Advances in percutaneous treatment for adult valvular heart disease.

Valvular heart disease occurs in 2-3% of the general population with an increase in prevalence with advancing age. The aetiology of valvular heart disease has evolved in recent decades with degenerative aortic and mitral valve disease supplanting rheumatic heart disease as a primary cause. The common valve lesions to be discussed in this article are aortic stenosis and mitral regurgitation. The traditional approach to calcific aortic stenosis when either symptoms or left ventricular impairment develops is surgical aortic valve replacement and it remains a treatment with excellent outcomes. In recent years there has been interest in less invasive approaches, including percutaneous and transapical aortic valve implantation. With refinements in technology these approaches are becoming a potential treatment option, primarily for high-risk patients who may otherwise be unsuitable for traditional open surgical treatment. Catheter-based approaches for mitral valve disease are also evolving. Mitral regurgitation may often be the result of mitral annular dilatation seen in patients with an enlarged left ventricle or left atrium. Percutaneous implantation of a constricting device in the coronary sinus, which lies in close proximity to the mitral annulus, results in a change to the geometry of the mitral valve and reduced regurgitation. Another technique in patients with degenerative mitral regurgitation is the endovascular edge-to-edge repair in which coaptation of the mitral valve leaflets can be improved with a percutaneously deployed clip. Small patient series indicate that these new techniques are promising. As such, advances in percutaneous interventional and surgical approaches have the potential to further improve outcomes for selected patients with valvular heart disease.

Results of the study to determine rotablator and transluminal angioplasty strategy (STRATAS).

Rotational atherectomy is used to debulk calcified or complex coronary stenoses. Whether aggressive burr sizing with minimal balloon dilation (<1 atm) to limit deep wall arterial injury improves results is unknown. Patients being considered for elective rotational atherectomy were randomized to either an "aggressive" strategy (n = 249) (maximum burr/artery >0.70 alone, or with adjunctive balloon inflation < or = 1 atm), or a "routine" strategy (n = 248) (maximum burr/artery < or =0.70 and routine balloon inflation > or =4 atm). Patient age was 62 +/- 11 years. Fifty-nine percent routine and 60% aggressive strategy patients had class III to IV angina. Fifteen percent routine and 16% aggressive strategy patients had a restenotic lesion treated; lesion length was 13.6 versus 13.7 mm. Reference vessel diameter was 2.64 mm. Maximum burr size (1.8 vs 2.1 mm), burr/artery ratio (0.71 vs 0.82), and number of burrs used (1.9 vs 2.7) were greater for the aggressive strategy, p <0.0001. Final minimum lumen diameter and residual stenosis were 1.97 mm and 26% for the routine strategy versus 1.95 mm and 27% for the aggressive strategy. Clinical success was 93.5% for the routine strategy and 93.9% for the aggressive strategy. Creatine kinase-myocardial band (CK-MB) was >5 times normal in 7% of the routine versus 11% of the aggressive group. CK-MB elevation was associated with a decrease in rpm of >5,000 from baseline for a cumulative time >5 seconds, p = 0.002. At 6 months, 22% of the routine patients versus 31% of the aggressive strategy patients had target lesion revascularization. Angiographic follow-up (77%) showed minimum lumen diameter to be 1.26 mm in the routine group versus 1.16 mm in the aggressive group, and the loss index 0.54 versus 0.62. Dichotomous restenosis was 52% for the routine strategy versus 58% for the aggressive strategy. Multivariable analysis indicated that left anterior descending location (odds ratio 1.67, p = 0.02) and operator-reported excessive speed decrease >5,000 rpm (odds ratio 1.74, p = 0.01) were significantly associated with restenosis. Thus, the aggressive rotational atherectomy strategy offers no advantage over more routine burr sizing plus routine angioplasty. Operator technique reflected by an rpm decrease of >5,000 from baseline is associated with CK-MB elevation and restenosis.

Reduction in myocardial infarct size by basic fibroblast growth factor following coronary occlusion in a canine model.

In a canine model of permanent coronary occlusion it has been shown that basic fibroblast growth factor (bFGF) reduced infarct size and this was associated with an increase in myocardial capillary density a week after infarction. In a preliminary work from our own laboratory using a model of occlusion followed by prolonged reperfusion we observed a similar reduction in infarct size without evidence of myocardial neovascularization. The aim of the present investigation was to evaluate the effects of bFGF on infarct size and blood flow to the infarct zone in an acute experiment in which myocardial neovascularization would be excluded as a mechanism by the short duration of the study. Seventeen mongrel dogs were anesthetized and the heart was exposed through a left thoracotomy. The left anterior descending (LAD) coronary artery was isolated and occluded for 3 h. Fifteen min after LAD occlusion dogs received bFGF 20 microg of bFGF (n=6) or placebo (n=11) by intracoronary injection infused over 5 min. We measured heart rate, aortic pressure, regional coronary blood flow (CBF), regional shortening fraction (SF) at 1, 30 and 180 min of occlusion, then the LAD was reperfused for 5 min then the dogs were euthanized and infarct size was measured. Regional CBF was similar between the two groups of dogs throughout all the study. The SF was similar between the two groups prior the onset of ischemia and at the beginning of the ischemic period. After 180 min of ischemia SF was 2.7+/-4.1% for bFGF and -3.1+/-4.7 for placebo (P=0.049), and during reperfusion SF was 3.4+/-4.6% for bFGF and 0.4+/-1.0% for placebo treated dogs (P=0.023). The infarct size, normalized for the area at risk was 14.2+/-5.2% in bFGF group vs 25.8+/-8.2% in placebo group (P=0.015). In summary we have demonstrated that bFGF significantly limits myocardial necrosis after acute coronary occlusion, and that this occurred without an increase in regional myocardial perfusion and within a period of time too brief for angiogenesis to have occurred. By exclusion, it appears that the salutary effect of bFGF is likely to be mediated by a cellular mechanism. The mechanism or mechanisms responsible for myocardial salvage by bFGF may have significant potential to be exploited in the clinical arena as the basis for therapies to protect the acutely ischemic myocardium.

