Right ventricular contractility in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension.

Since systemic sclerosis (SSc) also involves the heart, the aim of the present study was to evaluate possible differences in right ventricular (RV) pump function between SSc-associated pulmonary arterial hypertension (PAH; SScPAH) and idiopathic PAH (IPAH). In 13 limited cutaneous SScPAH and 17 IPAH patients, RV pump function was described using the pump function graph, which relates mean RV pressure ((RV)) and stroke volume index (SVI). Differences in pump function result in shift or rotation of the pump function graph. (RV) and SVI were measured using standard catheterisation. The hypothetical isovolumic (RV) ((RV,iso)) was estimated using a single-beat method. The pump function graph was approximated by a parabola: (RV) = (RV,iso)[1-(SVI/SVI(max))(2)], where SVI(max )is the hypothetical maximal SVI at zero (RV), enabling calculation of SVI(max). There were no differences in SVI and SVI(max). Both (RV) and (RV,iso) were significantly lower in SScPAH than in IPAH ((RV) 30.7+/-8.5 versus 41.2+/-9.4 mmHg; (RV,iso) 43.1+/-12.4 versus 53.5+/-10.0 mmHg). Since higher pressures were found at similar SVI, the difference in the pump function graph results from lower contractility in SScPAH than in IPAH. Right ventricular contractility is lower in systemic sclerosis-associated pulmonary arterial hypertension than in idiopathic pulmonary arterial hypertension.

Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy.

BACKGROUND: Patients with heart failure have modified myocardial expression of nitric oxide synthase (NOS), as is evident from induction of calcium-insensitive NOS isoforms. The functional significance of this modified NOS gene expression for left ventricular (LV) contractile performance was investigated in patients with dilated nonischemic cardiomyopathy. METHODS AND RESULTS: In patients with dilated, nonischemic cardiomyopathy, invasive measures of LV contractile performance were derived from LV microtip pressure recordings and angiograms and correlated with intensity of gene expression of inducible (NOS2) and constitutive (NOS3) NOS isoforms in simultaneously procured LV endomyocardial biopsies (n=20). LV endomyocardial expression of NOS2 was linearly correlated with LV stroke volume (P=0.001; r=0.66), LV ejection fraction (P=0.007; r=0.58), and LV stroke work (P=0.003; r=0.62). In patients with elevated LV end-diastolic pressure (>16 mm Hg), a closer correlation was observed between endomyocardial expression of NOS2 and LV stroke volume (P=0.001; r=0.74), LV ejection fraction (P=0.0007; r=0.77), and LV stroke work (r=0.82; P=0.0002). LV endomyocardial expression of NOS3 was linearly correlated with LV stroke volume (P=0.01; r=0.53) and LV stroke work (P=0.01; r=0.52). To establish the role of nitric oxide (NO) as a mediator of the observed correlations, substance P (which causes endothelial release of NO) was infused intracoronarily (n=12). In patients with elevated LV end-diastolic pressure, an intracoronary infusion of substance P increased LV stroke volume from 72+/-13 to 91+/-16 mL (P=0.06) and LV stroke work from 67+/-11 to 90+/-15 g. m (P=0.03) and shifted the LV end-diastolic pressure-volume relation to the right. CONCLUSIONS: In patients with dilated cardiomyopathy, an increase in endomyocardial NOS2 or NOS3 gene expression augments LV stroke volume and LV stroke work because of a NO-mediated rightward shift of the diastolic LV pressure-volume relation and a concomitant increase in LV preload reserve.

High dose bolus heparin as initial therapy before primary angioplasty for acute myocardial infarction: results of the Heparin in Early Patency (HEAP) pilot study.

