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Biomedical subjects

Daniel Burkhoff

Publications and source records attributed to Daniel Burkhoff.

At least 55 records · Page 3Linked to original sources
PubMed2004

Chronic electrical stimulation during the absolute refractory period of the myocardium improves severe heart failure.

AIM: In experimental studies, nonexcitatory electrical stimulation delivered at the time of absolute myocardial refractoriness resulted in cardiac contractility modulation (CCM) with improved systolic function. This study reports the initial experience with CCM in patients with chronic heart failure. METHODS AND RESULTS: Twenty-five patients, 23 males, with a mean age of 62+/-9 years and drug-refractory NYHA class III heart failure were assigned to CCM-generator implantation. The underlying heart disease was idiopathic dilated cardiomyopathy in 12 patients and coronary heart disease in 13 patients. Acute efficacy of CCM with 7.73-V stimuli delivered via two right ventricular leads was evaluated by measuring the time derivative of left ventricular pressure (dP/dt). After implantation, the CCM generator was activated for 3 h daily over 8 weeks. In 23/25 patients the CCM system was implanted successfully. Heart failure significantly improved from NYHA class III to class II in 15 patients and to class I in 4 patients (p < 0.000001), left ventricular ejection fraction improved from 22+/-7% to 28+/-8% (p = 0.0002), and the Minnesota Living with Heart Failure Score improved from 43+/-22 to 25+/-18 (p = 0.001). The 6-min walk test increased from 411+/-86 to 465+/-81 m (p= 0.02). Nine patients (39%) had intermittent sensations associated with CCM delivery. There were two (8%) non-device-related deaths during follow-up. CONCLUSIONS: These preliminary data indicate that CCM by delivery of intermittent nonexcitatory electrical stimuli is a promising technique for improving ventricular systolic function and symptoms in patients with drug-refractory NYHA class III heart failure.

Cardiomyopathy, Dilated↗
PubMed2004

Temporary assist device for postcardiotomy cardiac failure.

Postcardiotomy left ventricular failure (LVF) complicating a cardiac surgical procedure is usually managed with intraaortic balloon pump (IABP) counterpulsation. We report two cases of postcardiotomy LVF unresponsive to inotropic support and IABP counterpulsation that were managed successfully with the use of the TandemHeart percutaneous ventricular assist device (pVAD) (CardiacAssist, Pittsburgh, PA). The TandemHeart pVAD appears to be safe and effective as a bridge to recovery in the treatment of postcardiotomy cardiac failure.

Aged↗
PubMed2004

Macrophage inhibitor, semapimod, reduces tumor necrosis factor-alpha in myocardium in a rat model of ischemic heart failure.

Pharmaceutical agents aimed at reducing tumor necrosis factor-alpha (TNF-alpha) levels appeared to be attractive possibilities in the medical management of heart failure, as heart failure was shown to be associated with high TNF-alpha levels. However, therapies specifically targeting TNF-alpha failed to show any survival benefit. We examined whether a broad inhibition of inflammatory cytokine production secondary to macrophage inhibition would be more effective at improving cardiac function in the setting of heart failure. To this end, we studied Semapimod (formerly known as CNI-1493), a synthetic guanylhydrazone that inhibits macrophage activation and the production of several inflammatory cytokines. Left anterior descending coronary ligation surgery was performed on each animal to induce a myocardial infarction. After confirming heart failure by echocardiography, the animals were randomly assigned to one of four groups: (1) rats with myocardial infarct receiving high-dose Semapimod, 10 mg/kg/d (MI-H, N = 13); (2) rats with myocardial infarct receiving low-dose Semapimod, 3 mg/kg/d (MI-L, N = 9); (3) rats with myocardial infarct receiving vehicle treatment, 2.5% mannitol in water (MI-0, N = 9); and (4) control rats with sham operation and vehicle treatment (Sham, N = 10). Both Semapimod and vehicle treatments were administered by daily tail vein injections over a course of five days. Echoes were repeated at 2, 5, and 9 weeks following treatment. At 9 weeks, hemodynamic data were collected and the animals were euthanized. Trichrome staining was done to assess infarct, and immunohistochemistry was performed to assess TNF-alpha levels. Prior to drug administration, serum was taken from 5 random rats. No detectable level of TNF-alpha was seen (lower limit of detection for the assay used = 12.5 pg/mL). Also prior to any treatment, echocardiography confirmed significant cardiac impairment of rats undergoing LAD ligation as compared with sham. Over the course of the 9 weeks, there were 4 deaths, all in the MI-H group. There was no difference between Semapimod-treated animals and vehicle-treated MI animals in any echocardiographic or hemodynamic parameter. TNF-alpha staining in the noninfarcted region was evident only in the MI groups, not the sham group. When blindly compared on a semiquantitative scale (ie, 0 = no visible staining to 3 = marked staining), a significant difference in staining was observed between MI-0 versus MI-H (1.19 +/- 0.32 versus 0.33 +/- 0.14; P = 0.03) and between MI-0 and MI-L (1.19 +/- 0.32 versus 0.39 +/- 0.22; P = 0.05). In this setting, despite the fact that Semapimod treatment decreased tissue TNF-alpha levels, it did not improve cardiac function, and at high doses it was associated with higher mortality. These results in a rodent model confirm the results of clinical trials with etanercept and infliximab (ie, that decreasing TNF levels in plasma or tissues does not improve cardiac function and may actually increase mortality).

