Ticagrelor and preconditioning in patients with stable coronary artery disease (TAPER-S): a randomized pilot clinical trial.

BACKGROUND: Ticagrelor is a reversibly binding, direct-acting, oral, P2Y12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction. METHODS: To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart. DISCUSSION: Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes. TRIAL REGISTRATION: EudraCT No. 2016-004746-28. No. NCT02701140.  TRIAL STATUS: Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019. TRIAL SPONSOR: Fondazione Policlinico Universitario A. Gemelli - Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.

Impact of bridging with perioperative low-molecular-weight heparin on cardiac and bleeding outcomes of stented patients undergoing non-cardiac surgery.

When patients with coronary stents undergo non-cardiac surgery, bridging therapy with low-molecular-weight heparin (LMWH) is not infrequent in clinical practice. However, the efficacy and safety of this approach is poorly understood. This was a retrospective analysis of patients with coronary stent(s) on any antiplatelet therapy undergoing non-cardiac surgery between March 2003 and February 2012. The primary efficacy endpoint was the 30-day incidence of major adverse cardiac or cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction, acute coronary syndrome leading to hospitalisation, or stroke. The primary safety endpoint was the 30-day composite of Bleeding Academic Research Consortium (BARC) bleedings ≥ 2. Among 515 patients qualifying for the analysis, LMWH bridging was used in 251 (49 %). At 30 days, MACCE occurred more frequently in patients who received LMWH (7.2 % vs 1.1 %, p=0.001), driven by a higher rate of myocardial infarction (4.8 % vs 0 %, p< 0.001). This finding was consistent across several instances of statistical adjustment and after the propensity matching of 179 pairs. Patients bridged with LMWH also experienced a significantly higher risk of BARC bleedings ≥ 2 (21.9 % vs 11.7 %, p=0.002) compared to those who were not, which remained significant across different methods of statistical adjustment and propensity matching. In conclusion, LMWH bridging in patients with coronary stents undergoing surgery is a common and possibly harmful practice, resulting in worse ischaemic outcomes at 30 days, and a significant risk of bleeding.

Bivalirudin use in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Insights from the prospective, multi-centre EUROVISION registry.

BACKGROUND: The effectiveness of bivalirudin in patients undergoing percutaneous coronary intervention for acute myocardial infarction has been tested in clinical trials, but its use in a real-world scenario has never been reported. METHODS: From the total number of patients enrolled in the EUROVISION registry, 678 subjects affected by ST-elevation myocardial infarction were selected and included in the analysis. Posology and usage patterns of bivalirudin, as evaluated by dose and time of drug bolus and infusion administered, were evaluated. The 30-day outcome has been assessed by efficacy and safety endpoints. RESULTS: All patients received an initial intravenous bolus of bivalirudin (0.70±0.25 mg/kg) followed by an infusion (1.58±0.47 mg/kg/h; duration: 60 [30, 107] min) in 99.3% of cases. An additional bolus (0.49±0.06 mg/kg) was administered in 9.3% of patients. Bivalirudin infusion was prolonged after procedure in 62.2%. Death occurred in 2.1% of patients, non-fatal myocardial reinfarction in 0.3%, unplanned revascularization in 0.6% and non-fatal stroke in 0.4%. Acute stent thrombosis was not observed. Major bleeding occurred in 1.5% of patients. CONCLUSIONS: Bivalirudin usage in the setting of primary PCI provided excellent results in terms of 30-day outcome even in a real-world population.

Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty.

