Parta Hatamizadeh

Clinical Profile and Predictors of Complications in Peripartum Cardiomyopathy

BACKGROUND Clinical profile and predictors of major adverse events (MAE) associated with peripartum cardiomyopathy (PPCM) have not been characterized. METHODS AND RESULTS A retrospective review and analysis of clinical data of 182 patients with PPCM. Forty-six patients had >or=1 MAE, including death (13), heart transplantation (11), temporary circulatory support (4), cardiopulmonary arrest (6), fulminant pulmonary edema (17), thromboembolic complications (4), and defibrillator or pacemaker implantation (10). Diagnosis of PPCM was delayed >or=1 week in 48% of patients with MAE that preceded the diagnosis in 50% of these patients. Seven (32%) of the surviving patients who had MAE and did not undergo heart transplantation had residual brain damage. Significant predictors of MAE were: left ventricular ejection fraction <or=25% (HR 4.20, CI 2.04-8.64) and non-Caucasian background(HR 2.16, CI 1.17- 3.97). These predictors in addition to diagnosis delay (HR 5.51, CI 1.21-25.04) were also associated with death or heart transplantation. CONCLUSIONS 1. PPCM may be associated with mortality or severe and lasting morbidity. 2. Incidence of MAE is higher in non-Caucasians and in women with left ventricular ejection fraction <or=25%. 3. Diagnosis of PPCM is often delayed and preceded by MAE. 4. Increased awareness of PPCM is required for early diagnosis and aggressive therapy in an attempt to prevent complications.

Renal Vasodilatory Action of Dopamine in Patients With Heart Failure Magnitude of Effect and Site of Action

Background— A “renal dose” of dopamine is often used to increase renal blood flow; however, data on the magnitude of effect and site of action in patients with heart failure are scarce. Methods and Results— Renal effects of intravenous dopamine (1, 2, 3, 5, and 10 &mgr;g · kg−1 · min−1) were evaluated in 13 patients with chronic heart failure. Renal blood flow was calculated from renal artery cross-sectional area measured with intravascular ultrasound and renal blood flow velocity-time integral measured by the intravascular Doppler technique. Cross-sectional area increased and was significantly higher than baseline (0.30±0.04 cm2) at 5 &mgr;g · kg−1 · min−1 (0.36±0.05 cm2) and 10 &mgr;g · kg−1 · min−1 (0.38±0.06 cm2). The velocity-time integral was significantly higher than baseline (22±3 cm) at doses of 3 and 5 &mgr;g · kg−1 · min−1 (both 31±4 cm). Renal blood flow increased, whereas renal vascular resistance decreased, reaching statistical significance at 2 &mgr;g · kg−1 · min−1 through 10 &mgr;g · kg−1 · min−1. Cardiac output gradually increased, reaching statistical significance at doses of 5 and 10 &mgr;g · kg−1 · min−1 (5.5±0.5 and 6.1±0.7 versus 4.5±5.2 L/min at baseline), but the increase in renal blood flow appeared proportionately larger than corresponding increases in cardiac output. Conclusions— Dopamine is associated with an increase in renal blood flow in patients with heart failure. This effect is due to dilation of both the large conductance and small resistance renal blood vessels. Further evaluation of the efficacy and safety of dopamine for improvement of renal function in hospitalized patients with heart failure is warranted.

Cardiorenal syndrome: pathophysiology and potential targets for clinical management

Combined dysfunction of the heart and the kidneys, which can be associated with haemodynamic impairment, is classically referred to as cardiorenal syndrome (CRS). Cardiac pump failure with resulting volume retention by the kidneys, once thought to be the major pathophysiologic mechanism of CRS, is now considered to be only a part of a much more complicated phenomenon. Multiple body systems may contribute to the development of this pathologic constellation in an interconnected network of events. These events include heart failure (systolic or diastolic), atherosclerosis and endothelial cell dysfunction, uraemia and kidney failure, neurohormonal dysregulation, anaemia and iron disorders, mineral metabolic derangements including fibroblast growth factor 23, phosphorus and vitamin D disorders, and inflammatory pathways that may lead to malnutrition–inflammation–cachexia complex and protein–energy wasting. Hence, a pathophysiologically and clinically relevant classification of CRS based on the above components would be prudent. With the existing medical knowledge, it is almost impossible to identify where the process has started in any given patient. Rather, the events involved are closely interrelated, so that once the process starts at a particular point, other pathways of the network are potentially activated. Current therapies for CRS as well as ongoing studies are mostly focused on haemodynamic adjustments. The timely targeting of different components of this complex network, which may eventually lead to haemodynamic and vascular compromise and cause refractoriness to conventional treatments, seems necessary. Future studies should focus on interventions targeting these components.

Vasodilators in the management of acute heart failure.