Animals↗
PubMed2004

Outcomes following percutaneous coronary intervention in patients previously considered "without option": a subgroup analysis of the PACIFIC Trial.

OBJECTIVES: The present study assesses clinical outcomes in patients from the Potential Angina Class Improvement From Intramyocardial Channels (PACIFIC) trial of percutaneous transmyocardial revascularization (PTMR) who had previously been considered "no-option," but who subsequently underwent percutaneous coronary intervention (PCI) for continuing symptoms. BACKGROUND: Patients with advanced symptomatic coronary artery disease who are not candidates for coronary artery bypass grafting (CABG) or PCI comprise an important group, for which no established treatment is currently available. These patients have been described as having "no option," and are currently targeted for various experimental therapies. One such proposed therapy, PTMR, was recently examined in the PACIFIC trial. A subgroup of patients in this trial subsequently underwent PCI, although to initially qualify for the study they had previously been considered as unsuitable for PCI and as having "no option." The therapeutic benefit of PCI for patients of this type is unknown. METHODS: A retrospective analysis was performed on data obtained from all subjects of the PACIFIC study who underwent PCI within the 12-month follow-up period. RESULTS: Ten subjects originally randomized to PTMR and 11 subjects from the medical treatment group underwent PCI. Most had undergone at least one prior PCI and at least one CABG, and there was a high prevalence of cardiovascular risk factors. Despite excellent immediate procedural success, PCI resulted in only modest, statistically nonsignificant increases in mean exercise duration, small improvements in angina status, and no significant improvements in quality of life. CONCLUSIONS: These data suggest that PCI provides only marginal-if any-symptomatic benefit in these patients.

Adult↗
PubMed2003

Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure.

BACKGROUND: Chronic beta-adrenergic receptor (beta-AR) blockade improves cardiac contractility and prolongs survival in patients with heart failure; however, the mechanisms underlying these favorable responses are poorly understood. Stress-induced activation of the sympathetic nervous system results in protein kinase A (PKA)-mediated phosphorylation of the calcium (Ca2+) release channel/cardiac ryanodine receptor (RyR2), required for cardiac excitation-contraction (EC) coupling, activating the RyR2 channel, and increasing cardiac contractility. The hyperadrenergic state of heart failure results in leaky RyR2 channels attributable to PKA hyperphosphorylation and depletion of the stabilizing FK506 binding protein, FKBP12.6. We tested the hypothesis that improved cardiac muscle function attributable to beta-AR blockade is associated with restoration of normal RyR2 channel function in patients with heart failure. METHODS AND RESULTS: We assessed the effects of beta-AR blockade on left ventricular volume using isolated perfused hearts and beta-agonist responsiveness using muscle strips from patients undergoing transplantation. Twenty-four human hearts were examined, 10 from patients with heart failure treated with beta-AR blockers (carvedilol, metoprolol, or atenolol), 9 from patients with heart failure without beta-AR blocker treatment, and 5 normal hearts. RyR2 PKA phosphorylation was determined by back-phosphorylation, FKBP12.6 in the RyR2 macromolecular complex was determined by coimmunoprecipitation, and channel function was assayed using planar lipid bilayers. beta-AR blockers reduced left ventricular volume (reverse remodeling) and restored beta-agonist response in cardiac muscle from patients with heart failure. Improved cardiac muscle function was associated with restoration of normal FKBP12.6 levels in the RyR2 macromolecular complex and RyR2 channel function. CONCLUSIONS: Improved cardiac muscle function during beta-AR blockade is associated with improved cardiac Ca2+ release channel function in patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed2003

Use of rapamycin slows progression of cardiac transplantation vasculopathy.