AIM: To investigate the effect of abciximab on microvascular integrity and left ventricular (LV) functional recovery in patients with acute myocardial infarction (MI) treated by primary coronary angioplasty (PTCA). METHODS AND RESULTS: Thirty-one patients (27 males; age 39-76 years) with first, acute MI (<6 h after onset) were randomized to receive either abciximab+primary PTCA (n=17) or primary PTCA alone (n=14). Baseline characteristics of the two groups were similar. Myocardial reperfusion was studied shortly after PTCA by corrected TIMI frame count (cTFC) and intracoronary myocardial contrast echocardiography (MCE), after 48 h by intravenous MCE using intermittent, harmonic power Doppler, and after 1 month by intravenous MCE and 99 mTc-tetrofosmin SPECT. The patients treated with abciximab showed a shorter cTFC (23+/-4 vs 30+/-9 frames; P<0.05), a more preserved microvascular integrity shortly after PTCA (77% vs 55%; P<0.01), after 48 h (86% vs 50%; P<0.005) and at 1-month follow-up (86% vs 54% by MCE, P<0.001, and 68% vs 60% by SPECT, P<0.005) than patients treated with PTCA alone. Abciximab patients also showed a better recovery of LV function, as demonstrated by greater reduction in wall motion score index (1.4+/-0.3 vs 1.5+/-0.2; P<0.05) and increase in LV ejection fraction (53+/-7% vs 48+/-5%; P<0.001). CONCLUSIONS: Abciximab improves microvascular perfusion and LV functional recovery in primary PTCA.

Acute-phase reactants in acute myocardial infarction: impact on 5-year prognosis.

BACKGROUND: Acute-phase reactants have recently been shown to have a short-term and possibly long-term prognostic value in acute coronary syndromes. The aim of the present study was to retrospectively verify whether serum levels of inflammation markers can predict the occurrence of early and late cardiac events after myocardial infarction. METHODS: We reevaluated 58 consecutive patients (43 men and 15 women, mean age 66 +/- 12 years) admitted to our Center during 1993 with a first myocardial infarction. Patients with non-cardiac causes of inflammation were excluded, as well as patients with a left ventricular ejection fraction <40%. From the first blood sample obtained at admission, we evaluated C-reactive protein (CRP) and alpha1-acid glycoprotein (alpha1-AGP) serum levels, the erythrocyte sedimentation rate (ESR), fibrinogen levels, and the white blood cell (WBC) count. We also evaluated the highest level of serum cardiac markers. Follow-up data were collected for 55 patients in June 1999. RESULTS: Five in-hospital and 13 delayed cardiac deaths occurred. The mean follow-up of current survivors was 5.9 +/- 0.4 years. Patients in whom cardiac death occurred had significantly higher CRP (7.4 +/- 4.1 vs 3.0 +/- 2.4 mg/dl, p < 0.001) and alpha1-AGP levels (160 +/- 38 vs 113 +/- 24 mg/dl, p < 0.001), ESR (63 +/- 30 vs 37 +/- 25 mm/hour, p < 0.001), and WBC count (13,727 +/- 3,853 vs 10,936 +/- 3,358/mm3, p = 0.004). At multivariate analysis, higher alpha1-AGP (p < 0.001) and CRP serum levels (p = 0.02) were independent predictors of cardiac death. Patients in whom cardiac events occurred during follow-up showed higher CRP (5.7 +/- 3.7 vs 1.6 +/- 1.5 mg/dl, p < 0.001) and alpha1-AGP levels (140 +/- 36 vs 101 +/- 23 mg/dl, p < 0.001) and ESR (50 +/- 30 vs 34 +/- 26 mm/hour, p = 0.06). Higher alpha1-AGP (p < 0.001) and CRP serum levels (p = 0.03) were independent predictors of the occurrence of cardiac events. CONCLUSIONS: The present study shows that CRP and alpha1-AGP have an independent prognostic value in patients presenting with a first, uncomplicated myocardial infarction. Assays of these markers may help to better stratify patients hospitalized for acute coronary syndromes.

Assessment of coronary vasomotor function: old and new tools.

Atherosclerosis has an impact on the vasomotor reaction of coronary segments to iodinated non-ionic contrast agents. Angiographically normal coronary segments show divergent vasomotor reactions to iodixanol or iopromide according to the presence of, and distance from, a coronary atherosclerotic lesion. The mechanism responsible for the above-mentioned vasomotor effect does not seem to involve flow-mediated vasodilation or endothelial nitric oxide synthesis. On the other hand, a cyclooxygenase product may be, at least in part, responsible for the vasodilating effect of non-ionic agents on epicardial coronary arteries. These findings have potential clinical implications that are herein discussed.

Usefulness of carotid intima-media thickness measurement and peripheral B-mode ultrasound scan in the clinical screening of patients with coronary artery disease.