OBJECTIVES: We sought to determine the effect of high dose intravenous bolus heparin on early coronary patency before primary angioplasty. BACKGROUND: Early coronary angiography after thrombolysis for acute myocardial infarction has shown better patency when intravenous heparin is used as an adjunct. The present study explores whether heparin alone can induce reperfusion. METHODS: In the Heparin in Early Patency (HEAP) pilot study, 108 patients with signs and symptoms of acute myocardial infarction < 6 h eligible for primary angioplasty received a single intravenous bolus of 300 U/kg of heparin together with aspirin (160 mg chewed) in the emergency room. The median dose of bolus heparin given was 27,000 U. Patency of the infarct-related artery (IRA) was assessed by coronary angiography at a median of 85 min after the heparin bolus. RESULTS: In 55 patients (51%, 95% confidence interval 38% to 64%), Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 was observed at 90 min: TIMI flow grade 3 in 33 patients (31%); TIMI flow grade 2 in 22 (20%). Thirty-two (64%) of 50 patients with symptoms < or = 2 h had TIMI flow grade 2 or 3 versus 23 (40%) of 58 patients with symptoms > 2 h (p = 0.02). No significant bleeding was seen. Two patients (2%) died in the hospital. The patency results obtained in patients treated with the high dose bolus heparin were compared with those in 108 patients from a large primary angioplasty database, who were treated with standard therapy, including aspirin but not intravenous heparin, and were matched for clinical and angiographic characteristics with the HEAP pilot study patients. They showed an 18% patency rate (p < 0.001) of the IRA (TIMI flow grade 3 in 9%, TIMI flow grade 2 in 9%) before primary angioplasty. CONCLUSIONS: Early therapy with high dose heparin is associated with full coronary reperfusion in a considerable number of patients with acute myocardial infarction, especially in those treated early (< 2 h). This simple, inexpensive, probably safe and easily antagonizable treatment may be an attractive first treatment of acute myocardial infarction both before and during the hospital stay in conjunction with primary angioplasty.

Dutch guidelines for interventional cardiology: institutional and operator competence and requirements for training.

Interventional cardiology is an expanding field within cardiovascular medicine and today it is generally accepted that cardiologists require specific training, knowledge and skills. Hospitals where coronary interventions are performed must be properly equipped and able to provide specialised care. Percutaneous coronary interventions are frequently used for coronary revascularisation. The public should have confidence in the uniformity of high quality care. Therefore, such quality of care should be maintained by certification of the individual operators, general guidelines for institutional requirements and formal audits. The Netherlands Society of Cardiology (NVVC) will be implementing a new registration system for cardiologists with a subspecialisation that will include registration for interventional cardiology. The NVVC asked the Working Group of Interventional Cardiology (WIC) to update the 1994 Dutch guidelines on operator and institutional competence, and requirements for training in interventional cardiology in order to incorporate them into the official directives. The present guidelines represent the expert opinion of the Dutch interventional cardiology community and are in accordance with international regulations. After two rounds of discussion, the NVVC approved the guidelines in November 2004 during the autumn meeting.

Noninvasive assessment of right ventricular diastolic function by electrical impedance tomography.

STUDY OBJECTIVES: Electrical impedance tomography (EIT) offers the possibility to study blood volume changes within the right atrium during the cardiac cycle. The aim of this study was to determine the applicability of EIT in the assessment of right ventricular diastolic function in COPD. DESIGN: By means of region of interest analysis, impedance changes within the right atrium during the cardiac cycle were plotted as a function of time. As a diastolic index of the right ventricle, the right atrium emptying volume (RAEV), defined as the ratio between the volume change during the rapid filling phase relative to the total ventricular filling volume, was calculated. In a first study, the validity of the EIT method was assessed by comparison of the RAEV measured by EIT and MRI in a group of eight patients with severe COPD and seven control subjects. A second study was undertaken to assess the relation between RAEV and pulmonary artery pressure in a group of 27 patients measured by right-sided heart catheterization. RESULTS: The correlation coefficient between RAEV measured with MRI and EIT was 0.78. The difference between RAEV measured by MRI and EIT was 8.3 +/- 15.7% (mean +/- SD) for the control subjects and 3.5 +/- 10.9% for the COPD patients. RAEV values measured by EIT and MRI were larger in the control group (47.1 +/- 7.6%) compared with the patient group (38.1 +/- 10.4%). There was a clear nonlinear relationship between RAEV and the pulmonary artery pressure (y = 315 x-0.64, r = 0.83, p < 0.001). CONCLUSION: Our results indicate that RAEV measured by EIT is a useful noninvasive and inexpensive method for assessing right ventricular diastolic function in COPD patients.

The effect of renal transplantation on hyperhomocysteinaemia in dialysis patients, and the estimation of renal homocysteine extraction in patients with normal renal function.

