd-cfDNA and cell-free mitochondrial DNA after heart transplant may mechanistically be implicated in the higher incidence of AR and worse clinical outcomes in Black transplant recipients.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.

The outcomes of patients with septic shock treated with propafenone compared to amiodarone for supraventricular arrhythmias are related to end-systolic left atrial volume.

European Heart Journal

ClinicalTrials.gov Identifier: NCT03029169, registered on 24th of January 2017.

Patients with SVA and a left ventricular ejection fraction ≥35% were randomized to receive intravenous propafenone (70mg bolus followed by 400-840mg/24h) or amiodarone (300mg bolus followed by 600-1800mg/24h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40 ml/m². The subgroup outcomes assessed were survival at ICU discharge, 1-month, 3-months, 6-months, and 12-months.

Propafenone cardioverted earlier (p=0.009) and with fewer recurrences (p=0.001) in the patients without LA enlargement (n=133). Patients with LAVI˂40ml/m2 demonstrated a mortality benefit of propafenone over the follow up of 1-year (Cox regression, HR 0.6 (95% CI 0.4; 0.9), p=0.014). Patients with dilated LA (n=37) achieved rhythm control earlier in amiodarone (p=0.05) with similar rates of recurrences (p=0.5) compared to propafenone. The outcomes for patients with LAVI≥40 ml/m2 were less favourable with propafenone compared to amiodarone at 1-month (HR 3.6 (95% CI 1.03; 12.5), p=0.045) however, it did not reach statistical significance at 1 year (HR 1.9 (95% CI 0.8; 4.4), p=0.138).

Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI≥40 ml/m².