Previous observational studies have shown a relationship between carotid intima-media thickness (IMT) and coronary artery disease (CAD). In this study the authors evaluated the accuracy of the common carotid IMT measurement in predicting the presence and severity of CAD and the additional information offered by the detection of carotid, iliac, and lower limb plaques. One hundred and fifty consecutive patients were subjected to coronary angiography and carotid, iliac, and lower limb ultrasound scan. The mean value of six IMT measurements of the far wall of the common carotid artery was calculated in each patient. The mean IMT was significantly correlated to the number of stenosed coronary vessels (r = 0.43, p<0.001), although the positive and negative predictive value of mean IMT in identifying patients with CAD was low (81% and 46%, respectively). The combined information offered by IMT measurements and peripheral (carotid, iliac, and lower limb) plaque detection was then used to obtain the best multivariate regression model able to predict CAD status. The multivariate model showed a highly significant multiple correlation coefficient (r = 0.60, p<0.0001) and a sharp improvement in the negative predictive value (92%) with respect to the univariable model. B-mode ultrasound scan including common carotid IMT measurement and peripheral plaque detection may be of clinical value in the screening of patients with CAD.

The impact of coronary artery disease on the coronary vasomotor response to nonionic contrast media.

BACKGROUND: Coronary artery disease (CAD) alters the vasomotor response to a variety of pharmacological agents. We tested the hypothesis that CAD also has an impact on the coronary vasomotor response to radiologic contrast media. METHODS AND RESULTS: We performed quantitative coronary angiography in 42 patients without angiographic evidence of CAD and 38 patients with CAD in the left coronary artery. Angiographically smooth coronary segments (n=235) were analyzed for changes on luminal diameters and coronary venous oxygen saturation in response to 3 media: the nonionic dimer iodixanol, the nonionic monomer iopromide, and the ionic agent ioxaglate. In subjects without CAD, we assessed the effects of intracoronary administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine and of the cyclooxygenase inhibitor indomethacin on such changes. Iodixanol induced coronary vasodilation in subjects without CAD (8.8+/-8.6%, P<0.001). Patients with CAD exhibited no significant diameter changes in segments >/=20 mm apart from a stenosis (4.7+/-9.4%, P=NS) and significant constriction in segments <20 mm from a stenosis (-3.8+/-4.6%, P<0. 05). Similar results were obtained with iopromide, but no changes were found with ioxaglate. All contrast media induced transient (<35 seconds) increases in coronary venous oxygen saturation in all subjects. Indomethacin, but not N(G)-monomethyl-L-arginine, blunted the vasodilating effect of iodixanol and iopromide (by 80% and 76%, respectively; P<0.001). CONCLUSIONS: Nonionic contrast media induce a vasodilatory response in normal vessels not by a mechanism involving increased flow or endothelial nitric oxide synthesis, but rather by depending on preserved vascular cyclooxygenase activity. CAD changes normal epicardial vasodilatory response into vasoconstriction.

Endothelin-1 release from atherosclerotic plaque after percutaneous transluminal coronary angioplasty in stable angina pectoris and single-vessel coronary artery disease.

To assess the effects of percutaneous transluminal coronary angioplasty on endothelin-1 (ET-1) release, we assessed ET-1 concentrations at different sites of the coronary circulation in patients submitted to elective procedures. ET-1 levels immediately downstream from the plaque and ET-1 aortocoronary gradient increased significantly after the procedure, which was related to mechanical wall stress in patients only receiving balloons, but not in those undergoing stent percutaneous transluminal coronary angioplasty. No changes were found in the coronary sinus; these results suggest ET-1 release from the plaque rather than an ischemia/reperfusion-related production from the distal myocardium.

[Effects on vasomotor tone and hemostatic function of radiologic contrast media used during invasive cardiological procedures]. / Effetti sul tono vasomotore e sulla funzione emostatica dei mezzi di contrasto radiologici utilizzati in corso di procedure cardiologiche invasive.

