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Rodney H Falk

Publications and source records attributed to Rodney H Falk.

At least 19 recordsLinked to original sources
PubMed2005

Is elevated plasma B-natriuretic peptide in amyloidosis simply a function of the presence of heart failure?

This study sought to determine plasma levels of B-natriuretic peptide (BNP) in patients with light-chain-associated amyloidosis and correlate them with the presence or absence of heart failure (HF) and the presence or absence of echocardiographic abnormalities. Patients with normal echocardiographic results had significantly lower BNP levels than those with echocardiographic features of cardiac amyloidosis, whereas BNP levels in the group with HF did not differ from those in patients with asymptomatic cardiac amyloidosis. This observation supports previous observations, suggesting that the elevation of BNP in cardiac amyloidosis may be due not only to elevated ventricular filling pressure but also to direct myocyte damage due to extracellular deposits of amyloid.

Amyloidosis↗
PubMed2005

Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis.

BACKGROUND: Small deposits of amyloid are often found in the hearts of elderly patients. However, extensive deposition of transthyretin-derived amyloid fibrils in the heart (senile systemic amyloidosis [SSA]) can cause heart failure. The clinical features of SSA that involve the heart are ill defined, and the condition may be overlooked as a cause of heart failure. We sought to better define the clinical, echocardiographic, and electrocardiographic features of cardiac involvement in SSA and to compare them with the findings in patients with light chain-associated (AL) amyloidosis that affects the heart. METHODS: Eighteen consecutive patients with SSA and heart failure evaluated at a tertiary referral center for the diagnosis and treatment of amyloidosis were compared with 18 randomly selected patients with AL amyloidosis that involved the heart. All patients underwent a complete clinical and biochemical evaluation. Echocardiograms and electrocardiograms were interpreted by blinded investigators. RESULTS: Patients with SSA were older than those with AL amyloidosis and were all male. Proteinuria (protein output of >1 g per 24 hours) was common in AL amyloidosis but was not present in SSA. Left ventricular wall thickness was greater in patients with SSA than those with AL amyloidosis, but despite thicker walls and older age, the severity of heart failure was less in the SSA group and the median survival was much longer (75 vs 11 months; P = .003). CONCLUSIONS: Senile systemic amyloidosis is a disorder of elderly men and is characterized by amyloidosis clinically limited to the heart. In contrast to the rapid progression of heart failure in AL amyloidosis, SSA results in slowly progressive heart failure. The difference in survival, despite evidence of more myocardial disease in the senile group, suggests that heart failure in AL amyloidosis may have a toxic component, possibly related to the circulating monoclonal light chain.

Adult↗
PubMed2005

Comparison of the strain Doppler echocardiographic features of familial amyloid polyneuropathy (FAP) and light-chain amyloidosis.

Previous work has demonstrated that familial amyloid polyneuropathy (FAP) and light-chain amyloidosis with similar degrees of cardiac involvement cannot be distinguished by standard echocardiographic parameters, yet the severity of congestive heart failure and cardiac mortality is much less in FAP. It was therefore hypothesized that strain and strain-rate imaging, sensitive markers of longitudinal systolic dysfunction, might detect a difference in left ventricular function between FAP and light-chain amyloidosis that could account for the clinical differences.

Amyloid Neuropathies, Familial↗
PubMed2005

Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004.

We undertook this study to develop uniformly accepted criteria for the definition of organ involvement and response for patients on treatment protocols for immunoglobulin light-chain amyloidosis (AL). A consensus panel was convened comprising 13 specialists actively involved in the treatment of patients with amyloidosis. Institutional criteria were submitted from each, and a consensus was developed defining each organ involved and the criteria for response. Specific criteria have been developed with agreed on definitions of organ and hematologic response as a result of discussions at the 10th International Symposium on Amyloid and Amyloidosis held in Tours, France, April 2004. These criteria now form the working definition of involvement and response for the purposes of future data collection and reporting. We report criteria that centers can now use to define organ involvement and uniform response criteria for reporting outcomes in patients with light-chain AL.

Amyloid↗
PubMed2005

Quantitative serum free light chain assay in the diagnostic evaluation of AL amyloidosis.

We compared a new serum immunoassay for quantitation of serum free light chains (FLC) with the conventional tests for clonal immunoglobulin production: bone marrow immunohistochemistry, serum immunofixation electrophoresis, and urine immunofixation electrophoresis. Serum samples from 169 patients with AL amyloidosis and 20 controls were examined. Elevated levels of kappa-FLC and lambda-FLC were found in 94% and 93% of patients with the respective clonal disease. However, false positive elevations of kappa-FLC and lambda-FLC were found in 30% and 44% of patients with clonal disease of the other light chain subtype. We found that the FLC level was a reliable test for the diagnosis of clonal disease when the FLC kappa:lambda ratio was abnormal and was comparable to the conventional tests in patients with AL amyloidosis. After a histologic tissue diagnosis of amyloidosis, determining the type as AL amyloidosis relies on a panel of hematologic tests to determine light chain clonality and the exclusion other forms of amyloidosis.