Recent guidelines by the Heart Failure Society of America have recommended consideration for use of nitroprusside, nitroglycerin, or nesiritide in addition to diuretics to achieve hemodynamic and symptomatic improvement. This article reviews the results of previous studies evaluating the pharmacologic and clinical effects and safety profiles of these drugs in patients with heart failure.

Association of malnutrition–inflammation complex and responsiveness to erythropoiesis-stimulating agents in long-term hemodialysis patients

BACKGROUND Protein-energy wasting, inflammation and refractory anemia are common in long-term hemodialysis patients. A decreased responsiveness to erythropoiesis-stimulating agents (ESA) is often the cause of the refractory anemia. We hypothesized that the malnutrition-inflammation complex is an independent predictor of decreased responsiveness to ESAs in hemodialysis patients. METHODS This cohort study of 754 hemodialysis patients was examined for an association between inflammatory and nutritional markers, including the malnutrition-inflammation score (MIS) and responsiveness to ESA. Cubic spline models were fitted to verify found associations. RESULTS The mean (±SD) age of patients was 54 ± 15 years, 53% were diabetic and 32% blacks. MIS was worse in the highest quartile of ESAs responsiveness index (ERI, ESA dose divided by hemoglobin) when compared with 1st quartile (6.5 ± 4.5 versus 4.4 ± 3.4; P < 0.001). Both C-reactive protein (log CRP) (β = 0.19) and interleukin-6 (log IL-6) (β = 0.32) were strong and independent predictors of ERI using multivariate linear regression. Serum albumin (β = -0.30) and prealbumin levels (β = -0.14) were inversely associated with ERI. Each 1 SD higher MIS, higher CRP and lower albumin were associated with 86, 44 and 97% higher likelihood of having highest versus three lowest ERI quartiles in fully adjusted models [odds ratio (and 95% confidence interval) of 1.86 (1.31-2.85), 1.44 (1.08-1.92) and 1.97 (1.41-2.78)], respectively. Cubic splines confirmed the continuous and incremental nature of these associations. CONCLUSIONS Malnutrition-inflammation complex is an incremental predictor of poor responsiveness to ESAs in hemodialysis patients. Further studies are needed to assess whether modulating inflammatory or nutritional processes can improve anemia management.

Recipient-related predictors of kidney transplantation outcomes in the elderly

It is not clear whether in old people with end‐stage renal disease kidney transplantation is superior to dialysis therapy.

Assessment of Renal Hemodynamic Effects of Nesiritide in Patients With Heart Failure Using Intravascular Doppler and Quantitative Angiography

OBJECTIVES We evaluated the magnitude and site of action of the nesiritide mediated renal vasodilatory effect in patients with heart failure (HF). BACKGROUND Nesiritide, a recombinant human B-type natriuretic peptide is approved for the treatment of acute decompensated HF and has been shown to exert favorable hemodynamic, neurohormonal, and symptomatic effects. The renal effect of nesiritide in HF patients has not been well defined. METHODS In 15 patients with acute decompensated HF, intravascular Doppler and quantitative angiography of the renal artery were used to assess the effect of nesiritide on renal artery diameter and velocity time integral as well as renal blood flow and vascular resistance. Nesiritide was administered intravenously at a standard dose of 2 microg/kg bolus followed by a continuous infusion at a rate of 0.01 microg/kg/min. Assessment of nesiritide effect was made at 15 min. RESULTS Nesiritide infusion was associated with a significant central hemodynamic effect including a fall in mean pulmonary artery pressure (36 +/- 12 mm Hg to 31 +/- 13 mm Hg, p < 0.001), mean pulmonary capillary wedge pressure (21 +/- 2 mm Hg to 15 +/- 10 mm Hg, p < 0.001), and systemic vascular resistance (1,995 +/- 532 dynes s cm(-5) to 1,563 +/- 504 dynes s cm(-5), r < 0.001), and an increase in cardiac output from 3.9 +/- 1.2 l/min to 4.6 +/- 1.6 l/min (p = 0.001). Nesiritide was also associated with a significant vasodilatory effect on the large conductance renal arteries resulting in an increase in renal artery diameter from 6.2 +/- 0.7 mm to 6.7 +/- 0.8 mm (p < 0.001). At the same time, there was a concomitant fall in mean renal artery pressure (99 +/- 17 mm Hg to 89 +/- 13 mm Hg, p = 0.002) and renal blood flow velocity time integral (27 +/- 15 cm/beat to 23 +/- 15 cm/beat, p = 0.008) and, therefore, no significant change in renal blood flow or renal vascular resistance. CONCLUSIONS The nesiritide effect on the renal circulation in patients with HF is complex, with a marked vasodilatory action on the large, conductance renal arteries but a concomitant fall in velocity time integral and no effect on renal vascular resistance or renal blood flow. Lack of increase in renal blood flow may be due to a fall in renal blood pressure or an intrarenal vasoconstrictive effect.