There are several types of radiologic contrast media which can be used in invasive cardiology: 1) ionic media with high osmolality (2000 mOsm/kg, about 6 times that of plasma), the prototype of which is diatrizoate; 2) ionic media with low osmolality (600-900 mOsm/kg), the prototype of which is ioxaglate; 3) non-ionic monomeric, low-osmolality media, such as iopromide, iopamidol and iohexol; and 4) non-ionic dimeric media, iso-osmolal compared to plasma (290-300 mOsm/kg), among which the most used is iodixanol. Non-ionic media--by far the most expensive--have a generally better tolerability profile for the patient, since they clearly induce a less gastro-intestinal, renal, hemodynamic, electrophysiological and pseudo-allergic side effects. They interfere much less with the physiology of vascular and circulating blood cells, and have lesser negative interference on the hemostatic function. Whether these lesser anti-hemostatic properties become a possible downside in situations at high thrombotic risk, such as in some interventional procedures, has been so far the object of isolated reports, usually with limited numbers of patients, and is presently being verified in adequate clinical trials. Radiologic contrast media also have disparate vasoactive properties on epicardial and myocardial resistance vessels. The knowledge and awareness of such effects is of potential importance for the performance of studies requiring the accurate quantitative evaluation of coronary diameters or of myocardial blood flow.

A Study on Vascular Retinal Alterations in Patients with Coronary Artery Disease.

The paper describes the study carried out on a sample of 27 coronary artery disease patients, aiming to determine a correlation between coronary artery disease and anomalies in the retinal circulation. Patients underwent selective coronary arteriography and fundus fluorescein angiography that allowed us to investigate the dye dynamics and to detect abnormalities of time evolution, vessel walls, and flux. During the fluorescein angiography we measured time events as the choroidal flush (ta) the start of the laminar phase (tb), and the end of the laminar phase (tc) and we took pictures that were digitally processed in order to compute the ROI1/ROI2 value, assumed as a numerical index of ischemia of the optic disc. In the examined sample we found ta = 61 +/- 109, tb = 65 +/- 107, tc = 159 +/- 155, and ROI1/ROI2 = 0.968 +/- 0.300. Normal ranges for these parameters were determined by the fundus fluorescein angiography of a control group of 10 patients, unaffected by coronary artery disease and ischemic pathology of the retinal network; we found ta = 12 +/- 4, tb = 16 +/- 8.5, tc = 44 +/- 9.3, and ROI1/ROI2 = 0.735 +/- 0.086. Eighty-five percent of coronaropatic patients showed ischemia of the optic disc, 89% anomalies of the epi-peripapillar network, 70% anomalies of the papillo-macular network, and 89% evidence of at least two findings of ischemia; 85% of patients showed a value of ROI1/ROI2 out of the normal range. The unpaired Student's t-test between the coronaropatic and the control group does not show significant differences between ta and tb; on the contrary, those with coronary disease and the control group were statistically different for tc (p

Coronary collateral circulation behaviour and myocardial viability in chronic total occlusion treated with coronary angioplasty.

AIMS: We explored the role of microcirculation integrity following the chronic occlusion of an infarct-related artery to assess the behaviour of collateral circulation during and after reperfusion by coronary angioplasty METHODS AND RESULTS: Eighteen patients with a proximally occluded left anterior descending artery and firm evidence of intercoronary collateral circulation were studied with selective coronary angiography and selective intracoronary myocardial contrast echocardiography, before coronary angioplasty, and at 5 and 15 min and 12 h later. Myocardial enhancement during myocardial contrast echocardiography was evaluated with a semiquantitative score (0-3), which was correlated to basal and 6 months' regional left ventricular wall motion results. 16/18 procedures were successfully performed; four patients with an inadequate acoustic window were excluded. Restenosis was evident at the 6 months' follow-up in two patients. Basal myocardial contrast echocardiography indicated that 81/192 segments from the left anterior descending coronary artery and 90/192 from the right coronary artery were perfused; no perfusion was observed in 21 segments either before or after coronary angioplasty. After coronary angioplasty, the angiographic intercoronary collateral circulation immediately disappeared, and myocardial contrast echocardiography revealed that there was a progressive reduction of segments perfused by the right coronary artery and an increase in segments perfused by the left anterior descending coronary artery. Regional left ventricular wall motion analysis demonstrated that there was abnormal motion in 51/192 segments. There was no improvement in segments with score 0 and abnormal motion after 6 months (100% sensitivity), but 16/17 segments with score 3 did show an improvement (98% specificity). The predictive value of intermediate scores (1-2) in detecting long-term improvement, was only 43%. CONCLUSION: These data show that the adaptive mechanism observed in the behaviour of epicardial and microvascular circulation after reperfusion of a chronic occluded infarct-related artery can vary. In addition, this study clearly shows that microvascular integrity detected by myocardial contrast echocardiography can provide myocardial viability.