Adult↗
PubMed2004

Improvement in quality of life of patients with AL amyloidosis treated with high-dose melphalan and autologous stem cell transplantation.

Treatment of AL amyloidosis patients with high-dose melphalan chemotherapy followed by autologous peripheral blood stem cell transplantation (HDM/SCT) can produce hematologic complete responses (CRs) and improvement in organ function. To determine whether these responses are accompanied by improvement in quality of life (QOL), we employed the Medical Outcomes Study (MOS) 36-item Short Form General Health Survey (SF-36) questionnaire for 544 patients evaluated between 1994 and 2002. At baseline, the scores were significantly lower on all 8 SF-36 scales compared with age-matched population norms: the composite physical component summary (PCS) for the AL patients was 34.5 versus the population norm of 46.8, and the mental component summary (MCS) was 45.0 versus the norm of 51.5. All SF-36 scores improved at 1 year, with the MCS reaching the population norm. The PCS, though improved, was still lower than normal but was greater in the subgroup of patients who achieved a hematologic CR; the PCS normalized at 2 years in these patients. Thus, treatment of AL amyloidosis patients with HDM/SCT produces measurable and sustained improvements in quality of life, particularly in those patients who achieve hematologic CR.

Amyloidosis↗
PubMed2004

High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study.

BACKGROUND: AL amyloidosis is a fatal disease resulting from tissue deposition of amyloid fibrils derived from monoclonal immunoglobulin light chains. Treatment with oral chemotherapy is minimally effective. OBJECTIVE: To test survival and organ response in a large sample of patients treated with high-dose intravenous melphalan (100 to 200 mg/m2) and autologous blood stem-cell transplantation. DESIGN: 8-year longitudinal analysis of clinical effectiveness. SETTING: University-affiliated specialty referral clinic. PATIENTS: 701 consecutive new patients with AL amyloidosis. INTERVENTION: High-dose chemotherapy and autologous stem-cell transplantation for patients who met eligibility requirements based on organ involvement and clinical status. MEASUREMENTS: Survival analysis of all patients evaluated and a detailed analysis of treatment outcome in the subgroup that received high-dose melphalan and stem-cell transplantation. RESULTS: Among 701 patients with AL amyloidosis, 394 (56%) were eligible for high-dose melphalan and stem-cell transplantation; 82 did not proceed with treatment because of patient choice or disease progression. Median survival of the 312 patients who initiated treatment was 4.6 years. A complete hematologic response, defined as no evidence of an underlying plasma cell dyscrasia 1 year after treatment, was achieved in 40% of patients and was associated with prolonged survival. Statistically significant improvements occurred in end-organ disease and were greater in patients with a complete hematologic response. Mortality rate within 100 days of treatment with high-dose melphalan and stem-cell transplantation was 13%; patients with cardiomyopathy had the highest mortality rates. CONCLUSIONS: Treatment of selected patients with AL amyloidosis by using high-dose melphalan and stem-cell transplantation resulted in hematologic remission, improved 5-year survival, and reversal of amyloid-related disease in a substantial proportion.

Aged↗
PubMed2004

Longitudinal myocardial velocity gradient derived from pulsed Doppler tissue imaging in AL amyloidosis: a sensitive indicator of systolic and diastolic dysfunction.

OBJECTIVE: This study was performed to clarify whether the longitudinal myocardial velocity gradient could give new insights into the features of congestive heart failure in patients with primary amyloidosis. METHODS: A total of 33 consecutive patients with biopsy specimen-proven primary amyloidosis were examined by pulsed Doppler tissue imaging. RESULTS: In all, 22 had evidence of heart involvement, of whom 11 had clinical congestive heart failure. Sample volumes were placed on basal and midventricle in the apical 2- and 4-chamber views. Peak systolic, and peak early and late diastolic wall-motion velocities were measured at each site. Longitudinal myocardial velocity gradients were calculated as the difference between basal and midmyocardial velocities. Single-point analysis of pulsed Doppler tissue imaging could not distinguish any difference among groups, whereas the longitudinal myocardial velocity gradients in systole and early diastole were significantly impaired in the patients with congestive heart failure compared with both the patients without cardiac involvement and those with cardiac amyloidosis without congestive heart failure. CONCLUSION: Longitudinal myocardial velocity gradient is a sensitive method for detecting systolic and diastolic dysfunction in cardiac amyloidosis and is superior to single-point analysis Doppler tissue imaging.

Adult↗
PubMed2004

The increasing need for anticoagulant therapy to prevent stroke in patients with atrial fibrillation.

