Epidemiology of heart failure in Germany: a retrospective database study.

BACKGROUND: Chronic heart failure (HF) is associated with significant healthcare expenditure, morbidity, and mortality. This study investigated the epidemiology of HF in Germany. METHODS: This retrospective study used anonymous healthcare claims data from the German Health Risk Institute on individuals with statutory health insurance. Patients with uninterrupted data from 1 January 2009 to 31 December 2013 or death (whichever occurred first), and ≥2 recorded HF-related diagnoses in 2011, were included. Patients with newly diagnosed HF were identified. Patients were followed up for 2 years from first diagnosis. RESULTS: Of 3,132,337 eligible patients, 123,925 (55.0% women; mean age 76.2 years) had HF: a prevalence of 3.96%. Of these, 26,368 had newly diagnosed HF: an incidence of 655/100,000 persons at risk. Incidence increased with age and was similar regardless of sex. During follow-up, there were 48,159 hospital admissions among newly diagnosed patients (1.8 hospitalizations/patient/2 years); HF accounted for 6% of these. Additionally, 20,148 patients (16.3%) overall and 5983 newly diagnosed patients (22.7%) died. Most new cases of HF were diagnosed by office-based physicians (63.2%); new cases among hospital inpatients were predominantly diagnosed by internal medicine specialists (70.7%). Overall, 94.0% received their initial prescription for HF treatment from a family practitioner. CONCLUSIONS: The high prevalence and incidence observed in this representative sample emphasize the burden of HF in Germany. Substantial hospitalization rates and mortality highlight the need for early diagnosis and appropriate treatment, and for close cooperation between physician specialties and healthcare sectors.

Treatment of chronic heart failure in Germany: a retrospective database study.

BACKGROUND: Adherence to treatment guidelines affects outcomes in patients with chronic heart failure (HF). We investigated patient pathways and treatment patterns for HF in Germany. METHODS: This retrospective study used anonymous healthcare claims data from the German Health Risk Institute on individuals with statutory health insurance. Patients with uninterrupted data from 1 January 2009 to 31 December 2013 or death (whichever occurred first), and ≥2 recorded HF-related diagnoses in 2011, were included. Patients with newly diagnosed HF were identified. Use of treatment patterns recommended by the European Society of Cardiology (2008) and German Nationale VersorgungsLeitlinien (2011) guidelines was evaluated. RESULTS: Of 123,925 patients with HF, 21.3% were newly diagnosed. Overall, 63.2% of new HF diagnoses were made in the ambulatory setting; 61.6% of these were made by family practitioners and 14.8% by cardiologists. In the ambulatory setting, family practitioners were primarily responsible for treatment; specialists in internal medicine (70.3% cardiologists) were mainly responsible for performing HF-related technical diagnostics. One-fifth (20.9%) of patients received a New York Heart Association (NYHA) classification; 45.1% of these received a guideline-based treatment pattern. Application of the recommended treatment pattern decreased with advancing disease severity (NYHA class IV: 21.1% application) and older age (≥90 years: 28.3% application). CONCLUSIONS: Family practitioners play a key role in the diagnosis and initial treatment of HF in Germany. A substantial proportion of patients do not receive guideline-recommended pharmacotherapy. These findings should be reflected in the planning of national disease management programmes.

Impact of supportive measures on drug adherence in patients with essential hypertension treated with valsartan: the randomized, open-label, parallel group study VALIDATE.

OBJECTIVE: The majority of treated hypertensive patients do not achieve target blood pressure (BP) levels of less than 140/90 mmHg. One key reason is inadequate adherence with the prescribed drug regimen. Dosing regimens are either not executed as prescribed (noncompliance) or patients stop taking the medication (nonpersistence). It has been demonstrated that adherence with angiotensin receptor antagonists such as valsartan is high due to the tolerability profile of this drug class. The present study was designed to evaluate whether drug adherence could further be improved by the use of supportive measures. DESIGN AND METHODS: Twenty-eight centers were randomized to provide pharmacological treatment with or without a set of supportive measures (e.g. structured physician-patient interaction, printed information about hypertension, reminder stickers, 24 h timer, and home BP measurement device). Two hundred and two patients with grade 1 hypertension (BP at baseline 149.8 +/- 6.2/93.9 +/- 4.4 mmHg) who were either newly diagnosed or who had not been treated for at least 1 year were included in this trial. All patients entered the 34-week treatment phase with valsartan 160 mg daily. Titration to valsartan 160 mg/hydrochlorothiazide 12.5 mg was allowed if necessary. Drug adherence was assessed by electronic monitors (Medication Event Monitoring System). RESULTS: Patients treated with a valsartan-based therapy receiving supportive measures as compared with the standard care group demonstrated an initially higher level of adherence with a maximum absolute difference of 7.8% (P = 0.041). This difference did not persist over the observation period but faded with time. In parallel, execution of the dosing regimen (compliance) was also improved in the intervention group during the early months of treatment but this effect also disappeared by the end of the observation period. In contrast, persistence in the two groups slowly but continuously separated over time. Estimated absolute difference in persistence at the end of the 34-weeks study between the two groups was 7.6% (95.9 vs. 88.3%) reflecting a 66% lower hazard of discontinuation in the intervention group (P = 0.073). BP control improved more in patients with the supportive measures. CONCLUSION: Drug adherence improved initially with the use of supportive measures. However, this effect faded with time mainly because of the short-lived improvement in the quality of execution (compliance) achieved. In contrast, a longer lasting effect of the chosen supportive measures on persistence could be demonstrated, which, however, at least under the conditions of the present study, did not translate into a persistent improvement of medication adherence.