BACKGROUND: Cardiac transplantation vasculopathy is the leading cause of late death in heart transplantation recipients. Rapamycin is an immunosuppressant drug with potent antiproliferative and antimigratory effects. We investigated whether rapamycin could prevent progression of graft vasculopathy in 46 patients (age, 54+/-10 years; 4.3+/-2.3 years after transplantation) with severe disease. METHODS AND RESULTS: At annual cardiac catheterization, patients were randomly assigned to treatment with rapamycin (n=22) versus continued current immunosuppression (n=24). Clinical characteristics including recipient age and sex, underlying cause of congestive heart failure, donor age and sex, and ischemic time were recorded. Cardiac catheterization was graded with the use of a semiquantitative scale and repeated annually. Clinically significant adverse events were defined as death, need for angioplasty or bypass surgery, myocardial infarction, and a >25% worsening of the catheterization score. These events were monitored as primary study end points. Anti-HLA class I and II antibody production and lymphocyte growth assays were measured with each biopsy. Patients selected for rapamycin had azathioprine or mycophenolate mofetil discontinued and were given rapamycin. Outcomes were compared by means of log-rank analysis. There were no significant differences in baseline characteristics. Duration of follow-up was comparable (rapamycin, 689+/-261; control, 630+/-207 days; NS). In the rapamycin group, 3 patients reached primary end points versus 14 patients in the control group (P<0.001). There was no difference in baseline or subsequent anti-HLA class I or II antibody production. CONCLUSIONS: In this patient cohort with cardiac vasculopathy, treatment with rapamycin slowed disease progression probably by its antiproliferative and antimigratory effects.

Arterial Occlusive Diseases↗
PubMed2003

PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure.

The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is the major calcium (Ca2+) release channel required for skeletal muscle excitation-contraction (EC) coupling. RyR1 function is modulated by proteins that bind to its large cytoplasmic scaffold domain, including the FK506 binding protein (FKBP12) and PKA. PKA is activated during sympathetic nervous system (SNS) stimulation. We show that PKA phosphorylation of RyR1 at Ser2843 activates the channel by releasing FKBP12. When FKB12 is bound to RyR1, it inhibits the channel by stabilizing its closed state. RyR1 in skeletal muscle from animals with heart failure (HF), a chronic hyperadrenergic state, were PKA hyperphosphorylated, depleted of FKBP12, and exhibited increased activity, suggesting that the channels are "leaky." RyR1 PKA hyperphosphorylation correlated with impaired SR Ca2+ release and early fatigue in HF skeletal muscle. These findings identify a novel mechanism that regulates RyR1 function via PKA phosphorylation in response to SNS stimulation. PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF.

Animals↗
PubMed2002

Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

We assessed the feasibility of cardiac contractility modulation (CCM) by electric currents applied during the refractory period in patients with heart failure (HF). Extracellular electric currents modulating action potential and calcium transients have been shown to potentiate myocardial contractility in vitro and in animal models of chronic HF. CCM signals were biphasic square-wave pulses with adjustable amplitude, duration, and time delay from sensing of local electric activity. Signals were applied to the left ventricle through an epicardial vein (in 12 patients) or to the right ventricular (RV) aspect of the septum endocardially (in 6 patients). Simultaneous left ventricular (LV) and aortic pressure measurements were performed using a Millar catheter (Millar Instruments, Houston, Texas). Hemodynamics during RV temporary dual-chamber pacing was regarded as the control condition. Both LV and RV CCM stimulation increased dP/dt(max) to a similar degree (9.1 +/- 4.5% and 7.1 +/- 0.8%, respectively; p <0.01 vs controls), with associated aortic pulse pressure changes of 10.3 +/- 7.2% and 10.8 +/- 1.1% (p <0.01 vs controls). Regional systolic wall motion assessed quantitatively by color kinesis echocardiography was markedly enhanced near the CCM electrode, and the area of increased contractility involved 4.6 +/- 1.2 segments per patient. In 6 patients with HF with left bundle branch block, CCM signals delivered during biventricular pacing (BVP) produced an additional 16.1 +/- 3.7% increase in dP/dt(max) and a 17.0 +/- 7.5% increase in pulse pressure compared with BVP alone (p <0.01). CCM stimulation in patients with HF enhanced regional and global measures of LV systolic function, regardless of the varied delivery chamber or whether modulation was performed during RV pacing or BVP.