Ischemic stroke, a major complication of atrial fibrillation (AF), is believed to result from atrial thrombus formation caused by ineffective atrial contraction. Oral anticoagulant therapy effectively reduces the risk of ischemic stroke in patients with AF; this therapy is recommended for patients with any frequency or duration of AF and other risk factors for stroke, such as increased age (>75 years), hypertension, prior stroke, left ventricular dysfunction, diabetes, or heart failure. Recently published data comparing rate-control and rhythm-control strategies in AF emphasized the importance of maintaining an international normalized ratio higher than 2.0 during warfarin therapy and the need for continuing anticoagulant therapy to prevent stroke in high-risk patients, even if the strategy is rhythm control. Hemorrhagic complications can be minimized by stringent control of the international normalized ratio (particularly in elderly patients) and appropriate therapy for comorbidities such as hypertension, gastric ulcer, and early-stage cancers. Undertreatment of patients with AF is a continuing problem, particularly in the elderly population. Patients perceived as likely to be noncompliant, such as the functionally impaired, are less likely to receive warfarin therapy. However, stroke prevention with anticoagulants is cost-effective and improves quality of life, despite the challenges of maintaining appropriate anticoagulation with monitoring and warfarin dose titration. New medications in development with more predictable dosing and fewer drug-drug interactions may reduce the complexities of achieving optimal anticoagulation and increase the practicality of long-term anticoagulant therapy for patients with AF at risk of stroke.

Aged↗
PubMed2003

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]).

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

Aged↗
PubMed2003

Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis.

BACKGROUND: AL amyloidosis with heart failure is associated with decreased longitudinal myocardial contraction measured by pulsed tissue Doppler imaging. We sought to clarify whether new modalities of myocardial strain Doppler (change in length per unit length) or strain rate (the temporal derivative of strain) were more sensitive than tissue Doppler and could detect early regional myocardial dysfunction before the onset of congestive heart failure (CHF) in patients with AL (primary) amyloidosis. METHODS AND RESULTS: Ninety-seven biopsy-proven patients with AL amyloidosis were divided into 3 groups. Group 1 patients had no cardiac involvement (n=36), group 2 had heart involvement but no CHF (n=32), and group 3 had heart involvement and CHF (n=29). All patients underwent tissue velocity (TV) imaging, strain, and strain rate imaging (SR) at the basal, mid, and apical ventricle in 2 apical views. With the use of TV, differences in systolic function were only apparent between group 3 (basal mean value, 3.0+/-1.1 cm/s) and groups 1 and 2 (5.0+/-1.3 and 4.6+/-1.2 cm/s, respectively). In contrast, basal peak systolic SR (l/s) showed significant differences among all 3 groups (-2.0+/-0.4, -1.55+/-0.6, and -0.76+/-0.3 for groups 1 to 3, respectively. P<0.01). Basal strain also demonstrated statistically significant differences among the groups (-19+/-4%, -15+/-4.5%, and -8.0+/-5%; P<0.01). CONCLUSIONS: Cardiac amyloidosis is characterized by an early impairment in systolic function at a time when fractional shortening remains normal. This abnormality precedes the onset of CHF and can be detected by strain and SR but is not apparent by TV imaging.

Amyloidosis↗
PubMed2003

Persistent pleural effusions in primary systemic amyloidosis: etiology and prognosis.

BACKGROUND: Restrictive cardiomyopathy frequently complicates primary systemic amyloidosis (AL), yet only a small number of these patients develop large pleural effusions refractory to diuretic therapy and thoracentesis. We hypothesized that disruption of pleural function by amyloid deposits underlies persistent pleural effusions (PPEs) in patients with AL disease. METHODS: We performed a retrospective study of AL patients with and without PPEs who had been referred to Boston University between 1994 and 2001. The presence of PPEs was defined by a failure to resolve the condition with thoracentesis and aggressive diuresis. AL cardiomyopathy patients without pleural effusions constituted the control (cardiac) group. Indexes of plasma cell dyscrasia, nephrotic syndrome, thyroid function, and echocardiographic measures of left and right ventricle performance were compared between groups. When available, closed needle biopsies and autopsy specimens of parietal pleura were examined for amyloid deposits. RESULTS: Among 636 patients with AL, 35 PPE patients underwent a median of three thoracenteses each. No statistical differences were found between the PPE and cardiac groups in echocardiographic measures of septal thickness, left ventricular systolic function, or diastolic compliance. Right ventricular (RV) hypokinesis occurred more often in PPE patients; however, nearly half of this group had normal RV systolic function. Renal function, plasma protein levels, and thyroid function were the same between groups. Nephrotic range proteinuria (ie, > 3 g/d) was more prevalent in the cardiac group than in the PPE group (44% vs 26%, respectively; p = 0.057). All pleural biopsies in the PPE group (six biopsies) revealed amyloid deposits. Autopsy samples of parietal pleura were negative for disease in two cardiac patients. Eighteen patients had chest tubes placed, and 11 underwent pleurodesis. PPE signaled limited survival among patients who were ineligible for treatment. Untreated PPE patients lived a median 1.8 months vs 6 months for untreated cardiac patients (p = 0.031). Survival after intensive chemotherapy and autologous stem cell transplantation was comparable in the PPE and cardiac groups (21.8 vs 15.6 months, respectively; p = 0.405). CONCLUSION: In AL patients with cardiac amyloid, neither echocardiographic measures of ventricular function nor the degree of nephrosis distinguished those patients with PPEs. We conclude that pleural amyloid infiltration plays a central role in the creation and persistence of pleural effusions among patients with AL.

Aged↗