Chris J. Kapelios

Bone mass loss in chronic heart failure is associated with secondary hyperparathyroidism and has prognostic significance

Chronic heart failure (CHF) is associated with increased risk of osteoporosis. We investigated the relationship between severity of CHF and bone loss, underlying pathophysiological mechanisms, and the prognostic significance of bone mass changes in heart failure.

Skeletal muscle microcirculatory abnormalities are associated with exercise intolerance, ventilatory inefficiency, and impaired autonomic control in heart failure

BACKGROUND Several skeletal muscle abnormalities have been identified in patients with chronic heart failure (CHF), including endothelial dysfunction. We hypothesized that skeletal muscle microcirculation, assessed by near-infrared spectroscopy (NIRS), is impaired in CHF patients and is associated with disease severity. METHODS Eighty-three stable patients with mild-moderate CHF (72 males, mean age 54 ± 14 years, body mass index 26.7 ± 3.4 kg/m(2)) and 8 healthy subjects, matched for age, gender and body mass index, underwent NIRS with the vascular occlusion technique and cardiopulmonary exercise testing (CPET) evaluation on the same day. Tissue oxygen saturation (StO(2), %), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured in the thenar muscle by NIRS before, during and after 3-minute occlusion of the brachial artery. Measurements included StO(2), oxygen consumption rate (OCR, %/min) and reperfusion rate (RR, %/min). All subjects underwent a symptom-limited CPET on a cycle ergometer. Measurements included VO(2) at peak exercise (VO(2)peak, ml/kg/min) and anaerobic threshold (VO(2)AT, ml/kg/min), VE/VCO(2) slope, chronotropic reserve (CR, %) and heart rate recovery (HRR(1), bpm). RESULTS CHF patients had significantly lower StO(2) (75 ± 8.2 vs 80.3 ± 6, p < 0.05), lower OCR (32.3 ± 10.4 vs 37.7 ± 5.5, p < 0.05) and lower RR (10 ± 2.8 vs 15.7 ± 6.3, p < 0.05) compared with healthy controls. CHF patients with RR ≥9.5 had a significantly greater VO(2)peak (p < 0.001), VO(2)AT (p < 0.01), CR (p = 0.01) and HRR(1) (p = 0.01), and lower VE/VCO(2) slope (p = 0.001), compared to those with RR <9.5. In a multivariate analysis, RR was identified as an independent predictor of VO(2)peak, VE/VCO(2) slope and HRR(1). CONCLUSIONS Peripheral muscle microcirculation, as assessed by NIRS, is significantly impaired in CHF patients and is associated with disease severity.

Intravenous iron alone is equally effective with the combination of iron and erythropoietin for the treatment of iron-deficiency anemia in advanced heart failure.

To the Editor: The prevalence of anemia in patients with New York Heart Association (NYHA) functional class IV heart failure (HF) approaches 80% ([1][1]). Iron deficiency (ID) has been reported as the cause of anemia in more than 70% of advanced HF patients ([2][2]). The underlying mechanisms of ID

Late-onset right ventricular dysfunction after mechanical support by a continuous-flow left ventricular assist device.

BACKGROUND Right heart failure (RHF) is a serious post-operative complication of left ventricular assist device (LVAD) implantation, with significant morbidity and mortality. Many clinical, hemodynamic and laboratory variables have been shown to have prognostic value for appearance of RHF. We sought to investigate the incidence of new-onset right ventricular dysfunction (RVD) complicating the long-term use of LVADs. METHODS We retrospectively examined all patients supported with a continuous-flow LVAD for >1 year at our center. RESULTS Twenty patients (mean age 54 ± 10 years, 95% men, 60% with ischemic cardiomyopathy, left ventricular ejection fraction 22 ± 6%, pulmonary capillary wedge pressure 23.5 ± 7.5 mm Hg, brain natriuretic peptide [BNP] 1,566 ± 1,536 pg/ml, serum creatinine 1.6 ± 0.64 mg/dl, furosemide dose 643 ± 410 mg/day) underwent long-term mechanical support as destination therapy support with a continuous-flow LVAD (HeartMate II) at our center. During follow-up (1,219 ± 692 days), 9 patients (45%) manifested symptoms and signs of RVD (increase in right atrial pressure [RAP], BNP and daily furosemide dose compared with the early post-operative period). In these patients, RAP was increased by 6.6 ± 2.6 mm Hg and BNP by 526 ± 477 pg/ml, whereas furosemide dose increased by 145 ± 119 mg. The mean and median times of RVD onset were 2.3 ± 1.5 and 2.1 years, respectively, after LVAD implantation (range 0.4 to 4.8 years). Four of these patients (44.4%) demonstrated further deterioration of RV function and died 73 ± 106 days (median 25 days, range 9 to 231 days) after first manifestation of RVD. Comparisons of baseline variables regarding medical history and clinical status did not demonstrate significant differences between the patients with or without RVD, including parameters related to RV function at the time of implantation. CONCLUSIONS Late-onset RVD is a complication of LVAD support, which can manifest several months to years from device implantation. This complication has significant adverse implications with regard to patient outcome. Prognostic factors need to be identified to follow and treat high-risk patients more efficiently.