Left atrial tumour mimicking pulmonary embolism.

Primary cardiac tumours have been described as great imitators. They are rare, and clinical presentations are diverse. Diagnosis is usually made by two-dimensional echocardiography. The present case report describes a case where a left atrial fibrosarcoma eluded diagnosis by echocardiography, and was eventually demonstrated by computed tomography. Management was complicated by the presence of persistent mismatch demonstrated by ventilation-perfusion lung scans. The likely mechanism underlying this phenomenon is discussed.

Reduction in myocardial infarct size by basic fibroblast growth factor after temporary coronary occlusion in a canine model.

BACKGROUND: Basic fibroblast growth factor (bFGF) has been shown to reduce infarct size in canine acute myocardial infarction; however, the mechanism of tissue salvage remains uncertain. We evaluated the effect of bFGF on infarct size in a model of acute infarction in which coronary occlusion was followed by prolonged reperfusion and sought to determine whether reperfusion attenuates the stimulus for myocardial neovascularization. METHODS AND RESULTS: Anesthetized dogs undergoing 4-hour balloon occlusion of the left anterior descending coronary artery were treated with intracoronary bFGF (n = 8) or vehicle (n = 6). Ten-microgram doses of bFGF were administered 10 minutes after occlusion and again immediately before reperfusion. Left ventriculograms were obtained before occlusion, after reperfusion, and preceding euthanasia on day 7. Infarct size, expressed as a percentage of the area at risk, was reduced in bFGF-treated dogs (13.7 +/- 2.1% versus 28 +/- 3.4%; P = .002). Changes in left ventricular ejection fraction, capillary density, and cellular proliferation-assessed immunohistochemically with factor VIII and proliferating cell nuclear antigen antibodies-were similar in both groups. To assess coronary vasomotor responses to bFGF, a separate hemodynamic study was performed in five anesthetized nonischemic dogs in which incremental bFGF doses up to 100 micrograms induced no vasodilator response. CONCLUSIONS: Treatment with bFGF was associated with a reduction in infarct size without hemodynamic effects or evidence of neovascularization. These data suggest that bFGF mediates myocardial salvage independently of angiogenesis and that reperfusion after infarction may attenuate the stimulus for neovascularization.

Rationale for local drug delivery.

Although advances during the last decade have transformed the management of coronary artery disease, deficiencies in our understanding of the basic processes of arterial thrombosis and restenosis after percutaneous intervention continue to present major challenges to their prevention. While coronary stenting has in selected cases provided the first effective approach to the problem of restenosis, new devices such as atherectomy have largely proven ineffective in this field. Similarly, despite evidence that many pharmacological agents reduce neointimal hyperplasia in experimental models, in clinical trials these agents have failed to attenuate the restenotic process. This may reflect patients' inability to tolerate the high systemic drug concentrations required to achieve adequate levels for sufficient time at the target site, necessitating a shift in the focus of therapeutic agents for the prevention of thrombosis and restenosis to local or site-specific delivery. The major advantage that local drug delivery may potentially provide is the ability to achieve high and sustained local concentrations of drug without large systemic doses, thus minimizing systemic toxicity.

Direct angioplasty in acute myocardial infarction. State of the art and current controversies.

Although direct angioplasty may have been undervalued in the past, its utility in the treatment of acute coronary occlusion is now firmly established, and it unquestionably will remain an integral component of myocardial reperfusion therapy. As refinements in angioplasty equipment, cardiovascular support techniques, and adjunctive therapy occur, the challenge facing cardiologists in the 1990s will be to define the most effective role for direct angioplasty in the treatment of acute myocardial infarction.

Dual chamber rate responsive pacing to allow sotalol therapy for ventricular tachycardia.

In order to allow the use of sotalol to control ventricular tachycardia (VT), dual chamber rate responsive (DDDR) pacemakers were implanted in ten patients aged 6 to 73 years (mean 50 years). Nine presented with monomorphic VT (seven inducible at baseline electrophysiological study [EPS]) and one with syncope (monomorphic VT at EPS). On sotalol, VT was initiated in only one. This patient received sotalol in the absence of an effective alternative agent. The mean dose was 468 +/- 269 mg/day. Indications for pacing were symptomatic sotalol induced bradycardia (7), sinus node dysfunction (1), postoperative complete heart block (1), and infra-His block at baseline EPS (1). At least five of these patients would have been candidates for an implantable cardioverter defibrillator had sotalol required discontinuation. Initially, nine patients were paced in DDDR mode and one, with normal AV conduction on sotalol, in AAIR. One patient was unable to tolerate sotalol despite pacing. One patient died suddenly after 35 months of symptom-free follow-up. There was a significant improvement in symptomatic status (P = 0.03) after pacing among the other eight patients with no recurrence of VT. The implantation of a DDDR pacemaker may be indicated in selected patients with serious cardiac arrhythmias. With such a device programmed to an appropriate mode, sotalol can be used successfully where otherwise contraindicated by bradycardia or preexisting conduction disease. For some patients this may obviate the expense, inconvenience, and attendant risks of implantable cardioverter defibrillator implantation.