Aorta↗
PubMed2002

Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart.

We investigated the mechanism of positive inotropism of electric currents applied during the absolute refractory period. Ten Langendorff-perfused ferret hearts were instrumented to measure isovolumic left ventricular pressure (LVP) and the aequorin luminescence. Biphasic square-wave electric currents (+/-20 mA, total duration 30 ms) were delivered between pairs of electrodes. Six hearts were perfused at different extracellular Ca(2+) concentrations ([Ca(2+)](o); 1, 2, 4, and 8 mM). These signals increased LVP from 50.0 +/- 9.4 to 70.1 +/- 14.7, from 67.5 +/- 11.0 to 79.0 +/- 15.6, from 79.3 +/- 21.0 to 87.1 +/- 22.8, and from 84.6 +/- 24.0 to 91.8 +/- 28.5 mmHg at the respective [Ca(2+)](o) (P < 0.05). Peak free intracellular [Ca(2+)] ([Ca(2+)](i)) increased from 0.52 +/- 0.13 to 1.37 +/- 0.23, from 0.76 +/- 0.23 to 1.73 +/- 0.14, from 1.10 +/- 0.24 to 2.05 +/- 0.33, and from 1.41 +/- 0.36 to 2.24 +/- 0.36 microM/ml, respectively (P < 0.001). With the use of 1 mg/l propranolol with 1 mM [Ca(2+)](o), LVP and [Ca(2+)](i) were increased significantly from 48.7 +/- 8.18 to 56.3 +/- 6.11 mmHg and from 0.61 +/- 0.11 to 1.17 +/- 0.20 microM, respectively (P < 0.05). In conclusion, positive inotropism of such electrical currents was due to increased peak [Ca(2+)](i) and Ca(2+) responsiveness of the myofilaments did not change significantly.

Adrenergic beta-Antagonists↗
PubMed2002

Protein kinase A phosphorylation of the cardiac calcium release channel (ryanodine receptor) in normal and failing hearts. Role of phosphatases and response to isoproterenol.

The cardiac ryanodine receptor/calcium release channel (RyR2) on the sarcoplasmic reticulum (SR) comprises a macromolecular complex that includes a kinase and two phosphatases that are bound to the channel via targeting proteins. We previously found that the RyR2 is protein kinase A (PKA)-hyperphosphorylated in end-stage human heart failure. Because heart failure is a progressive disease that often evolves from hypertrophy, we analyzed the RyR2 macromolecular complex in several animal models of cardiomyopathy that lead to heart failure, including hypertrophy, and at different stages of disease progression. We now show that RyR2 is PKA-hyperphosphorylated in diverse models of heart failure and that the degree of RyR2 PKA phosphorylation correlates with the degree of cardiac dysfunction. Interestingly, we show that RyR2 PKA hyperphosphorylation can be lost during perfusion of isolated hearts due to the activity of the endogenous phosphatases in the RyR2 macromolecular complex. Moreover, infusion of isoproterenol resulted in PKA phosphorylation of RyR2 in rat, indicating that systemic catecholamines can activate phosphorylation of RyR2 in vivo. These studies extend our previous analyses of the RyR2 macromolecular complex, show that both the kinase and phosphatase activities in the macromolecular complex are regulated physiologically in vivo, and suggest that RyR2 PKA hyperphosphorylation is likely a general feature of heart failure.

Animals↗
PubMed2002

Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device.