BACKGROUND: The pathophysiology of hyperhomocysteinaemia in chronic renal failure (CRF) is unknown. Possible mechanisms are decreased renal homocysteine (Hcy) catabolism or inhibition of extrarenal Hcy metabolism by uraemic toxins. METHODS: We studied the short-term effect on plasma Hcy concentration of improvement of renal function after successful kidney transplantation (n = 8), and determined renal Hcy extraction by measurement of total Hcy in arterial and renal venous blood in 7 cardiac patients with normal renal function. RESULTS: Post-transplantation, plasma Hcy decreased with improving renal function. In the cardiac patients, no significant renal Hcy extraction could be demonstrated, but tubular disposal of the filtered load could not be excluded. CONCLUSIONS: Because loss of such renal metabolism could lead to hyperhomocysteinaemia in CRF, it is necessary to determine the renal extraction of free Hcy in subjects with normal renal function to further investigate renal homocysteine metabolism.

Determination of stroke volume by means of electrical impedance tomography.

ECG-gated electrical impedance tomography (EIT) is a non-invasive imaging technique, developed to monitor blood volume changes. This study is the first in comparing this non-invasive technique in measuring stroke volume with established techniques. The objective of this study was to validate EIT variables derived from the EIT images with paired obtained stroke volume measurements by thermodilution and MRI. After right cardiac catheterization, EIT measurements were performed in 25 patients. Regression analysis was used to analyse the relation between the EIT results and stroke volume determined by thermodilution. From the regression line an equation was derived to estimate stroke volume (in ml) by EIT. A strong correlation was found between EIT and stroke volume measured by the thermodilution method (r = 0.86). In a group of 11 healthy subjects this equation was validated to MRI. The mean and standard deviation of the difference between EIT and MRI was 0.7 ml and 5.4 ml respectively. These data indicate that EIT is a valid and reproducible method for the assessment of stroke volume.

Epoprostenol-induced pulmonary vasodilatation in patients with pulmonary hypertension measured by electrical impedance tomography.

Electrical impedance tomography (EIT) has been proposed as a method to monitor dynamic changes in the pulmonary vascular bed. In this study we examined the validity of EIT in the measurement of pulmonary vasodilatation in eight patients with primary and secondary pulmonary hypertension when given the vasodilating agent epoprostenol (Flolan). Therefore, catheterization of the pulmonary artery was performed in the ICU and the cardiac output was measured by means of the Fick method. The pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) were determined. Epoprostenol was given in increasing doses to test reversibility of pulmonary hypertension. The maximum test dose was 12 ng kg(-1) min(-1). During each step simultaneous EIT (DAS-01 P Portable Data Acquisition System, Sheffield, England) measurements were performed with the 16 electrodes equidistantly positioned in the third intercostal space. The maximal systolic impedance change, relative to end-diastole, deltaZperf, was chosen as a measure of pulmonary perfusion. The impedance change between baseline and highest tolerable epoprostenol concentration was compared with the change in PVR. The mean PVR (dyn s/cm5) decreased from 636 (+/-399) to 366 (+/-242); p < 0.01. DeltaZperf (in arbitrary units) for the whole patient group increased from 901 (+/-295) x 10(-3) to 1082 (+/-472) x 10(-3) (p<0.05). Only one patient showed a reduction in pulmonary artery pressure >20%, which is defined as significant vasodilatation. A strong relationship was found between the impedance changes and the change in PVR and mPAP in the patient with a significant vasodilatation on epoprostenol. From these results we conclude that EIT is a reliable method to measure blood volume changes due to pharmacologically induced vasodilatation in the pulmonary bed.

[Diastolic heart failure]. / Diastolisch hartfalen.

Diastolic heart failure is predominantly a disease of the elderly: at the age of 70 years, almost half of all patients with heart failure have diastolic heart failure. Hypertension and obesity are common underlying disorders in patients with diastolic heart failure. Patients with diastolic heart failure have an equal, or only slightly better, prognosis in terms of mortality compared to patients with systolic heart failure. Echocardiography can distinguish diastolic heart failure from systolic heart failure. Patients with heart failure and a normal ejection fraction almost certainly have a diastolic dysfunction. There is a lack of reliable data about the optimal medicinal treatment strategy for patients with diastolic heart failure. Angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and (non-dihydropyridine) calcium antagonists have therapeutic potential. Digoxin may be contraindicated.

[Diagnosis of pulmonary hypertension: experiences with 187 patients referred to the VU Medical Center]. / Diagnostiek van pulmonale hypertensie: ervaringen bij 187 patiënten verwezen naar het VU Medisch Centrum.