Valsartan in combination with lisinopril versus the respective high dose monotherapies in hypertensive patients with microalbuminuria: the VALERIA trial.

OBJECTIVES: Microalbuminuria is known as an independent predictor for stroke, myocardial infarction, and death. The purpose of the VALERIA trial was a comparison of the efficacy and safety of combination therapy of valsartan and lisinopril with valsartan and lisinopril high-dose monotherapy in patients with hypertension and microalbuminuria. METHODS: This was a randomized, double-blind, interventional, parallel-group study. After a washout/placebo-run-in phase of 3 weeks, 133 patients were randomized to treatment (1: 1:1) with either lisinopril 40 mg, valsartan 320 mg, or a combination of valsartan/lisinopril 320/20 mg for 30 weeks. RESULTS: At baseline, the urine albumin creatinine ratio was similar for the three treatment groups (geometric means, lisinopril 9.6 mg/mmol, valsartan 9.1 mg/mmol, and valsartan/lisinopril 9.5 mg/mmol). After 30 weeks of treatment, the geometric mean urine albumin creatinine ratio had decreased in all three groups by 41, 51, and 62% to 5.7 mg/mmol (lisinopril), 4.5 mg/mmol (valsartan), and 3.6 mg/mmol (valsartan/lisinopril). The decrease for valsartan/lisinopril was statistically significantly greater compared with lisinopril [adjusted ratio 60%, confidence interval (38-94%), P = 0.029]. Normalization of microalbuminuria was greatest with valsartan and valsartan/lisinopril (lisinopril 17%, valsartan 31%, and valsartan/lisinopril 38% of patients) and was statistically significant for lisinopril in contrast with valsartan/lisinopril (P = 0.034). Differences in blood pressure reduction between the groups were not statistically significant. All treatments were safe and well tolerated. CONCLUSION: The combination of valsartan and lisinopril provided a significantly better reduction of urine albumin creatinine ratio and more than doubled the rate of patients with normalized urine albumin creatinine ratio compared with lisinopril alone. All treatments were safe and well tolerated.

Effective and safe reduction of blood pressure with the combination of amlodipine 5 mg and valsartan 160 mg in hypertensive patients not controlled by calcium channel blocker monotherapy.

INTRODUCTION: The addition of an angiotensin II receptor blocker to calcium channel blocker-based antihypertensive therapy may be associated with enhanced efficacy and reduced risk of adverse events. METHODS: This 8-week, open-label, single-arm trial evaluated the efficacy and tolerability of the combination of amlodipine and valsartan in patients not responding adequately to treatment with amlodipine or felodipine alone. Patients aged > or =18 years with moderate essential hypertension (defined as mean sitting systolic blood pressure [MSSBP] > or =160 and <180 mmHg) were treated for 4 weeks with once-daily amlodipine 5 mg or felodipine 5 mg. At week 4, patients not adequately responding were treated for an additional 4 weeks with once-daily amlodipine 5 mg plus valsartan 160 mg. Of 214 patients treated for 4 weeks with amlodipine 5 mg or felodipine 5 mg, 181 failed to achieve MSSBP <140 mmHg. These non-responders were treated for an additional 4 weeks with amlodipine 5 mg and valsartan 160 mg. RESULTS: A clinically and statistically significant additional reduction in MSSBP of 13.1 mmHg (95% confidence interval [CI]: 11.4, 14.7; P<0.0001) and a mean sitting diastolic blood pressure of 5.3 mmHg (95% CI: 4.3, 6.3; P<0.0001) were observed. Of patients treated with amlodipine 5 mg and valsartan 160 mg, 51.1% achieved target blood pressure levels (<140/90 mmHg) after 4 weeks. Adverse event rates were low in both treatment phases, and most were mild or moderate in severity. CONCLUSION: The combination of amlodipine/valsartan was effective and well tolerated.

Valsartan and retinal endothelial function in elderly hypertensive patients.

