Defective adenosine triphosphate synthesis. An explanation for skeletal muscle dysfunction in phosphate-deficient mice.

The basis for skeletal muscle dysfunction in phosphate-deficient patients and animals is not known, but it is hypothesized that intracellular phosphate deficiency leads to a defect in ATP synthesis. To test this hypothesis, changes in muscle function and nucleotide metabolism were studied in an animal model of hypophosphatemia. Mice were made hypophosphatemic through restriction of dietary phosphate intake. Gastrocnemius function was assessed in situ by recording isometric tension developed after stimulation of the nerve innervating this muscle. Changes in purine nucleotide, nucleoside, and base content of the muscle were quantitated at several time points during stimulation and recovery. Serum concentration and skeletal muscle content of phosphorous are reduced by 55 and 45%, respectively, in the dietary restricted animals. The gastrocnemius muscle of the phosphate-deficient mice fatigues more rapidly compared with control mice. ATP and creatine phosphate content fall to a comparable extent during fatigue in the muscle from both groups of animals; AMP, inosine, and hypoxanthine (indices of ATP catabolism) appear in higher concentration in the muscle of phosphate-deficient animals. Since total ATP use in contracting muscle is closely linked to total developed tension, we conclude that the comparable drop in ATP content in association with a more rapid loss of tension is best explained by a slower rate of ATP synthesis in the muscle of phosphate-deficient animals. During the period of recovery after muscle stimulation, ATP use for contraction is minimal, since the muscle is at rest. In the recovery period, ATP content returns to resting levels more slowly in the phosphate-deficient than in the control animals. In association with the slower rate of ATP repletion, the precursors inosine monophosphate and AMP remain elevated for a longer period of time in the muscle of phosphate-deficient animals. The slower rate of ATP repletion correlates with delayed return of normal muscle contractility in the phosphate-deficient mice. These studies suggest that the slower rate of repletion of the ATP pool may be the consequence of a slower rate of ATP synthesis and this is in part responsible for the delayed recovery of normal muscle contractility.

Operator volume and outcomes in 12,998 percutaneous coronary interventions. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to determine whether there is a relation between operator volume and outcomes for percutaneous coronary interventions (PCIs). BACKGROUND: A 1993 American College of Cardiology/American Heart Association task force stated that cardiologists should perform > or = 75 procedures/year to maintain competency in PCIs; however, there were limited data available to support this statement. METHODS: Data were collected from 1990 through 1993 on 12,988 PCIs (12,118 consecutive hospital admissions) performed by 31 cardiologists at two hospitals in New Hampshire and two in Maine and one hospital in Massachusetts supporting these procedures. Operators were categorized into terciles based on annualized volume of procedures. Univariate and multivariate regression analyses were used to control for case-mix. Successful outcomes included angiographic success (all lesions attempted dilated to < 50% residual stenosis) and clinical success (at least one lesion dilated to < 50% residual stenosis and no adverse outcomes). In-hospital adverse outcomes included coronary artery bypass graft surgery (CABG), myocardial infarction (MI) and death. RESULTS: After adjustment for case-mix, higher angiographic (low, middle and high terciles: 84.7%, 86.1% and 90.3%, p-trend 0.006) and clinical success rates (85.8%, 88.0% and 90.7%, p-trend 0.025), with fewer referrals to CABG (4.54%, 3.75% and 2.49%, p-trend <0.001), were seen as operator volume increased. There was a trend toward higher MI rates for high volume operators (2.00%, 1.98% and 2.57%, p-trend 0.06); all terciles had similar in-hospital mortality rates (1.09%, 0.96% and 1.05%, p-trend 0.8). CONCLUSIONS: There is a significant relation between operator volume and outcomes in PCIs. Efforts should be directed toward understanding why high volume operators are more successful and encounter fewer adverse outcomes.