OBJECTIVE: To describe the results of a multidisciplinary diagnostic protocol in patients referred due to suspected pulmonary hypertension. DESIGN: Descriptive. METHOD: In 187 patients who were referred to the VU Medical Centre, Amsterdam, the Netherlands, between May 1998 and February 2003, due to suspected pulmonary hypertension, the diagnosis was established by means of a multidisciplinary diagnostic protocol. The referral and final diagnoses were analysed, as well as the treatment the patients had received. RESULTS: In 56 patients (30%), the application of the protocol lead to a modification of the diagnosis; 16 patients (9%) were found not to have pulmonary hypertension; in 20 of the 89 patients referred with 'primary pulmonary hypertension' (48% of all referrals), an underlying disease was still identified: 6 cases of a connective tissue disease, 5 cases of a chronic thromboembolic process, 5 cases of a condition of the left heart, and 4 cases of an atrial septal defect. CONCLUSION: The diagnosis 'primary pulmonary hypertension' can only be made once all secondary types of the disease have been ruled out. The application of a multidisciplinary diagnostic protocol together with a contribution of specialists with specific expertise can help to adjust the initial diagnosis and sometimes even reject it.

A review of pulmonary arterial hypertension: Part 1. Novel insights and classification.

Pulmonary arterial hypertension (PAH) is a disease characterised by an increased pulmonary artery pressure. The precapillary pulmonary arteries show distinct pathobiological changes, i.e. medial hypertrophy, intimal fibrosis, microthrombi and plexiform lesions. Although the pathogenesis is not completely understood, pulmonary vascular proliferation and remodelling, due to a variety of mediators, is believed to play the pathogenetic key role. Genetic research reveals molecular deformities and gene mutations associated with phenotypic PAH. This article covers novel insights into pathobiology, pathogenesis and genes of PAH, which led to a novel classification system and a diagnostic work-up, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice in June 2003.

A review of pulmonary arterial hypertension: Part 2: Current and expected treatments.

Medical therapy for pulmonary arterial hypertension (PAH) focuses on pulmonary vascular remodelling and smooth muscle cell proliferation. This article covers the drugs which are approved or are in sight and the evidence-based treatment strategies that target the different pathobiological pathways, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice, June 2003. In addition we briefly look at the 'Venice consensus' on surgical treatment. In the past five and a half years more than 360 patients were seen for pulmonary hypertension in the Free University Medical Centre (VUmc). Present-day treatment, research studies and novel treatment strategies in the VUmc will be reviewed. Future treatments will be on the basis of insights into pathobiology, pathogenesis and genes in PAH and should focus on drug combinations, which theoretically target different or similar pathobiological pathways.

Patients with coronary stenosis and a fractional flow reserve of ≥0.75 measured in daily practice at the VU University Medical Center.

Objectives. The aim of this study was to analyse the rate of major adverse clinical events in patients with coronary artery disease and a fractional flow reserve (FFR) of ≥0.75 and deferred for coronary intervention in daily practice. Methods. From 1 January to 31 December 2006, FFR measurement was initiated in 122 patients (5%) out of 2444 patients referred for coronary angiography. In two patients FFR measurement failed and in one patient the FFR value could no longer be traced in the documents. Thus, 119 patients (84 men, 64 years, range 41-85) were included in the evaluation (145 lesions). Major adverse clinical events (death, myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG)) and the presence of angina were evaluated at follow-up. Furthermore a cost-effectiveness analysis was performed.Results. In 93 patients (76%) the FFR value was ≥0.75. Seventy of these 93 patients (76%) were treated with medication alone or underwent PCI for a different lesion (medical treatment group). Average duration of follow-up of all 119 patients was 22 months (range 4 days to 30 months). In the medical treatment group seven patients (10%) experienced a major adverse clinical event related to the FFR-evaluated lesion during follow-up. In this study population, the use of FFR measurement is cost-reducing provided that at least 65% of the patients in the medical treatment group has had a PCI with stent implantation when the use of FFR measurement is impossible. In this case, the decision to use PCI with stent implantation is purely based on the angiogram. Conclusions. In patients with a coronary stenosis based on visual assessment and an FFR of ≥0.75 deferral of PCI or CABG is safe in daily clinical practice and saves money. (Neth Heart J 2010;18:402-7.).

The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study.

