Gregory Giamouzis

Impact of Dopamine Infusion on Renal Function in Hospitalized Heart Failure Patients: Results of the Dopamine in Acute Decompensated Heart Failure (DAD-HF) Trial

BACKGROUND Worsening renal function (WRF) and hypokalemia related to diuretic use for acute decompensated heart failure (ADHF) are common and associated with poor prognosis. Low-dose dopamine infusion improves renal perfusion; its effect on diuresis or renal function specifically in ADHF is not known. METHODS AND RESULTS Sixty consecutive ADHF patients (age 75.7 ± 11.2 years; 51.7% female; left ventricular ejection fraction 35.3 ± 12.1%) were randomized, after receiving a 40 mg intravenous furosemide bolus, to either high-dose furosemide (HDF, 20 mg/h continuous infusion for 8 hours) or low-dose furosemide combined with low-dose dopamine (LDFD, furosemide 5 mg/h plus dopamine 5 μg kg(-1) min(-1) continuous infusion for 8 hours). Both strategies were compared for total diuresis, WRF (defined as a rise in serum creatinine of >0.3 mg/dL from baseline to 24 hours), electrolyte balance, and 60-day postdischarge outcomes. Mean hourly excreted urine volume (272 ± 149 mL in HDF vs 278 ± 186 mL in LDFD group; P = .965) and changes in dyspnea score (Borg index: -4.4 ± 2.1 in HDF group vs -4.7 ± 2.0 in LDFD group; P = .575) during the 8 hours of protocol treatment were similar in the two groups. WRF was more frequent in the HDF (n = 9; 30%) than in the LDFD group (n = 2; 6.7%; P = .042). Serum potassium changed from 4.3 ± 0.5 to 3.9 ± 0.4 mEq/L at 24 hours (P = .003) in the HDF group and from 4.4 ± 0.5 to 4.2 ± 0.5 mEq/L at 24 hours (P = .07) in the LDFD group. Length of stay and 60-day mortality or rehospitalization rates (all-cause, cardiovascular, and worsening HF) were similar in the two groups. CONCLUSIONS In ADHF patients, the combination of low-dose furosemide and low-dose dopamine is equally effective as high-dose furosemide but associated with improved renal function profile and potassium homeostasis.

Reframing the association and significance of co‐morbidities in heart failure

Several co‐existing diseases and/or conditions (co‐morbidities) are present in patients with heart failure (HF), with diverse clinical relevance. Multiple mechanisms may underlie the co‐existence of HF and co‐morbidities, including direct causation, associated risk factors, heterogeneity, and independence. The complex inter‐relationship of co‐morbidities and their impact on the cardiovascular system contribute to the features of HF, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). The purpose of this work is to provide an overview of the contribution of major cardiac and non‐cardiac co‐morbidities to HF development and outcomes, in the context of both HFpEF and HFrEF. Accordingly, epidemiological evidence linking co‐morbidities to HF and the effect of prevalent and incident co‐morbidities on HF outcome will be reviewed.

Efficacy and safety of high dose versus low dose furosemide with or without dopamine infusion: The Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) Trial