Current and future applications of the intra-aortic balloon pump.

Purpose of review The intra-aortic balloon pump (IABP) has been used for more than 40 years. Although recommended in a wide variety of clinical settings, most of these indications are not evidence-based. This review focuses on studies challenging these traditional indications and evaluates potentially new applications of intra-aortic counterpulsation. Recent findings Recent studies have failed to confirm an improvement in clinical outcomes conferred by the IABP in patients developing cardiogenic shock after acute myocardial infarction. This issue is in need of further investigations. While conflicting results of several retrospective studies and meta-analyses have been published regarding the performance of the IABP in high-risk percutaneous coronary interventions, it has recently been found to improve the long-term clinical outcomes of patients in whom it was implanted before the procedure. Small, single-center studies have reported the use of the IABP as a bridge to transplantation or candidacy for left-ventricular assist device implantation. The recently reported feasibility and safety of its insertion via the subclavian or axillary arteries will facilitate these applications. Summary The revisiting of available data and the performance of new, thoughtfully designed trials should clarify the proper indications for the IABP.

Prolonged intra-aortic balloon pump support in biventricular heart failure induces right ventricular reverse remodeling

BACKGROUND Right ventricular dysfunction is associated with high morbidity and mortality in candidates for left ventricular assist device (LVAD) implantation or cardiac transplantation. METHODS We examined the effects of prolonged intra-aortic balloon pump (IABP) support on right ventricular, renal and hepatic functions in patients presenting with end-stage heart failure. RESULTS Between March 2008 and June 2013, fifteen patients (mean age = 49.5 years; 14 men) with end-stage systolic heart failure (HF), contraindications for any life saving procedure (conventional cardiac surgery, heart transplantation, LVAD implantation) and right ventricular dysfunction were supported with the IABP. The patients remained on IABP support for a mean of 73 ± 50 days (median 72, range of 13-155). We measured the echocardiographic and hemodynamic changes in right ventricular function, and the changes in serum creatinine and bilirubin concentrations before and during IABP support. Mean right atrial pressure decreased from 12.7 ± 6.5 to 3.8 ± 3.3 (P < 0.001) and pulmonary artery pressure decreased from 35.7 ± 10.6 to 25 ± 8.4 mmHg (P = 0.001), while cardiac index increased from 1.5 ± 0.4 to 2.2 ± 0.7 l/m(2)/min (P = 0.003) and right ventricular stroke work index from 485 ± 228 to 688 ± 237 mmHg × ml/m(2) (P = 0.043). Right ventricular end-diastolic diameter decreased from 34.0 ± 6.5 mm to 27.8 ± 6.2 mm (P < 0.001) and tricuspid annular systolic tissue Doppler velocity increased from 9.6 ± 2.4 cm/s to 11.1 ± 2.3 cm/s (P = 0.029). Serum creatinine and bilirubin decreased from 2.1 ± 1.3 to 1.4 ± 0.6 mg/dl and 2.0 ± 1.0 to 0.9 ± 0.5 mg/dl, respectively (P = 0.002 and P < 0.001, respectively). CONCLUSIONS Prolonged IABP support of patients presenting with end-stage heart failure and right ventricular dysfunction induced significant improvement in right ventricular and peripheral organ function.

Effect of Elevated Reperfusion Pressure on "No Reflow" Area and Infarct Size in a Porcine Model of Ischemia-Reperfusion.

Background: The “no reflow” phenomenon (microvascular obstruction despite restoration of epicardial blood flow) develops postreperfusion in acute myocardial infarction and is associated with poor prognosis. We hypothesized that increased reperfusion pressure may attenuate the no reflow phenomenon, as it could provide adequate flow to overcome the high resistance of the microvasculature within the no reflow zone. Thus, we investigated the effect of modestly elevated blood pressure during reperfusion on the extent of no reflow area and infarct size in a porcine model of ischemia–reperfusion. Methods: Eighteen farm pigs underwent acute myocardial infarction by occlusion of the anterior descending coronary artery for 1 hour, followed by 2 hours of reperfusion. Just prior to reperfusion, animals were randomized into 2 groups: in group 1 (control group, n = 9), no intervention was performed. In group 2 (n = 9), aortic pressure was increased by ∼20% (compared to ischemia) by partial clamping of the ascending aorta during reperfusion. Following 2 hours of reperfusion, animals were euthanized to measure area at risk, infarct size, and area of no reflow. Results: Partial clamping of the ascending aorta resulted in modest elevation of blood pressure during reperfusion. The area at risk did not differ between the 2 groups. The no reflow area was significantly increased in group 2 compared to control animals (50% ± 13% vs 37% ± 9% of the area at risk; P = .04). The infarcted area was significantly increased in group 2 compared to control animals (75% ± 17% vs 52% ± 23% of the area at risk; P = .03). Significant positive correlations were observed between systolic aortic pressure and no reflow area, between systolic aortic pressure and infarcted area and between infarcted area and no reflow area during reperfusion. Conclusions: Modestly elevated blood pressure during reperfusion is associated with an increase in no reflow area and in infarct size in a clinically relevant porcine model of ischemia–reperfusion.