BACKGROUND: Failing hearts can exhibit elements of structural and molecular "reverse remodeling" after support with a left ventricular assist device (LVAD). The present study examined LVAD-induced remodeling of cardiac mitochondria. METHODS: Left ventricular tissue from 20 failing and 21 LVAD-supported hearts, catagorized as ischemic (ICM) or dilated (DCM) cardiomyopathy and four nonfailing hearts were studied. Myocyte mitochondrial ultrastructure was assessed by high-performance liquid chromatography determination of cardiolipin, a specific lipid component of the inner membrane, and its three major molecular species: L4, L3O, and L2O2. RESULTS: Both failing and LVAD-supported hearts exhibited a reduction in cardiolipin content that was independent of the type of cardiomyopathy. However, in failing/ICM hearts, there was a 25% increase in the L4/L3O ratio and a 70% increase in the L4/L2O2 ratio, indicating a change in cardiolipin composition. These alterations were normalized by LVAD support. In sharp contrast, molecular species ratios in DCM hearts were the same as those in nonfailing hearts regardless of whether LVAD support had been used or not. CONCLUSIONS: These data demonstrate LVAD-induced reverse remodeling of myocyte cardiolipin composition in ICM but not DCM hearts.

Adult↗
PubMed2002

Direct cardiac compression devices.

Ventricular assist devices employed clinically to assist the failing heart require direct contact between the device and the patient's blood. Thromboembolic events, the need for anticoagulation, hemolysis, immune reactions and infections contribute significantly to morbidity and mortality of these devices. Compressing the weakened heart from its epicardial surface, direct cardiac compression (DCC), could provide ventricular support and avoid the interactions between blood and a foreign surface. This article reviews the physiology of epicardial compression and the current progress of mechanical compression devices.

Animals↗
PubMed2002

Alternatives to traditional coronary bypass surgery.

Over 1 million percutaneous coronary interventions (PCI) and a half million surgical coronary artery bypass grafting procedures (CABG) are performed in the United States annually for treatment of coronary artery disease. With recent advances in anti-restenosis strategies, the number of PCIs is expected to increase dramatically. Still, these therapies treat relatively discrete coronary lesions. However, there is a relatively large number of patients for whom traditional therapies are not optimal, either because there are diffuse coronary artery lesions, because there are chronic total occlusions, or because, in the instance of bypass surgery, creating proximal or distal anastomoses is problematic. We review three strategies in various stages of development aimed at treating patients not optimally served by traditional forms of revascularization: transmyocardial laser revascularization, angiogenic therapies, and direct ventricle-to-coronary artery bypass.

Animals↗
PubMed2002

Do transmyocardial and percutaneous laser revascularization induce silent ischemia? An assessment by exercise testing.

BACKGROUND: Transmyocardial and percutaneous laser revascularization (TMR, PTMR) may reduce angina and increase exercise tolerance in otherwise untreatable angina patients, although the mechanism is unknown and the placebo effect may be significant. One other proposed mechanism is cardiac denervation leading to silent ischemia. METHODS: Electrocardiograms obtained during symptom-limited exercise (ETT, modified Bruce protocol) at baseline and 12 months were analyzed (blinded core laboratory) from 182 patients randomized to TMR (n = 92) or medical therapy alone (MED(TMR), n = 90) and 219 patients randomized to PTMR (n = 109) or medical therapy alone (MED(PTMR), n = 110). RESULTS: Exercise duration increased 1 year after TMR or PTMR relative to medically treated patients (6.8 +/- 3.4 min vs 8.6 +/- 3.5 min for TMR; 7.3 +/- 3.1 min vs 9.1 +/- 3.6 min for PTMR, P <.05). At baseline, 20% of TMR and MED(TMR) subjects had ST depression >1.0 mm, >80% had angina during exercise, but only 3% had ST changes without chest pain (silent ischemia). This did not change after TMR. In the PTMR group, more subjects exercised to >1.0 mm ST depression (from 17% to 34%, P <.05), with no change in MED(PTMR), but the proportion with silent ischemia did not change in either group. CONCLUSION: Exercise tolerance improved after TMR and after PTMR. Relative to PTMR, TMR more effectively suppressed pain during exercise and ischemic ST depression. However, neither TMR nor PTMR induced significant silent ischemia. These results suggest that denervation may not be a significant factor contributing to angina relief after these procedures. The contribution of the placebo effect was not determined by these results.

Adult↗
PubMed2002

Load dependence of ventricular performance explained by model of calcium-myofilament interactions.