Altered autonomic cardiac control in hypertrophic cardiomyopathy. Role of outflow tract obstruction and myocardial hypertrophy.

AIM: The goal of this study was to investigate the role of left ventricular outflow tract obstruction and myocardial hypertrophy on autonomic cardiac function in patients with hypertrophic cardiomyopathy. METHODS AND RESULTS: The sympatho-vagal function was evaluated by spectral analysis of heart rate variability in 28 patients with hypertrophic obstructive cardiomyopathy, 22 patients with hypertrophic non-obstructive cardiomyopathy, 12 with systemic hypertension and left ventricular hypertrophy and 28 healthy subjects. Left ventricular out-flow tract pressure gradient in patients with hypertrophic cardiomyopathy was evaluated by echo-Doppler methods and the quantitative assessment of left ventricular hypertrophy was based on an echocardiographic index. At rest, patients with hypertrophic non-obstructive cardiomyopathy showed normal spectral patterns, while in patients with hypertrophic obstructive cardiomyopathy and in patients with systemic hypertension we observed, respectively, a significant reduction and increase in the low frequency component relative to the control (P < 0.05). During tilt, the physiological increases in the low frequency component and in the low to high frequency ratio were markedly blunted, or even reverted, only in patients with hypertrophic obstructive cardiomyopathy. In these patients, the heart rate increase during tilt was delayed in comparison to the other groups. Finally, in the hypertrophic obstructive cardiomyopathy group, the impairment of sympathetic activation (lack of increase in the low frequency component during tilt) was significantly correlated to the echocardiographic index of left ventricular hypertrophy (r = -0.800, P < 0.001) rather than to the left ventricular outflow tract pressure gradient (r = 0.295, P: ns). CONCLUSION: Among patients with hypertrophic cardiomyopathy, only those with outflow tract obstruction show spectral signs of altered autonomic cardiac control. Within this group, the autonomic dysfunction appears to be correlated to myocardial hypertrophy rather than to left ventricular outflow tract obstruction.

Alteration of cardiac function in patients with temporal lobe epilepsy: different roles of EEG-ECG monitoring and spectral analysis of RR variability.

PURPOSE: Because several reports have described the relation between epilepsy and cardiac arrhythmias and suggest that changes in autonomic neural control of the heart could be involved in the pathogenesis of sudden unexplained death in patients with epilepsy, the aim of this study was to evaluate cardiac function in patients with temporal lobe epilepsy. METHODS: Sixty-five patients with epilepsy were evaluated by simultaneous ambulatory 24-h EEG-ECG monitoring, and in 30 of these, power spectral analysis of relative-risk (RR) variability also was carried out, both in the supine position and in a passive tilt position at 60 degrees. The power spectrum of RR variability, the two major spectral components detectable at low frequency (LF) and at high frequency (HF), respectively, and the LF/HF ratio were calculated. RESULTS: By EEG-ECG monitoring, we recorded six partial seizures, and in four cases, discharges were associated with sinus tachycardia. However, interictally the occurrence of ventricular and supraventricular arrhythmias was not different from that in normal subjects. The spectral analysis of RR variability, on the other hand, demonstrated in patients with epilepsy a significant decrease in the total RR variability and in both of its components (LF and HF) in the supine position, and of the LF/HF ratio in orthostatic position. CONCLUSIONS: These findings suggest that the spectral analysis of RR variability may detect disorders of autonomic cardiac control in patients with epilepsy, even in the absence of abnormal findings during ECG monitoring. This alteration, which is more severe in cases with right EEG focus, could play a role in the pathogenesis of cardiac arrhythmias.

[Incidence of peripheral vascular complications in subjects undergoing coronary angioplasty]. / Incidenza di complicanze vascolari periferiche in soggetti sottoposti ad angioplastica coronarica.