Innate heart regeneration: endogenous cellular sources and exogenous therapeutic amplification

ABSTRACT Introduction: The -once viewed as heretical- concept of the adult mammalian heart as a dynamic organ capable of endogenous regeneration has recently gained traction. However, estimated rates of myocyte turnover vary wildly and the underlying mechanisms of cardiac plasticity remain controversial. It is still unclear whether the adult mammalian heart gives birth to new myocytes through proliferation of resident myocytes, through cardiomyogenic differentiation of endogenous progenitors or through both mechanisms. Areas covered: In this review, the authors discuss the cellular origins of postnatal mammalian cardiomyogenesis and touch upon therapeutic strategies that could potentially amplify innate cardiac regeneration. Expert opinion: The adult mammalian heart harbors a limited but detectable capacity for spontaneous endogenous regeneration. During normal aging, proliferation of pre-existing cardiomyocytes is the dominant mechanism for generation of new cardiomyocytes. Following myocardial injury, myocyte proliferation increases modestly, but differentiation of endogenous progenitor cells appears to also contribute to cardiomyogenesis (although agreement on the latter point is not universal). Since cardiomyocyte deficiency underlies almost all types of heart disease, development of therapeutic strategies that amplify endogenous regeneration to a clinically-meaningful degree is of utmost importance.

HIGH FUROSEMIDE DOSES INCREASE MORTALITY AND MORBIDITY IN STABLE CHRONIC HEART FAILURE: A PROSPECTIVE, RANDOMIZED STUDY

High doses of diuretics have been associated with increased mortality in chronic heart failure (HF). It remains unclear whether the administered dose represents a marker of clinical severity or if diuretics exert a deleterious effect. No evidence -based recommendations regarding their optimal use

Dosing of loop diuretics in chronic heart failure: it's time for evidence

In an article recently published in the European Journal of Heart Failure, Damman et al.1 retrospectively investigated the effect of diuretic dose on renal function and clinical outcomes in patients with chronic heart failure (HF). The authors report an association between higher doses of loop diuretics and adverse prognosis, both in terms of cardiovascular mortality and HF-related hospitalizations. Moreover, they report a more rapid decrease of glomerular filtration rate (GFR) with higher doses of diuretics. These results are in accord with findings of previous studies, including one of our own.2 The authors should be commended on their work, as dosing of diuretics in chronic HF patients has historically been arbitrary rather than evidence-based. The authors discuss the meta-analysis of Faris et al.,3 which, contrary to the findings by Damman et al.,1 suggests that withdrawal of loop diuretics may result in exacerbation of symptoms and an increase in event rates. In our opinion, the four studies included in this meta-analysis are not appropriate for deduction of relevant conclusions. One study excluded patients with HF4 and another excluded patients with left-sided HF.5 In the third study,6 HF was the indication for diuretic use in only 40% of participants and exclusion criteria included the combined therapy with beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, furosemide dose >80 mg per day or a history of acute HF. The last study included exclusively elderly patients, only 23.3% of whom had a history of HF.7 Overall, a loop diuretic was administered . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . to less than 50% of patients across all four studies. Importantly, the aforementioned studies were designed to withdraw and not reduce the dose of diuretics; the latter appears to be the most cautious and clinically appropriate approach. Damman et al.1 insightfully discuss the need for trials randomizing euvolaemic patients with chronic HF to withdrawal or dose reduction of diuretics and highlight the paucity of such prospective, randomized studies. We would like to highlight two recent studies that prospectively investigated reduction of loop diuretic dose in patients with stable chronic HF. McKie et al.8 decreased the dose of furosemide by 50% in 32 stable patients with HF with reduced ejection fraction (HFrEF) of whom 19 had a baseline GFR <60 ml/min.1.73m2. The authors reported that dose reduction was safe and was accompanied by a 19% increase in GFR in the low GFR group. A trend towards decreased plasma renin with dose reduction was also noted in both groups. In a study from our group,9 40 patients with stable chronic HFrEF on high baseline furosemide dose (≥120 mg daily) were randomized to receive either their initial dose or one-third of it. Long-term maintenance of decreased dose was feasible in 95% of the participants. The 1and 2-year survival rates free from HF-related hospitalization or cardiac death were significantly higher in the reduced dose group. Furthermore, the patients in the high diuretic dose group experienced worsening of renal function significantly more often compared with the patients in the reduced dose group. In our opinion, further prospective randomized studies are warranted to determine if systematic reduction of furosemide doses in euvolaemic HF patients can lead to improved clinical outcomes.