Variable Response of Conductance and Resistance Coronary Arteries to Endothelial Stimulation in Patients With Heart Failure Due to Nonischemic Dilated Cardiomyopathy

Attenuation of endothelial-dependent coronary vasodilation has been reported in idiopathic dilated cardiomyopathy and anatomically normal coronaries; however, data are insufficient for understanding the incidence and extent of this finding. The response of conductance and resistance coronary arteries to endothelial stimulation with acetylcholine was examined in 25 patients. Coronary blood flow had a variable response to acetylcholine and suggested coronary endothelial dysfunction in approximately half of the patients. Abnormal endothelial dysfunction involved the large conductance epicardial coronary arteries and the small resistance vessels. Abnormal endothelial response of coronary blood flow to acetylcholine could not be predicted by demographic and hemodynamic data. Conclusions: Coronary artery endothelial function is heterogeneous in patients with idiopathic dilated cardiomyopathy. Endothelial dysfunction is present in approximately half of the cases and involves both resistance as well as conductance coronary blood vessels. Furthermore, coronary endothelial function cannot be predicted by demographic and hemo-dynamic parameters or left ventricular ejection fraction.

Iron indices and survival in maintenance hemodialysis patients with and without polycystic kidney disease

BACKGROUND Anemia is less prominent in patients with polycystic kidney disease (PKD). Such iron indices as ferritin and transferrin saturation (TSAT) values are used to guide management of anemia in individuals on maintenance hemodialysis (MHD). Optimal levels of correction of anemia and optimal levels of TSAT and ferritin are unclear in chronic kidney disease patients and have not been studied specifically in PKD. METHODS We studied 2969 MHD patients with and 128 054 patients without PKD from 580 outpatient hemodialysis facilities between July 2001 and June 2006. Using baseline, time-dependent and time-averaged values with unadjusted and multivariable adjusted analysis models, the survival predictabilities of TSAT and ferritin were studied. RESULTS PKD patients were 58 ± 13 years old and included 46% women, whereas non-PKD patients were 62 ± 15 years old and 45% women. In both PKD and non-PKD patients, a time-averaged TSAT between 30 and 40% was associated with the lowest mortality. Time-averaged ferritin between 100 and <800 ng/mL was associated with the lowest mortality in PKD patients, although this range was 500 to <800 ng/mL in non-PKD patients. CONCLUSIONS In MHD patients with and without PKD, there was a U-shaped relationship between the average TSAT and mortality, and a TSAT of 30-40% was associated with the best survival. However, an average ferritin of 100-800 ng/mL was associated with the best survival in PKD patients, whereas that of non-PKD patients was 500-800 ng/mL. Further studies in PKD and non-PKD patients are necessary to determine whether or not therapeutic attempts to keep TSAT and ferritin levels in these ranges will improve survival.

Association of coronary artery calcium score and vascular dysfunction in long-term hemodialysis patients

Long‐term hemodialysis patients are prone to an exceptionally high burden of cardiovascular disease and mortality. The novel temperature‐based technology of digital thermal monitoring (DTM) of vascular reactivity appears associated with the severity of coronary artery disease in asymptomatic population. We hypothesized that in hemodialysis patients, the DTM and coronary artery calcium (CAC) score have a gradient association that follows that of subjects without kidney disease. We examined the cross‐sectional DTM‐CAC associations in a group of long‐term hemodialysis patients, and their 1:1 matched normal counterpart. Area under the curve for temperature (TMP‐AUC), the surrogate of the DTM index of vascular function, was assessed after a 5‐minute arm‐cuff reactive hyperemia test. Coronary calcium score was measured via electron beam computed tomography or multidetector computed tomography scan. We studied 105 randomly recruited hemodialysis patients (age: 58 ± 13 years, 47% men) and 105 age‐ and gender‐matched controls. In hemodialysis patients vs. controls, TMP‐AUC was significantly worse (114 ± 72 vs. 143 ± 80, P = 0.001) and CAC score was higher (525 ± 425 vs. 240 ± 332, P < 0.001). Hemodialysis patients were 14 times more likely to have CAC score >1000 as compared with controls. After adjustment for known confounders, the relative risk for case vs. control for each standard deviation decrease in TMP‐AUC was 1.46 (95% confidence interval: 1.12–1.93, P = 0.007). Vascular reactivity measured via the novel DTM technology is incrementally worse across CAC scores in hemodialysis patients, in whom both measures are even worse than their age‐ and gender‐matched controls. The DTM technology may offer a convenient and radiation‐free approach to risk‐stratify hemodialysis patients.