Changing outcomes in percutaneous coronary interventions: a study of 34,752 procedures in northern New England, 1990 to 1997. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to evaluate the changing outcomes of percutaneous coronary interventions (PCIs) in recent years. BACKGROUND: The field of interventional cardiology has seen considerable growth in recent years, both in the number of patients undergoing procedures and in the development of new technology. In view of recent changes, we evaluated the experience of a large, regional registry of PCIs and outcomes over time. METHODS: Data were collected from 1990 to 1997 on 34,752 consecutive PCIs performed at all hospitals in Maine (two), New Hampshire (two) and Vermont (one) supporting these procedures, and one hospital in Massachusetts. Univariate and multivariate regression analyses were used to control for case mix. Clinical success was defined as at least one lesion dilated to <50% residual stenosis and no adverse outcomes. In-hospital adverse outcomes included coronary artery bypass graft surgery (CABG), myocardial infarction and mortality. RESULTS: Over time, the population undergoing PCIs tended to be older with increasing comorbidity. After adjustment for case mix, clinical success continued to improve from a low of 88.2% in earlier years to a peak of 91.9% in recent years (p trend <0.001). The rate of emergency CABG after PCI fell in recent years from a peak of 2.3% to 1.3% (p trend <0.001). Mortality rates decreased slightly from 1.2% to 1.1% (p trend 0.007). CONCLUSIONS: There has been a significant improvement in clinical outcomes for patients undergoing PCIs in northern New England, including a significant decline in the need for emergency CABG.

Multivariate prediction of in-hospital mortality after percutaneous coronary interventions in 1994-1996. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: Using recent data, we sought to identify risk factors associated with in-hospital mortality among patients undergoing percutaneous coronary interventions. BACKGROUND: The ability to accurately predict the risk of an adverse outcome is important in clinical decision making and for risk adjustment when assessing quality of care. Most clinical prediction rules for percutaneous coronary intervention (PCI) were developed using data collected before the broader use of new interventional devices. METHODS: Data were collected on 15,331 consecutive hospital admissions by six clinical centers. Logistic regression analysis was used to predict the risk of in-hospital mortality. RESULTS: Variables associated with an increased risk of in-hospital mortality included older age, congestive heart failure, peripheral or cerebrovascular disease, increased creatinine levels, lowered ejection fraction, treatment of cardiogenic shock, treatment of an acute myocardial infarction, urgent priority, emergent priority, preprocedure insertion of an intraaortic balloon pump and PCI of a type C lesion. The receiver operating characteristic area for the predicted probability of death was 0.88, indicating a good ability to discriminate. The rule was well calibrated, predicting accurately at all levels of risk. Bootstrapping demonstrated that the estimate was stable and performed well among different patient subsets. CONCLUSIONS: In the current era of interventional cardiology, accurate calculation of the risk of in-hospital mortality after a percutaneous coronary intervention is feasible and may be useful for patient counseling and for quality improvement purposes.

Cardiac involvement in myotonic muscular dystrophy.

Cardiac illness in myotonic muscular dystrophy (MyD) is infrequent, but subclinical cardiac involvement in MyD is very common (found in 42 of 46 subjects) and may be responsible for sudden death. In this series, we found ECG abnormalities in 72%, left ventricular dysfunction in 70%, mitral valve prolapse in 37%, and sudden death in 4%. Four deaths during the study period were due to acute left ventricular failure, one to sepsis and respiratory insufficiency, and one was unexplained. We did not find ominous bradyarrhythmias or atrioventricular block, evidence of congestive heart failure, noninvasive evidence of coronary artery disease, or any correlation of type or amount of cardiac involvement with any clinical parameter such as age, sex, or severity of systemic dystrophy. We feel tachyarrhythmias may play as important a role in sudden death of myotonic muscular dystrophy subjects as bradyarrhythmias, and coronary artery disease in addition to cardiac dystrophy may produce arrhythmias and myocardial dysfunction in myotonic muscular dystrophy. In addition, some subjects have an unusual form of resting left ventricular dysfunction which improves with exercise. The most important problem in the clinical management of myotonic muscular dystrophy subjects is sudden death, and the solution does not appear to be empiric ventricular pacing. Our recommendations for prophylaxis of sudden death in myotonic muscular dystrophy are noninvasive investigation of coronary artery disease in subjects with significant risk factors, with angiography and surgery if indicated: detailed evaluation of syncopal and presyncopal events, including electrophysiologic testing, with pacemaker or antiarrhythmic drug therapy if indicated; and consideration of ventricular pacing of asymptomatic subjects if severe bradycardia or marked intraventricular conduction delay develops during follow-up, serial 12-lead ECGs. The documentation of tachyarrhythmias during sudden death and syncopal episodes in myotonic muscular dystrophy subjects makes ventricular pacing alone an uncertain modality for prevention of sudden death in subjects with only mildly lengthened PR or QRS intervals, and suggests a combination of pacemaker and antiarrhythmic drug therapy for the myotonic muscular dystrophy subject with syncope of no apparent cause.

