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Presents a review of current information on diastolic dysfunction in congestive heart failure from seminars in medicine of the Beth Israel Hospital, Boston, Mass. Hypertrophy and diastolic heart failure; Ventricular remodeling and diastolic heart failure; Cellular mechanisms of diastolic dysfunction; Clinical implications.

Background: Percutaneous balloon mitral valvuloplasty is known to produce short-term hemodynamic and symptomatic improvement in many patients with mitral stenosis. Comprehensive assessment of the clinical usefulness of balloon valvuloplasty requires evaluation of patients' long-term outcomes., Methods: We performed balloon mitral valvuloplasty in 146 patients between October 1, 1985, and October 1, 1991. Base-line demographic, clinical, echocardiographic, and hemodynamic variables were evaluated in order to identify predictors of long-term event-free survival., Results: Balloon mitral valvuloplasty was completed successfully in 136 (93 percent) of the patients in whom the procedure was attempted; it resulted in an increase in the mean (+/- SD) mitral-valve area from 1.0 +/- 0.4 to 2.1 +/- 0.9 cm2 and a decrease in the mean transmitral pressure gradient from 14 +/- 5 to 6 +/- 3 mm Hg (P < 0.001 for both comparisons). The estimated overall five-year survival rate was 76 +/- 5 percent, and the estimated five-year event-free survival rate (the percentage of patients without mitral-valve replacement, repeat valvuloplasty, or death from cardiac causes) was 51 +/- 6 percent. According to multivariate Cox proportional-hazards analysis, the independent predictors of longer event-free survival were a lower mitral-valve echocardiographic score (a measure of mitral-valve deformity; range, 0 for a normal valve to 16 for a seriously deformed valve; P < 0.001), lower left ventricular end-diastolic pressure (P = 0.001), and a lower New York Heart Association (NYHA) functional class (P = 0.04). Patients with no risk factors for early restenosis or only one risk factor (echocardiographic score > 8, left ventricular end-diastolic pressure > 10 mm Hg, or NYHA functional class IV) had a predicted five-year event-free survival rate of 60 to 84 percent, whereas patients with two or three risk factors had a predicted five-year event-free survival rate of only 13 to 41 percent., Conclusions: Balloon mitral valvuloplasty as a treatment for selected patients with mitral stenosis has good long-term results. The long-term outcome after this procedure can be predicted on the basis of patients' base-line characteristics.

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.

Prostaglandins may be important regulators of coronary blood flow. To investigate this possibility, we studied the effect of blockade of prostaglandin synthesis by indomethacin in nine patients with coronary-artery disease. Coronary-sinus blood flow (determined with the thermodilution technique) was recorded, together with mean arterial blood pressure and the myocardial arteriovenous oxygen difference from simultaneously obtained arterial and coronary-sinus blood samples, before and 20 minutes after an intravenous dose of indomethacin (0.5 mg per kilogram of body weight). There were significant increases (P less than 0.05) in mean arterial pressure (from 99 +/- 4 to 118 +/- 5 mm Hg [+/- S.E.M.]), coronary vascular resistance (+73 per cent), and myocardial arteriovenous oxygen difference (from 107 +/- 5 to 138 +/- 4 ml per liter) after indomethacin, but coronary blood flow fell significantly, from 181 +/- 29 to 111 +/- 14 ml per minute (P less than 0.05). Thus, despite an increase in myocardial oxygen demand, coronary blood flow fell and coronary vascular resistance increased. This coronary vasoconstrictor effect may have been due to blockade of vasodilatory prostaglandin synthesis or to a direct drug effect. Whatever the mechanism, indomethacin should be used with caution in patients with severe coronary-artery disease.

Nine patients who underwent aortic-valve replacement for acute aortic regurgitation due to infective endocarditis were studied for clinical features that may be useful in assessing the severity of this condition. The traditional physical signs of a wide pulse pressure were absent. As compared to a group of patients with chronic aortic regurgitation, the mean (plus or minus S.D.) pulse pressure (55 plus or minus 7 vs. 105 plus or minus 22 mm Hg), left ventricular end diastolic volume (146 plus or minus 28 vs. 264 plus or minus 64 ml per square meter) and stroke volume (89 plus or minus 22 vs. 163 plus or minus 57 ml per square meter) were significantly smaller in the acute group (P less than 0.01). Left ventricular pressure exceeded left atrial pressure in late diastole, causing premature closure of the mitral valve, and the degree of early closure reflected the increase in left ventricular end diastolic pressure. Premature closure of the mitral valve was demonstrated by echocardiography in all patients. Those with echocardiographic signs of very early mitral-valve closure have severely volume-overloaded ventricles and are candidates for early valve replacement.