The peripheral vascular complications following cardiac catheterization for interventional procedures are increasing. The aim of our study is to evaluate the importance of the early removal of the arterial sheath in reducing vascular complications. We examined 451 consecutive patients, submitted to percutaneous transluminal coronary angioplasty (PTCA) by femoral approach. In 229 patients (Group A), we removed the arterial sheath 12-14 hours after PTCA; in 222 patients (Group B) the arterial sheath was removed as soon as possible at the end of PTCA. In 31 Group A and 5 Group B patients we performed a coronarographic study after 12-14 hours. In total, 16 patients (11 Group A, 5 Group B) presented vascular complications. None of the risk factors that we have considered was predictive for complications, except that iliacofemoral atherosclerotic disease. In patients undergoing complex procedures we have found a greater amount of vascular complications. The coronarographic control revealed some pathologic lesion (dissection, occlusive thrombus) only in patients with clear ischemic signs or symptoms, both in Group A and B. In our opinion, an early removal of the arterial sheath reduces the incidence of vascular complications and the period of in-hospital stay.

[Spectrum analysis of heart rate variability in obstructive hypertrophic myocardiopathy. Evidence of altered autonomic function]. / Analisi spettrale della variabilità della frequenza cardiaca nella miocardiopatia ipertrofica ostruttiva. Evidenze per una alterata funzione neurovegetativa.

Altered sympathetic activity may play an important role in the pathogenesis of hypertrophic obstructive cardiomyopathy (HOCM). Spectral analysis of heart rate variability was employed to assess the sympatho-vagal function and balance in 18 patients with HOCM (11 males, 7 females, mean age 42 years, range 19-59) and in 15 healthy control subjects (9 males, 6 females, mean age 44 years, range 18-65). Electrocardiographic recordings obtained both at rest and during 60 degrees passive tilt, were digitized and analyzed by fast Fourier transform in order to obtain the power spectrum of heart rate variability. The low-frequency band (LF: 0.05-0.17 Hz) and the high-frequency band (HF: 0.18-0.34) of power spectrum were considered as indexes of sympathetic and vagal activities respectively. A semiquantitative two-dimensional echocardiographic score (SES) was used to assess the entity of myocardial hypertrophy whereas the entity of the intraventricular gradient was determined by continuous wave Doppler. Low-frequency band at rest was slightly but significantly reduced in HOCM group with respect to controls (35.2 +/- 2.0 vs 45.0 +/- 2.5 nu, respectively; p < 0.01), whereas the HF band and the LF/HF ratio were not different in the 2 groups. During tilt, control subjects showed a significant reduction of the HF band (-35%, p < 0.001), an increase in the LF band (+36%, p < 0.001) and a sharp increase in the LF/HF ratio (+105%, p < 0.001). On the contrary the baroreflex increase in the LF band and LF/HF ratio during tilt was markedly blunted, or even reverted, in patients with HOCM (-9%, NS and +5%, NS, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of verapamil, gallopamil, diltiazem and nifedipine on sarcoplasmic reticulum function in rat heart.

We investigated the effect of the calcium antagonists verapamil, gallopamil, diltiazem and nifedipine on cardiac sarcoplasmic reticulum function. In a cell-free homogenate from rat hearts, oxalate-supported Ca uptake was stimulated by verapamil, gallopamil and diltiazem at concentrations in the order of 10 nM to 100 nM, while higher concentrations were ineffective. Nifedipine was also ineffective. Peak stimulation of Ca uptake averaged 15-20% of control. Ca uptake is the difference between active Ca transport by Ca-ATPase and passive efflux through sarcoplasmic reticulum channels. In the presence of 300 microM ryanodine, which blocks sarcoplasmic reticulum channels, Ca uptake increased by 50%, but no further stimulation was produced by the addition of any calcium antagonist, at concentrations ranging from 1 nM to 100 microM. In a fraction enriched in sarcoplasmic reticulum, no drug affected the activity of Ca-ATPase at concentrations able to stimulate Ca uptake. We conclude that low concentrations of verapamil, gallopamil and diltiazem reduce Ca efflux through the Ca channels of the sarcoplasmic reticulum. Such an action might contribute to the clinical effect of these drugs.