Improvement in mitral regurgitation after aortic valve replacement.

This study sought to determine whether there is a quantitative improvement in mitral regurgitation (MR) after aortic valve replacement (AVR) for aortic stenosis (AS) and, if so, the mechanisms for this change. MR frequently accompanies AS. The addition of mitral valve replacement to AVR significantly increases the risk of surgery. Although previous studies have suggested a qualitative improvement in MR severity after AVR, semiquantitative analysis of this improvement has not been documented nor have the underlying mechanisms been examined. We evaluated 28 patients who had undergone 2-dimensional echo and color flow Doppler imaging an average of 1.5 +/- 2.5 months before and 2.5 +/- 4.2 months after AVR. Maximum MR area, MR percentage (MR area/left atrial area), mitral annular area, left atrial area, aortic gradient, and parameters of left ventricular geometry were measured to evaluate MR severity and to assess functional mechanisms for improvement in MR. There was a significant decrease in MR area (5.5 +/- 2.8 cm2 vs 2.5 +/- 1.9 cm2, p < or =0.0001) and MR percentage (25 +/- 11% vs 12 +/- 10% after operation, p < or =0.0001) between preoperative and postoperative studies. There was a significant reduction in aortic gradient, mitral annular area, left atrial area, and left ventricular length postoperatively. In univariate analysis, MR improvement was related to the lower preoperative left ventricular fractional area change (p = 0.027) and to the changes in fractional area change (p = 0.001) and left ventricular systolic area (p = 0.001). Thus, improvement in MR after AVR is related to changes in left ventricular function postoperatively. These data suggest that reduction in MR is due not only to decreased intraventricular pressure, but also to changes in ventricular morphology.

Results of directional coronary atherectomy in Northern New England. Northern New England Cardiovascular Disease Study Group.

The role of directional coronary atherectomy (DCA) in interventional cardiology remains uncertain. We report the Northern New England regional experience with DCA from 1991 to 1994. Data were collected on 11,178 patients having had an intervention on a single lesion in a single vessel (798 DCAs; 10,380 percutaneous transluminal angioplasties [PTCA]). The use of DCA increased from 1.8% of interventions in 1991 to 10% in 1994. Compared with PTCA, DCA patients were younger, more often men, had more 1-vessel disease and more coronary artery bypass surgery (CABG). DCA was more often used in the left anterior descending artery, in vein grafts, for restenoses, for subtotal occlusions, and with type A lesions. Angiographic success (96.7%) and clinical success (93%) were good. Adverse events were rare: mortality 0.9%, emergent CABG 2.2%, nonfatal myocardial infarction 2.8%. After adjusting for case-mix, there was no difference between DCA and PTCA for in-hospital mortality (odds ratio [OR] = 1.03, 95% confidence interval [CI] 0.44 to 2.43, p = 0.95) or need for emergent CABG (OR = 1.27, 95% CI 0.77 to 2.10, p = 0.34). Atherectomy patients were more likely to have a nonfatal myocardial infarction (OR = 2.0, 95% CI 1.26 to 3.20, p <0.01), to sustain an injury to the femoral or brachial artery (OR = 2.89, 95% CI 1.52 to 5.51, p <0.01), and to have a clinically successful procedure (OR = 1.37, 95% CI 1.01 to 1.88, p = 0.05). Our results support the relative safety and effectiveness of DCA as its use disseminated into the region.