The purpose of this study was to investigate the cardioprotective effect of the semisynthetic flavonoid 7-monohydroxyethylrutoside (monoHER) on doxorubicin (DOX)-induced cardiotoxicity in a phase II study in patients with metastatic cancer. Eight patients with metastatic cancer were treated with DOX preceded by a 10 min i.v. infusion of 1500 mg m(-2) monoHER. Five patients were examined by endomyocardial biopsy after reaching a cumulative dose of 300 mg m(-2). Histopathological changes in the cardiomyocytes (Billingham score) were compared with those described in literature for patients treated with DOX only. The mean biopsy score of the patients was higher (2.7) than the mean score (1.4) of historical data of patients who received similar cumulative doses of DOX. Although there is a considerable variability in few investigated patients, it was indicative that monoHER enhanced DOX-induced cardiotoxicity. However, the antitumour activity of DOX seemed better than expected: three of the four patients with metastatic soft-tissue sarcoma had a partial remission and the fourth patient stable disease. It is likely that the relatively high dose of monoHER is responsible for the lack of cardioprotection and for the high response rate in patients with soft-tissue sarcoma possibly by depleting the glutathione defense system in both heart and tumour.

Comparative effects of pacing-induced and balloon coronary occlusion ischemia on left ventricular diastolic function in man.

BACKGROUND: Effects of pacing-induced and coronary occlusion myocardial ischemia on left ventricular (LV) function have been compared only in anesthetized dogs. Diastolic properties of the same LV anterior wall segment were therefore compared in 12 patients with single-vessel proximal left anterior descending coronary artery stenosis at rest, immediately after 7 +/- 1.2 minutes of pacing, and at the end of a 1-minute balloon occlusion of coronary angioplasty (CO). METHODS AND RESULTS: Shifts of the diastolic LV pressure-length relation, derived from simultaneous tip-micromanometer LV pressure recordings and digital subtraction LV angiograms, were used as an index of regional diastolic LV distensibility of the anterior wall segment. Immediately after pacing, LV end-diastolic pressure rose from 13.5 +/- 3.5 to 23.8 +/- 7.0 mm Hg (p less than 0.01 versus at rest) without a significant change of the LV end-diastolic volume index (83.1 +/- 18.9 versus 88.4 +/- 16.5 ml/m2), percentage systolic shortening (%SS) of the ischemic segment fell from 40.1 +/- 10.6% to 25.2 +/- 8.6% (p less than 0.01), and the diastolic LV pressure-radial length (P-RL) plot of the ischemic segment was shifted upward by 7.1 +/- 5.0 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. At the end of CO, LV end-diastolic pressure rose to 20.8 +/- 7.8 mm Hg (p less than 0.01 versus at rest) and the LV end-diastolic volume index rose to 95.6 +/- 16.3 ml/m2 (p less than 0.05 versus at rest, p less than 0.05 versus after pacing). Ejection fraction and %SS of the ischemic segment fell respectively from 76.6 +/- 6.8% to 46.6 +/- 11.4% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing) and from 40.1 +/- 10.6% to 6.4 +/- 8.6% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing). The diastolic LV P-RL plot of the ischemic segment was shifted upward by 3.1 +/- 2.3 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. This upward shift at the end of CO was significantly smaller (p less than 0.05) than that immediately after pacing. At the end of CO, a correlation (p less than 0.03) was observed for the ischemic segment between %SS and upward shift of the diastolic LV P-RL plot. CONCLUSIONS: The upward shift of the diastolic LV P-RL plot, which was used as an index of decreased regional diastolic LV distensibility, was larger immediately after pacing than at the end of CO. Persistent systolic shortening of ischemic myocardium seems to be a prerequisite for a decrease in diastolic distensibility of the ischemic segment because of the higher %SS of the ischemic segment immediately after pacing, and because of the correlation at the end of CO between the upward shift of the diastolic LV P-RL plot and %SS of the ischemic segment.

Comparative effects of ischemia and hypoxemia on left ventricular systolic and diastolic function in humans.

