CT Angiography in The Detection of Carotid Body Enlargement in Patients with Hypertension and Heart Failure

Introduction: The carotid body (CB) has previously been found to be enlarged and hyperactive in various disease states such as heart failure (HF), hypertension (HTN), and respiratory disease. Evaluation of CB size in these disease states using imaging has not been performed. The purpose of this case–control study was to compare CB sizes in patients with HF and HTN with those of controls using CT angiography. Methods: A retrospective review was performed on 323 consecutive patients who had neck computed tomography angiography (CTA) exams in 2011. Following extensive review, 17 HF and HTN patients and 14 controls were identified. Two radiologists blinded to the patient disease status made consensus bilateral carotid body (CB) measurements on the CTA exams using a previously described standardized protocol. CB axial cross-sectional areas were compared between HF and HTN cases and controls using a paired t test. Results: The right CB demonstrated a mean cross-sectional area of 2.79 mm2 in HF and HTN patients vs. 1.40 mm2 in controls (p = 0.02). The left CB demonstrated a mean cross-sectional area of 3.13 mm2 in HF and HTN patients vs. 1.53 mm in controls (p = 0.03). Conclusion: Our results provide imaging evidence that the carotid bodies are enlarged in patients with HF and HTN. Our case–control series suggests that this enlargement can be detected on neck CTA

Temporal Trends and Prognosis of Physical Examination Findings in Patients with Acute Decompensated Heart Failure: The ARIC Study Community Surveillance

BACKGROUND: Bedside evaluation of congestion is a mainstay of heart failure (HF) management. Whether detected physical examination signs have changed over time as obesity prevalence has increased in HF populations, or if the associated prognosis differs for HF with reduced or preserved ejection fraction (HFrEF or HFpEF) is uncertain. METHODS: From 2005 to 2014, the ARIC study (Atherosclerosis Risk in Communities) conducted adjudicated hospital surveillance of acute decompensated HF. We analyzed trends in physical examination findings, imaging signs, and symptoms related to congestion, both over time and by obesity class, and associated 28-day mortality risks. RESULTS: Of 24 937 weighted hospitalizations for acute decompensated HF (mean age 75 years, 53% women, 32% Black), 47% had HFpEF. The prevalence of obesity increased from 2005 to 2014 for both HF types. With increasing obesity category, detected edema increased, while jugular venous distension decreased, and rales remained stable. Detected edema also increased over time, for both HF types. Associations between 28-day mortality and individual signs and symptoms of congestion were similar for HFpEF and HFrEF; however, the adjusted mortality risk with all 3 (edema, rales, and jugular venous distension) versus <3 physical examination findings was higher for patients with HFpEF (odds ratio, 2.41 [95% CI, 1.53-3.79]) than HFrEF (odds ratio, 1.30 [95% CI, 0.87-1.93]); P for interaction by HF type =0.02. CONCLUSIONS: In patients hospitalized with acute decompensated HF, detected physical examination findings differ both temporally and by obesity. Combined findings from the physical examination are more prognostic of 28-day mortality for patients with HFpEF than HFrEF

Frequency of hemodynamic response to orthostatic stress in heart failure with reduced ejection fraction, associations with clinical blood pressure

Aim. To assess hemodynamic response to active standing test (AST) with beat-to-beat blood pressure (BP) monitoring, their association with office BP and symptoms of orthostatic intolerance in patients with heart failure (HF).Material and methods. Outpatient HF patients with documented  left ventricular ejection  fraction &lt;40%, followed   up in a HF center  and receiving optimal medical therapy, underwent AST with beat-to-beat  non-invasive BP monitoring.Hemodynamic response was assessed according to the European Federation of Autonomic Societies criteria.Results. The study included 87 patients (mean age, 57±10 years; men, 76%). Normal hemodynamic response to orthostatic stress was observed  in 36 (41,4%) patients. Pathological response prevailed during the first minute of orthostatic stress — initial orthostatic hypotension (OH) (n=29, 33,3%) and delayed BP recovery (n=18, 20,7%).  Classical OH was detected  in 4 (4,6%)  patients. There was no orthostatic hypertension, defined as an increase in systolic BP (SBP) ≥20 mm Hg. According to office BP, hypotension was observed in 19 (21,8%) patients (SBP &lt;90 mm Hg in 4 patients and 90-100 mm Hg in 15), hypertension (SBP &gt;140 mm Hg) in 11 (12,6%) patients. Pathological response to orthostatic stress were more often observed  in office  SBP &gt;140 mm Hg compared  to SBP ≤140 mmHg (90,9% and 53,9%, p=0,020).Orthostatic intolerance was noted in 43 (49,4%) patients and were not associated with the level of office SBP (p=0,398) or pathological responses to orthostatic stress (p=0,758 for initial OH and p=0,248  for delayed  BP recovery).Conclusion. The pathological hemodynamic response in AST with beat-to-beat BP monitoring in ambulatory patients with HF is most often represented  by initial OH and delayed BP recovery associated  with office SBP &gt;140 mmHg. The frequency of symptoms of orthostatic intolerance did not differ between groups depending on the presence of an inadequate response to orthostatic stress

Phenotyping heart failure patients for iron deficiency and use of intravenous iron therapy: data from the Swedish Heart Failure Registry.