AIMS The role of low-dose dopamine infusion in patients with acute decompensated heart failure (ADHF) remains controversial. We aim to evaluate the efficacy and safety of high- versus low-dose furosemide with or without low-dose dopamine infusion in this patient population. METHODS AND RESULTS 161 ADHF patients (78 years; 46% female; ejection fraction 31%) were randomized to 8-hour continuous infusions of: a) high-dose furosemide (HDF, n=50, 20mg/h), b) low-dose furosemide and low-dose dopamine (LDFD, n=56, 5mg/h and 5 μg kg(-1)min(-1) respectively), or c) low-dose furosemide (LDF, n=55, furosemide 5mg/h). The main outcomes were 60-day and one-year all-cause mortality (ACM) and hospitalization for HF (HHF). Dyspnea relief (Borg index), worsening renal function (WRF, rise in serum creatinine (sCr) ≥ 0.3mg/dL), and length of stay (LOS) were also assessed. The urinary output at 2, 4, 6, 8, and 24h was not significantly different in the three groups. Neither the ACM at day 60 (4.0%, 7.1%, and 7.2%; P=0.74) or at one year (38.1%, 33.9% and 32.7%, P=0.84) nor the HHF at day 60 (22.0%, 21.4%, and 14.5%, P=0.55) or one year (60.0%, 50.0%, and 47%, P=0.40) differed between HDF, LDFD, and LDF groups, respectively. No differences in the Borg index or LOS were noted. WRF was higher in the HDF than in LDFD and LDF groups at day 1 (24% vs. 11% vs. 7%, P<0.0001) but not at sCr peak (44% vs. 38% vs. 29%, P=0.27). No significant differences in adverse events were noted. CONCLUSIONS In ADHF patients, there were no significant differences in the in-hospital and post-discharge outcomes between high- vs. low-dose furosemide infusion; the addition of low-dose dopamine infusion was not associated with any beneficial effects.

Diabetic cardiovascular autonomic neuropathy: clinical implications

Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.

Depression in Patients with Cardiovascular Disease

It has been widely suggested that depression negatively affects patients with cardiovascular disease. There are several pathophysiological mechanisms as well as behavioral processes linking depression and cardiac events. Improvements in nursing and medical care have prolonged survival of this patient population; however, this beneficial outcome has led to increased prevalence of depression. Since mortality rates in chronic heart failure patients remain extremely high, it might be as equally important to screen for depression and there are several valid and reliable screening tools that healthcare personnel could easily employ to identify patients at greater risk. Consultation should be provided by a multidisciplinary team, consisting of cardiologists, psychiatrists, and hospital or community nurses so as to carefully plan, execute, and evaluate medical intervention and implement lifestyle changes. We aim to systematically review the existing knowledge regarding current definitions, prognostic implications, pathophysiological mechanisms, and current and future treatment options in patients with depression and cardiovascular disease, specifically those with heart failure.

Increased number of circulating progenitor cells after implantation of ventricular assist devices.

BACKGROUND Bone marrow-derived circulating progenitor cells possess tissue repair potential, improving perfusion, left ventricular remodeling, and contractility in experimental models. We quantified and investigated the kinetics of 4 circulating progenitor cell sub-populations on the basis of CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR-2) antigen expression. METHODS CD34+, CD34+/CD133+/VEGFR-2-, CD34+/CD133+/VEGFR-2+, and CD34+/CD133-/VEGFR-2+ cells were counted in 10 male patients with end-stage congestive heart failure. Five underwent left ventricular/biventricular assist device (LVAD/BiVAD) implantation (VAD group), and 5 were ineligible for VAD implantation (no-VAD group). Peripheral blood was collected at 3 time points for each patient: before, 15, and 60 days after VAD placement in the VAD group and at the same time points in the no-VAD group. Purified CD34+ cells were stained with anti-CD34, anti-CD133, and anti-VEGFR-2 monoclonal antibodies and analyzed by flow cytometry. Serum levels of granulocyte-colony stimulating factor (G-CSF), interleukin-8, vascular endothelial growth factor-alpha (VEGF-alpha), and B-type natriuretic peptide (BNP) were also measured. RESULTS In the VAD group the number of CD34+ cells/ml of blood tended to increase, from 159.6 +/- 137.0 at baseline to 428.9 +/- 224.3 at 15 days, and decreased to 343.8 +/- 165.7 at 60 days (p = 0.05 vs no-VAD group). In the other 3 cell populations, no significant differences occurred over time or between groups. A significant interaction between BNP levels and VAD status was observed (p = 0.005): BNP levels decreased over time in VAD patients vs no-VAD patients. G-CSF levels tended to decrease over time in both groups, but without a significant difference (p = 0.3). Serum levels of interleukin-8 and VEGF-alpha over time or between VAD and no-VAD patients were not significantly different. CONCLUSIONS After VAD implantation, a transient increase occurs in the number of circulating CD34+ cells, in parallel to a reduction in BNP levels. Release of these cells from the bone marrow may contribute to the improvement of tissue perfusion and cardiac recovery occasionally seen after VAD placement.