Although a simple concept of load-independent behavior of the intact heart evolved from early studies of isolated, intact blood-perfused hearts, more recent studies showed that, as in isolated muscle, the mode of contraction (isovolumic vs. ejection) impacts on end-systolic elastance. The purpose of the present study was to test whether a four-state model of myofilament interactions with length-dependent rate constants could explain the complex contractile behavior of the intact, ejecting heart. Studies were performed in isolated, blood-perfused canine hearts with intracellular calcium transients measured by macroinjected aequorin. Measured calcium transients were used as the driving function for the model, and length-dependent rate constants yielding the highest concordance between measured and model-predicted midwall stress at different isovolumic volumes were determined. These length-dependent rate constants successfully predicted contractile behavior on ejecting contractions. This, along with additional model analysis, suggests that length-dependent changes in calcium binding affinity may not be an important factor contributing to load-dependent contractile performance in the intact heart under physiological conditions.

Actin Cytoskeleton↗
PubMed2002

Cardiac contractility modulation by electric currents applied during the refractory period.

Inotropic effects of electric currents applied during the refractory period have been reported in cardiac muscle in vitro using voltage-clamp techniques. We investigated how electric currents modulate cardiac contractility in normal canine hearts in vivo. Six dogs were instrumented to measure regional segment length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac contractility modulating (CCM) electric currents (biphasic square pulses, amplitude +/-20 mA, total duration 30 ms) were delivered during the refractory period between pairs of electrodes placed on anterior and posterior walls. CCM significantly increased index of global contractility (E(es)) from 5.9 +/- 2.9 to 8.3 +/- 4.6 mmHg/ml with anterior CCM, from 5.3 +/- 1.8 to 8.9 +/- 4.0 mmHg/ml with posterior CCM, and from 6.1 +/- 2.6 to 11.0 +/- 7.0 mmHg/ml with combined CCM (P < 0.01, no significant change in volume axis intercept). End-systolic pressure-segment length relations showed contractility enhancement near CCM delivery sites, but not remotely. Relaxation was not influenced. CCM increased mean aortic pressure, but did not change peripheral resistance. Locally applied electrical currents enhanced global cardiac contractility via regional changes in myocardial contractility without impairing relaxation in situ.

Animals↗
PubMed2002

Transmyocardial laser revascularization: a review of basic and clinical aspects.

Transmyocardial laser revascularization (TMR or TMLR) is a surgical therapy developed to treat patients with debilitating, medically refractory angina pectoris due to epicardial coronary artery disease that is not amenable to treatment using the traditional methods of percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). This technique can also be applied percutaneously [percutaneous myocardial revascularization (PMR) or direct myocardial revascularization (DMR)]. The original hypotheses which motivated development of TMR were that: (i) oxygenated blood could flow directly from the left ventricle and perfuse the myocardium; and (ii) such artificially created channels would remain patent. However, experimental data have refuted both hypotheses. In the face of early reports of marked clinical benefits in terms of relief of anginal symptoms, alternate hypotheses to explain the mechanism have been pursued, including TMR-associated neoangiogenesis and cardiac denervation. Clinically, numerous reports of reduction in frequency and severity of anginal symptoms, improved exercise tolerance and improved quality of life have appeared from nonblind registry-type studies as well as nonblind randomized clinical trials of TMR or PMR versus continued medical therapy. TMR was not associated with a significant improvement in survival compared with medical therapy alone in randomized trials. For example, the prospective, randomized Angina Treatments-Lasers and Normal Therapies in Comparison (ATLANTIC) trial found a 1-year mortality of 5% in 92 TMR-treated patients and 10% in 90 patients treated with medication only. No proof of improved myocardial blood flow in hearts of treated patients is currently available. The first randomized study of PMR was the Potential Angina Class Improvement From Intramyocardial Channels (PACIFIC) trial which found significantly greater improvements in anginal symptoms and exercise tolerance with PMR plus medical therapy, compared with medical therapy alone. The preliminary results of two double-blind studies with PMR/DMR have been presented but have not yet been published in full. Whereas PMR-treated patients did significantly better than sham-treated control groups after 6 months in the Blinded Evaluation of Laser Intervention Electively For angina pectoris (BELIEF) trial, there was no difference after 1 year between DMR-treated patients and those treated with medication only in the DMR In Regeneration of Endomyocardial Channels Trial (DIRECT). Different devices used for revascularization in these two trials may explain the disparity in the results, and therefore the efficacy and tolerability of each device should be judged upon data collected with that particular device.

Angina Pectoris↗