AIMS: Iron deficiency (ID) is associated with poor prognosis regardless of anaemia. Intravenous iron improves quality of life and outcomes in patients with ID and heart failure (HF) with reduced ejection fraction (HFrEF). In the Swedish HF registry, we assessed (i) frequency and predictors of ID testing; (ii) prevalence and outcomes of ID with/without anaemia; (iii) use of ferric carboxymaltose (FCM) and its predictors in patients with ID. METHODS AND RESULTS: We used multivariable logistic regressions to assess patient characteristics independently associated with ID testing/FCM use, and Cox regressions to assess risk of outcomes associated with ID. Of 21 496 patients with HF and any ejection fraction enrolled in 2017-2018, ID testing was performed in 27%. Of these, 49% had ID and more specifically 36% had ID-/anaemia-, 15% ID-/anaemia+, 29% ID+/anaemia-, and 20% ID+/anaemia+ (48%, 39%, 13%, 30% and 18% in HFrEF, respectively). Risk of recurrent all-cause hospitalizations was higher in patients with ID regardless of anaemia. Of 1959 patients with ID, 19% received FCM (24% in HFrEF). Important independent predictors of ID testing and FCM use were anaemia, higher New York Heart Association class, having HFrEF, and referral to HF specialty care. CONCLUSION: In this nationwide HF registry, ID testing occurred in only about a quarter of the patients. Among tested patients, ID was present in one half, but only one in five patients received FCM indicating low adherence to current guidelines on screening and treatment

Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real-world data from the Swedish Heart Failure Registry.

BACKGROUND: Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection. OBJECTIVE: In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective)/PARAGON-HF [sacubitril/valsartan effective in mildly reduced ejection fraction (EF)]. METHODS: Outpatients from the Swedish HF Registry (SwedeHF) were analysed. In SwedeHF, EF is recorded as  median as EF ≥ 50%. We assessed 2 scenarios: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) all criteria (literal scenario). RESULTS: Of 37 790 outpatients, 57% had EF < 40%, 24% EF 40-49% and 19% EF ≥ 50%. In the pragmatic scenario, 63% were eligible in EF < 50% (67% for EF < 40% and 52% for 40-49%) and 52% in EF ≥ 40% (52% for EF ≥ 50%). For the literal scenario, 32% were eligible in EF < 50% (38% of EF < 40%, 20% of EF 40-49%) and 22% in EF ≥ 40% (25% for EF ≥ 50%). Eligible vs. noneligible patients had more severe HF, more comorbidities and overall worse outcomes. CONCLUSION: In a real-world HF outpatient cohort, 81% of patients had EF < 50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF < 50% may be reproduced whether or not a higher cut-off for EF is considered

Changes in inferior vena cava area represent a more sensitive metric than changes in filling pressures during experimental manipulation of intravascular volume and tone

AIMS: Remote monitoring of pulmonary artery pressure has reduced heart failure (HF) hospitalizations in chronic HF as elevation of pulmonary artery pressure provides information that can guide treatment. The venous system is characterized by high capacitance, thus substantial increases in intravascular volume can occur before filling pressures increase. The inferior vena cava (IVC) is a highly compliant venous conduit and thus a candidate for early detection of change in intravascular volume. We aimed to compare IVC cross-sectional area using a novel sensor with cardiac filling pressures during experimental manipulation of volume status, vascular tone, and cardiac function. METHODS AND RESULTS: Experiments were conducted in sheep to manipulate volume status (colloid infusion), vascular tone (nitroglycerin infusion) and cardiac function (rapid cardiac pacing). A wireless implantable IVC sensor was validated ex-vivo and in-vivo, and then used to measure the cross-sectional area of the IVC. Right- and left-sided cardiac filling pressures were obtained via right heart catheterization. The IVC sensor provided highly accurate and precise measurements of cross-sectional area in ex-vivo and in-vivo validation. IVC area changes were more sensitive than the corresponding changes in cardiac filling pressures during colloid infusion (p < 0.001), vasodilatation (p < 0.001) and cardiac dysfunction induced by rapid pacing (p ≤ 0.02). CONCLUSIONS: Inferior vena cava area can be remotely and accurately measured in real time with a wireless implantable sensor. Changes in IVC area are more sensitive than corresponding changes in filling pressures following experimental volume loading and fluid redistribution. Additional research is warranted to understand if remote monitoring of the IVC may have advantages over pressure-based monitors in HF

ILK Induces Cardiomyogenesis in the Human Heart

Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A)) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT)). The cardiomyogenic effects of ILK(R211A) and ILK(WT) were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A) and ILK(WT). Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs).In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for transduction of growth factor- and β1-integrin-mediated differentiation signals. Altogether, our data indicate that ILK represents a novel regulatory checkpoint during human cardiomyogenesis