Nine patients with acute myocardial infarction had cardiac catheterization and intracoronary infusions of streptokinase 2.3 to 4.3 hours (mean, 3.5) after the onset of symptoms. Occluded coronary arteries were opened within approximately 20 minutes in all patients, but reocclusion occurred in one patient. The immediate effect of thrombolysis on myocardial salvage was assessed with the intracoronary injection of thallium-201. Improved regional perfusion, indicating myocardial salvage after recanalization, was observed in seven of the nine patients. One patient, who had also sustained a nontransmural infarction one week before, had no change after thrombolysis. In the ninth patient, recanalization of a coronary artery was followed by reocclusion and worsening of the myocardial-perfusion defect. Intracoronary thallium-201 studies two weeks and three months after streptokinase infusion in two patients were unchanged in comparison with scintiscans performed 1.5 hours after thrombolysis. These short-term observations suggest that recanalization of obstructed coronary arteries after intracoronary thrombolysis can salvage jeopardized myocardium, However, evaluation of the long-term effects of this procedure on survival and myocardial function will require controlled clinical trials.

To assess possible coronary vasoconstriction in patients with ischemic heart disease, we measured coronary vascular resistance in 12 patients with normal hearts and 12 with coronary disease before and during the initial 50 seconds of cold pressor test, a stimulus known to produce systemic vasoconstriction. Control coronary vascular resistance was similar in the two groups, and although it did not change in patients with normal vessels, it rose by 27 per cent (P less than 0.005) in the group with coronary disease during the cold pressor test. In three of 12 patients with coronary disease coronary flow actually declined despite an increase in arterial pressure; in four, angina was precipitated. Phentolamine abolished increases in arterial pressure and coronary vascular resistance during the test in three patients with coronary disease. Adrenergically mediated coronary vascular tone may be an important determinant of coronary blood flow and may contribute to ischemia in patients with coronary disease.

We measured creatine kinase activity, isozyme composition, and total creatine content in biopsy samples of left ventricular myocardium from 34 adults in four groups: subjects with normal left ventricles, patients with left ventricular hypertrophy due to aortic stenosis, patients with coronary artery disease without left ventricular hypertrophy, and patients with coronary artery disease and left ventricular hypertrophy due to aortic stenosis. As compared with specimens of normal left ventricles, those from all patients with left ventricular hypertrophy had lower creatine kinase activity, higher MB creatine kinase isozyme content and activity, and lower creatine content. Specimens from the patients without left ventricular hypertrophy had normal creatine kinase activity, increased MB creatine kinase isozyme content and activity, and decreased total creatine content. The normal ventricles showed almost no MB isozyme content or activity. These data suggest that changes in the creatine kinase system occur in both pressure-overload hypertrophy and coronary artery disease. Patients with myocardial infarction who have mild or no preexisting fixed coronary artery disease or pressure-overload hypertrophy would not be expected to have elevation of serum MB creatine kinase.

Amrinone, a new bipyridine derivative, exerts a positive inotropic action in experimental preparations and is effective when administered orally to dogs. To assess its immediate effects in man, we studied by cardiac catheterization the hemodynamic responses to amrinone (1.85 to 3.5 mg per kilogram given intravenously) in eight patients with congestive heart failure already receiving full doses of digitalis. the following statistically significant (P less than 0.01) effects were noted: cardiac index increased from a mean +/- 1 S.D. of 1.8 +/- 0.3 to 2.6 +/- 0.3 liters per minute per square meter; peak rate of left ventricular pressure rise rose from 849 +/- 233 to 1206 +/- 456 mm Hg per second; left ventricular end-diastolic pressure fell from 25 +/- 9 to 14 +/- 7 mm Hg; pulmonary-capillary pressure fell from 28 +/- 8 to 15 +/- 4 mm Hg; and right atrial pressure fell from 12 +/- 6 to 7 +/- 5 mm Hg. Mean heart rate was unchanged, and aortic mean pressure declined slightly (86 +/- 10 to 80 +/- 7 mm Hg, P less than 0.025). No toxicity was observed. Amrinone, whose mechanism of action has not yet ben defined, warrants further study as a possible treatment for heart failure.