Safety and efficacy of percutaneous coronary interventions performed immediately after diagnostic catheterization in northern new england and comparison with similar procedures performed later.

"Ad hoc" percutaneous coronary interventions (PCIs)-those performed immediately after diagnostic catheterization-have been reported in earlier studies to be safe with a suggestion of higher risk in certain subgroups. Despite increasing use of this strategy, no data are available in recent years with new device technology. We studied use of an ad hoc strategy in a large regional population to determine its use and outcomes compared with staged procedures. A database from the 6 centers performing PCIs in northern New England and 1 center in Massachusetts was analyzed. During 1997, excluding only patients requiring emergency procedures or those with a prior PCI, 4,136 PCIs were performed, 1,748 (42.3%) of these being ad hoc procedures. Patients having ad hoc procedures were less likely to have peripheral vascular disease, renal failure, prior myocardial infarction, or coronary artery bypass surgery, congestive heart failure, or poor left ventricular function, and more likely to have received preprocedural intravenous heparin or nitroglycerin or to have required an urgent procedure. Narrowings treated during ad hoc procedures were less frequently types B and C or in saphenous vein grafts. Adjusted rates of clinical success were not different between ad hoc and non-ad hoc procedures (93.7% vs 93.6%); there was no difference in the incidence of death (0.6% vs 0.5%), emergency (0. 9% vs 0.8%) or any (1.4% vs 0.8%) coronary artery bypass surgery, or myocardial infarction (2.6% vs 2.0%). As currently practiced in our region, ad hoc intervention is used selectively with outcomes similar for ad hoc and non-ad hoc procedures.

Severe congestive heart failure and cardiomyopathy as a complication of myotonic dystrophy in pregnancy.

The pregnancy of a patient with myotonic dystrophy and heart failure due to cardiac involvement is described. Endomyocardial biopsy was performed at 32 weeks' gestation with echocardiographic guidance to establish the diagnosis. Severe congestive heart failure, refractory to conventional therapy, was encountered. Continuous arteriovenous hemofiltration was used to relieve pulmonary edema before cesarean delivery.

Giant cell arteritis in a black patient.

Giant cell arteritis has been thought to occur only in white patients. There have been several recent reports of this disorder to blacks, however, and this case of biopsy-proven giant cell arteritis in a black patient indicates the diagnosis should be considered in any elderly patient with typical symptoms regardless of race.

Cause of in-hospital death in 12,232 consecutive patients undergoing percutaneous transluminal coronary angioplasty. The Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Some deaths after percutaneous coronary angioplasty (PTCA) occur in high-risk situations (eg, shock), whereas others are unexpected and related to procedural complications. To better describe the epidemiologic causes of death after PTCA, we undertook a systematic review of all in-hospital PTCA deaths in Northern New England from 1990 to 1993. METHODS: The medical records of 121 patients who died during their acute hospitalization for PTCA were reviewed with a standardized data extraction tool to determine a mode of death (eg, low output failure, arrhythmia, respiratory failure) and a circumstance of death (eg, death attributable to a procedural complication, preexisting acute cardiac disease). Any death not classified as a procedural complication was reviewed by a committee and the circumstance of death assigned by a majority rule. RESULTS: Low-output failure was the most common mode of death occurring in 80 (66.1%) of 121 patients. Other modes of death included ventricular arrhythmias (10.7%), stroke (4.1%), preexisting renal failure (4.1%), bleeding (2.5%), ventricular rupture (2.5%), respiratory failure (2.5%), pulmonary embolism (1.7%), and infection (1.7%). The circumstance of death was a procedural complication in 65 patients (53.7%) and a preexisting acute cardiac condition in 41 patients (33.9%). Women were more likely to die of a procedural complication than were men. CONCLUSION: Procedural complications account for half of all post-PTCA deaths and are a particular problem for women. Other deaths are more directly related to patient acuity or noncardiac, comorbid conditions. Understanding why women face an increased risk of procedural complications may lead to improved outcomes for all patients.