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Rodney H Falk

Publications and source records attributed to Rodney H Falk.

13 recordsLinked to original sources
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↗
PubMed2003

Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis.

Thalidomide is an effective therapy for multiple myeloma, although its mechanisms of action remain unclear. Light chain-associated (AL) amyloidosis is a plasma cell disorder related to multiple myeloma, but in AL amyloidosis, fibrillar tissue deposits of clonal immunoglobulin light chains produce organ dysfunction. To test the toxicity and efficacy of thalidomide in AL amyloidosis we initiated a phase I/II trial for patients with AL amyloidosis, most of whom had failed prior therapy with high-dose melphalan and autologous stem cell transplantation. This trial was designed as an individualized 6-month dose-escalation study with reevaluation of bone marrow plasmacytosis and serum and urine monoclonal proteins after 3 and 6 months. Sixteen patients were enrolled in the study with a median age of 62 years (range, 37-70 years). Fourteen patients had renal involvement, 4 had cardiac involvement, 4 had liver involvement, and 2 had predominant soft tissue or lymph node involvement. The median maximum tolerated dose was 300 mg, with fatigue and other central nervous system side effects being the major dose-limiting toxicities. Side effects not frequently reported for other patient populations included exacerbation of peripheral and pulmonary edema and worsening azotemia. In all, 50% of patients experienced grade 3/4 toxicity, and 25% had to discontinue the study drug. No complete hematologic responses were seen, but 25% of patients had a significant reduction in Bence-Jones proteinuria. Thus, while thalidomide has activity in AL amyloidosis, it also has significant toxicity in this patient population.

Adult↗
PubMed2002

Prognostic significance of ultrasound myocardial tissue characterization in patients with cardiac amyloidosis.

BACKGROUND: Cycle-dependent variation of myocardial integrated backscatter (CV-IB) is an objective measurement that may detect myocardial abnormalities. However, no data exist about the prognostic value of CV-IB in primary cardiac amyloidosis. METHODS AND RESULTS: We prospectively examined 208 consecutive biopsy-proven patients with primary amyloidosis. The magnitude of CV-IB was analyzed at the interventricular septum and left ventricular (LV) posterior wall and its prognostic value was compared with standard Doppler measurements with to the Tei index (isovolumic contraction time plus isovolumic relaxation time divided by ejection time). One hundred thirty-three patients had cardiac involvement (mean LV thickness > 12 mm). Forty-one patients (20%) (32 cardiac deaths) died during a mean follow-up of period of 307+/-156 days. Univariate analysis showed that the CV-IB at the LV posterior wall was the best predictor of cardiac death (P<0.0001) and all-cause death (P< 0.0001). The Tei index did not identify patients at risk of death. Multivariate analysis showed that CV-IB at the LV posterior wall was the only independent predictor of both cardiac and overall deaths. CONCLUSIONS: Among patients with cardiac amyloidosis, CV-IB at the LV posterior wall is a powerful predictor of clinical outcome and is superior to standard echocardiographic/Doppler flow indexes.

Amyloidosis↗
PubMed2002

Usefulness of pulsed tissue Doppler imaging for evaluating systolic and diastolic left ventricular function in patients with AL (primary) amyloidosis.

To clarify whether pulsed tissue Doppler imaging at multiple left ventricular LV sites could help to explain the mechanism of congestive heart failure (CHF) in patients with primary amyloidosis, we examined 86 consecutive patients with primary amyloidosis confirmed by biopsy (group I, 31 patients without cardiac involvement; group II, 31 patients with evidence of heart involvement but no CHF; and group III, 24 patients with heart involvement, clinical CHF, and normal fractional shortening >28%). Peak early diastolic myocardial velocities in group II were significantly lower than those in group I, and the values in group III were also significantly lower than those in group II at most sites. In contrast to diastolic abnormalities, peak systolic wall motion velocities in group III were significantly lower than those in group II, but there were no significant differences between groups I and II. Thus, cardiac amyloidosis is characterized by an initial impairment in early cardiac relaxation, whereas CHF is associated with an impairment of peak systolic wall motion velocities, most prominently seen in the longitudinal axis. This systolic dysfunction can be detected by pulsed tissue Doppler imaging, even when ejection fraction is in the normal range.

Amyloidosis↗
PubMed2002

Low-dose continuous oral melphalan for the treatment of primary systemic (AL) amyloidosis.

Median survival of patients with AL amyloidosis with clinically significant cardiac involvement is 5 months when treated with cyclic melphalan and prednisone. We investigated a regimen of continuous oral melphalan as a single agent for patients with cardiac amyloidosis who were unable to tolerate prednisone or more aggressive chemotherapy. Thirty patients with amyloid cardiomyopathy were treated with continuous oral melphalan. Seven of 13 patients, evaluable after 3-4 months of treatment, achieved a partial haematological response and three achieved a complete haematological response; six patients have survived for > 1 year. This regimen appeared to be effective in inducing haematological responses in patients who received total doses of melphalan > 300 mg.

Aged↗
PubMed2002

Identification of a novel transthyretin Thr59Lys/Arg104His. A case of compound heterozygosity in a Chinese patient diagnosed with familial transthyretin amyloidosis.

Transthyretin (TTR) is a 127-amino acid residue protein synthesized mainly in the liver and in several minor sites, including the choroid plexus and the eye. In plasma, TTR circulates as a homotetramer and transports the hormone thyroxine and the retinol-binding protein-vitamin A complex. It is hypothesized that amino acid substitutions in TTR destabilize the tetramer by causing each subunit toform intermediates that may self-associate into amyloid fibrils. Deposition of wild type TTR, its variants and/or fragments as amyloid fibrils in tissues and organs is associated with familial transthyretin amyloidosis (ATTR). Reported herein is the characterization of a novel TTR Thr59Lys/Arg104His in a patient of Chinese ancestry, who was diagnosed with ATTR. The two variant proteins and the double gene mutations in this compound heterozygous case were detected and identified using a multifaceted approach consisting of isoelectric focusing, electrospray ionization mass spectrometry (MS), matrix-assisted laser desorption/ionization time-of-flight MS in combination with enzymatic digestion, and direct DNA sequence analysis. Previous studies have shown that the TTR Arg104His variant is non-pathologic. It appeared to provide a protective effect in another compound heterozygous case (TTR Val30Met/Arg104His). However, the TTR Arg104His variant when presented with the TTR Thr59Lys variant did not seem to have any protective role.

Amino Acid Substitution↗
PubMedDate not supplied

Ventricular rate control in the elderly: is digoxin enough?

The ventricular response in untreated patients with atrial fibrillation often exceeds 120 beats/min at rest. Digoxin can slow this rate, but its efficacy during exertion may be limited. Alternatives, or additions, to digoxin therapy include the beta blockers and diltiazem or verapamil. This review discusses the role of digoxin in relation to these other drugs, with particular reference to the elderly population.

Age Factors↗