The medical and socioeconomic burden of heart failure: A comparative delineation with cancer

Cardiovascular disease and cancer represent the two leading causes of death in the Western World. Still, cardiovascular disease causes more deaths and more hospitalizations than cancer. Although mortality rates of both conditions are generally declining, this is not true for heart failure (HF). The prevalence of HF is increasing, although its incidence has been stabilized, mainly because of the population aging. The survival of patients with HF is overall worse than those with cancer. In addition, HF failure is the most common reason for hospitalization in the elderly, while hospitalization for HF is followed by adverse prognosis and represents the main contributor to the huge financial expenditure caused by the syndrome. The outcome of HF patients and thus its medical and socioeconomic burden may be improved by the more efficient in-hospital management of patients, the enhancement of adherence to guideline-recommended therapies, the identification and treatment of comorbid conditions and the introduction of more effective medical therapies.

Bacterial and fungal microflora in surgically removed lung cancer samples

BackgroundClinical and experimental data suggest an association between the presence of bacterial and/or fungal infection and the development of different types of cancer, independently of chemotherapy-induced leukopenia. This has also been postulated for the development of lung cancer, however the prevalence and the exact species of the bacteria and fungi implicated, have not yet been described.AimTo determine the presence of bacterial and fungal microflora in surgically extracted samples of patients with lung cancer.Materials and methodsIn this single-center prospective, observational study, tissue samples were surgically extracted from 32 consecutive patients with lung cancer, and reverse-transcription polymerase chain reaction (RT-PCR) was used to identify the presence of bacteria and fungi strains.ResultsThe analysis of the electrophoresis data pointed out diversity between the samples and the strains that were identified. Mycoplasma strains were identified in all samples. Strains that appeared more often were Staphylococcus epidermidis, Streptococcus mitis and Bacillus strains, followed in descending frequency by Chlamydia, Candida, Listeria, and Haemophilus influenza. In individual patients Legionella pneumophila and Candida tropicalis were detected.ConclusionsA diversity of pathogens could be identified in surgically extracted tissue samples of patients with lung cancer, with mycoplasma strains being present in all samples. These results point to an etiologic role for chronic infection in lung carcinogenesis. Confirmation of these observations and additional studies are needed to further characterize the etiologic role of inflammation in lung carcinogenesis.

The cardiorenal syndrome in heart failure: cardiac? renal? syndrome?

There has been increasing interest on the so-called cardiorenal syndrome (CRS), defined as a complex pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other. In this review, we contend that there is lack of evidence warranting the adoption of a specific clinical construct such as the CRS within the heart failure (HF) syndrome by demonstrating that: (a) the approaches and tools regarding the definition of kidney involvement in HF are suboptimal; (b) development of renal failure in HF is often confounded by age, hypertension, and diabetes; (c) worsening of renal function (WRF) in HF may be largely independent of alterations in cardiac function; (d) the bidirectional association between HF and renal failure is not unique and represents one of the several such associations encountered in HF; and (e) inflammation is a common denominator for HF and associated noncardiac morbidities. Based on these arguments, we believe that dissecting one of the multiple bidirectional associations in HF and constructing the so-called cardiorenal syndrome is not justified pathophysiologically. Fully understanding of all morbid associations and not only the cardiorenal is of great significance for the clinician who is caring for the patient with HF.

Renal dysfunction in heart failure.

Renal dysfunction is a common, important comorbidity in patients with both chronic and acute heart failure (HF). Chronic kidney disease and worsening renal function (WRF) are associated with worse outcomes, but our understanding of the complex bidirectional interactions between the heart and kidney remains poor. When addressing these interactions, one must consider the impact of intrinsic renal disease resulting from medical comorbidities on HF outcomes. WRF may result from any number of important processes. Understanding the role of each of these factors and their interplay are essential in understanding how to improve outcomes in patients with renal dysfunction and HF.