BACKGROUND: During the initial phase of an ischemic insult, left ventricular (LV) performance depends on the complex interaction between oxygen deprivation, vascular turgor, and accumulation of metabolites. In experimental preparations, low-flow ischemia decreases systolic shortening and increases diastolic LV distensibility, whereas pacing-induced ischemia or hypoxic perfusion produces smaller decreases in systolic shortening but decreases LV diastolic distensibility. The purpose of this study was to investigate the different effects of low-flow ischemia, pacing-induced ischemia, and hypoxemic perfusion on LV performance in humans. METHODS AND RESULTS: In 20 patients with a significant stenosis in the left anterior descending coronary artery, micromanometer-tip LV pressure recordings (n = 20), LV angiography (n = 18), and coronary sinus blood sampling (n = 11) were obtained at rest and during the following conditions: pacing-induced ischemia (PI) (n = 11), low-flow ischemia of balloon coronary occlusion (CO) (n = 20), and hypoxemia induced by balloon coronary occlusion with hypoxemic perfusion distal to the occlusion (CO+P) (n = 11). LV stroke work index fell from 75 +/- 17 g.m at rest to 43 +/- 14 g.m at the end of CO (n = 18; P < .001). In addition, LV stroke work index was lower at the end of CO than during PI (50 +/- 11 vs 77 +/- 15 g.m; n = 11; P < .002) and was lower at the end of CO than at the end of CO+P (35 +/- 7 vs 46 +/- 9 g.m; n = 9; P < .02). LV end-diastolic pressure rose from 16 +/- 5 mm Hg at rest to 23 +/- 6 mm Hg at the end of CO (n = 20; P < .001). However, LV end-diastolic pressure was lower at the end of CO than during PI (20 +/- 5 vs 30 +/- 5 mm Hg; n = 11; P < .002) and was lower at the end of CO than at the end of CO+P (26 +/- 5 vs 34 +/- 7 mm Hg; n = 11; P < .01). LV end-diastolic volume index increased from 75 +/- 14 mL/m2 at rest to 79 +/- 15 mL/m2 at the end of CO (n = 18; P < .05). Left ventricular end-diastolic volume index increased to values similar to those for CO during PI (79 +/- 13 mL/m2; n = 11; P = NS) and at the end of CO+P (78 +/- 14 mL/m2; n = 9; P = NS). Higher values of LV end-diastolic pressure and unchanged values of LV end-diastolic volume index for PI and CO+P, compared with CO, suggested a lower end-diastolic LV distensibility during PI and during hypoxemia, as compared with low-flow ischemia. Upward shifts of individual diastolic LV pressure-volume curves during PI (9 of 11 patients) and at the end of CO+P (7 of 9 patients), compared with CO, were also consistent with lower LV diastolic distensibility during pacing-induced ischemia and during hypoxemia, compared with low-flow ischemia. Coronary sinus lactate, H+, and K+ levels increased after balloon deflation (CO and CO+P) and during pacing (PI). CONCLUSIONS: Thus, during low-flow ischemia, LV systolic performance was lower and LV diastolic distensibility larger than during pacing-induced ischemia or hypoxemia. The variable response of the human myocardium to different types of ischemia was probably related to the degree of vascular turgor and accumulation of tissue metabolites.

Deficient acceleration of left ventricular relaxation during exercise after heart transplantation.

BACKGROUND: The exercise-induced rise in left ventricular filling pressures after cardiac transplantation is considered to be the result of a blunted heart rate response, of elevated venous return, and of unfavorable passive late-diastolic properties of the cardiac allograft. In contrast to passive late-diastolic left ventricular properties, the effect of left ventricular relaxation on the exercise-induced rise in left ventricular filling pressures of the cardiac allograft has not yet been studied. In the present study, the response of left ventricular relaxation to exercise was investigated in transplant recipients and compared with left ventricular relaxation observed in normal control subjects exercised to the same heart rate. Moreover, the response of left ventricular relaxation of the cardiac allograft to beta-adrenoreceptor stimulation, to reduced left ventricular afterload, and to increased myocardial activator calcium was investigated by infusion of dobutamine and of nitroprusside and by postextrasystolic potentiation. METHODS AND RESULTS: Twenty-seven transplant recipients were studied 1 year (n = 17), 2 years (n = 7), 3 years (n = 2), and 4 years (n = 1) after transplantation. All patients were free of rejection and of significant graft atherosclerosis at the time of study. Tip-micromanometer left ventricular pressure recordings and cardiac hemodynamics were obtained at rest, during supine bicycle exercise stress testing (n = 27), during dobutamine infusion at a heart rate matching the heart rate at peak exercise (n = 8), during nitroprusside infusion (n = 9), and after postextrasystolic potentiation (n = 10). Tip-micromanometer left ventricular pressure recordings were also obtained in a normal control group (n = 9) at rest and during supine bicycle exercise stress testing to a heart rate, which matched the heart rate of the transplant recipient group at peak exercise. Left ventricular relaxation rate was measured by calculation of a time constant of left ventricular pressure decay (T) derived from an exponential curve fit to the digitized tip-micromanometer left ventricular pressure signal. In the transplant recipients, exercise abbreviated T from 43 +/- 6 to 40 +/- 8 msec (p less than 0.01) and caused a rise of left ventricular minimum diastolic pressure (LVMDP) from 5 +/- 2 to 9 +/- 6 mm Hg (p less than 0.001). In normal control subjects, exercise induced a 2.5 times larger abbreviation of T (from 42 +/- 7 to 34 +/- 6 msec; p less than 0.001) and a small drop in LVMDP from 5 +/- 2 to 4 +/- 3 mm Hg (p less than 0.05). In the transplant recipients, the change in T (delta T) from rest to exercise was variable ranging from an abbreviation, as observed in normal controls, to a prolongation and was significantly correlated with the change in RR interval (delta RR) and the change in left ventricular end-diastolic pressure (delta LVEDP) (delta T = 0.068 delta RR + 0.58 delta LVEDP-2.2; r = 0.76; p less than 0.001). In a first subset of transplant recipients (n = 8), dobutamine infusion resulted in a heart rate equal to the heart rate at peak exercise, a left ventricular end-diastolic pressure (8 +/- 7 mm Hg) lower than at peak exercise (22 +/- 6 mm Hg; p less than 0.05) and a T value (32 +/- 9 msec), which was shorter than both resting value (44 +/- 5 msec; p less than 0.005) and value observed at peak exercise (40 +/- 8 msec; p less than 0.01). In a second subset of transplant recipients (n = 9), nitroprusside infusion and postextrasystolic potentiation resulted in a significant prolongation of T from 41 +/- 7 to 56 +/- 10 msec (p less than 0.05) and a characteristic negative dP/dt upstroke pattern with downward convexity as previously observed in left ventricular hypertrophy. CONCLUSIONS: Exercise after cardiac transplantation resulted in a smaller acceleration of left ventricular relaxation than in a normal control group exercised to the same heart rate...

LAD-right ventricular fistula complicating PTCA: another case.

Coronary perforation caused by percutaneous transluminal coronary angioplasty (PTCA) occurs rarely and most often leads to communication to the pericardial space. We report a case where PTCA caused a coronary artery rupture and fistulization to the right ventricular outflow tract.

Prediction of pulmonary capillary wedge pressure and assessment of stroke volume by noninvasive impedance cardiography.

Early recognition of heart failure is important because early treatment reduces mortality and hospitalization rates. In screening for this disease, there is a need for a simple, safe, and cost-effective method to obtain cardiovascular variables. Therefore we developed a noninvasive impedance cardiographic method to predict the pulmonary capillary wedge pressure (PCWP) from the impedance cardiogram. The impedance cardiographic technique, though, was originally designed for stroke volume (SV) determination. The objectives of this study were to validate both variables by comparison with the paired, invasively obtained equivalents. PCWP, measured with a pulmonary artery catheter, was related to the O/C ratio from the impedance cardiogram. The O/C ratio was calculated as the amplitude of the impedance cardiogram during diastole (O) divided by the maximum height during systole (C). Stroke volume was also calculated from the impedance cardiogram according to the equation of Kubicek (SVIC) and compared with thermodilution (SVTD). Data analysis was performed in 24 stable patients who underwent diagnostic heart catheterization. Linear regression analysis showed that the O/C ratio was strongly related to the invasively measured PCWP over a range of 3 to 30 mm Hg (r = 0.92, standard error of the estimate, 3.2 mm Hg). Between SVIC and SVTD a moderate correlation was established (r = 0.69), but after exclusion of the data from patients with an aortic valve disorder (n = 5), the correlation increased considerably (r = 0.87). No significant differences between SVIC and SVTD were found (mean difference +/- 2 SD = 1.8 +/- 28.8 ml). These preliminary observations suggest that impedance cardiography can predict PCWP and measure SV over a wide range of clinically relevant values. The combined measurement of SV and PCWP by impedance cardiography might be a clinical useful tool in screening for heart failure.