BACKGROUND: The aim of this study was to investigate the impact of short-term treatment with the angiotensin II receptor blocker (ARB) valsartan on retinal endothelial function in elderly patients with mild to moderate essential hypertension. METHODS: In an open-labeled study, 20 elderly, male patients with arterial hypertension (WHO I-II) were treated with the ARB valsartan (80-160 mg once daily) over 8 days. Central retinal artery perfusion at rest and during flicker light stimulation was measured before and after treatment using pulsed wave Doppler sonography. Retinal capillary flow was assessed with scanning laser Doppler flowmetry at rest and following systemic infusion of the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA). RESULTS: While valsartan significantly lowered blood pressure, central retinal artery perfusion at rest as well as after flicker light stimulation was similar before and after treatment. Similarly, retinal capillary flow at rest and after infusion of L-NMMA did not change with valsartan after 7 days of treatment. Subgroup analysis revealed that changes in retinal capillary flow in response to L-NMMA might be dependent on serum low-density lipoprotein (LDL) cholesterol levels of study participants. After treatment with valsartan, retinal capillary flow in response to L-NMMA decreased more in patients with low (< 3.54 mmol/l) than with high LDL-cholesterol levels (-12.6 +/- 20.2% vs 12.3 +/- 19.5%, p < 0.05). CONCLUSION: Short-term treatment with valsartan did not improve retinal endothelial function in elderly hypertensive patients.

Prognostic value of the QRS duration in patients with heart failure: a subgroup analysis from 24 centers of Val-HeFT.

BACKGROUND: This study investigated whether QRS duration (QRS D) is a prognostic indicator in patients with heart failure (New York Heart Association [NYHA] classes II-IV). METHODS AND RESULTS: This subgroup analysis included 248 patients with heart failure recruited in the German centers of the Valsartan Heart Failure Trial (Val-HeFT). Mean age was 60 years, mean NYHA class was 2.3, and mean left ventricular ejection fraction (EF) was 27.9%. Electrocardiograms were recorded and analyzed at the beginning of the study, at 2 weeks, 4 months, 1 year, and 2 years. The mean observation period for mortality was 25 months. Patients > or = 65 years and patients with an EF <20% had a significantly longer QRS D (P = .02; P = .0005). NYHA class, etiology of heart failure, therapy with angiotensin-converting enzyme inhibitors, amiodarone or beta-blockers, implanted defibrillator, and atrial fibrillation had no significant influence on QRS D. Total mortality was 9%: 14 patients died suddenly, 7 from heart failure, 2 from noncardiac causes. Kaplan-Meier plots show significantly different survival rates for patients with QRS D <120 ms, QRS D 120-159 ms, or QRS D > or = 160 ms (P = .0085). Multivariate analysis showed that QRS D was the only independent risk factor for all-cause mortality (P = .008). NYHA class, EF, atrial fibrillation, age, and gender failed to qualify as independent prognostic factors. CONCLUSION: QRS duration in the surface electrocardiogram is an easily obtainable parameter with a significant prognostic impact in patients with congestive heart failure and a reduced EF. In this German subgroup of Val-HeFT patients, it was an independent predictor of all-cause mortality.

The role of nitric oxide in the regulation of glomerular haemodynamics in humans.

BACKGROUND: According to experimental data, the afferent glomerular arteriole is particularly under control of nitric oxide (NO). By use of pharmacological manoeuvres, we examined whether this finding holds true in the human renal circulation in vivo. METHODS: Seventy-seven volunteers (aged 50+/-9 years) with mild to moderate essential hypertension (n = 57) or arterial normotension (n = 20) were examined. Basal NO activity in the renal circulation was assessed by the change of renal plasma flow (RPF) through systemic infusion of the NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg). Hypertensive patients were treated over 8 weeks with either the calcium-channel blocker amlodipine or the AT(1)-receptor blocker valsartan, primarily dilating the afferent and efferent arteriole, respectively. Subsequently, renal haemodynamics and NO activity in the renal circulation were determined again. RESULTS: L-NMMA reduced RPF in normotensive (by 57+/-70 ml/min/1.73 m(2); P<0.01) and hypertensive subjects (by 46+/-56 ml/min/1.73 m(2); P<0.001) with no significant difference between the two groups. The decrease of RPF through L-NMMA was closely related with the glomerular filtration rate (GFR; r = 0.39, P<0.001). Administration of amlodipine increased GFR by 7.1+/-12.1 ml/min/1.73 m(2); (P<0.01) and in parallel reduced the response of RPF to L-NMMA to 19+/-48 ml/min/1.73 m(2); (P<0.05). In contrast, valsartan maintained GFR and left the response of RPF to L-NMMA unchanged. CONCLUSIONS: NO plays an important role in the regulation of human glomerular haemodynamics, probably with a greater contribution to afferent than to efferent arteriolar tone in man.

Ca2+-dependent modulation of single human cardiac L-type calcium channels by the calcineurin inhibitor cyclosporine.

OBJECTIVE: Activity of single L-type calcium channels (LTCC) is enhanced in human failing myocardium (Circulation 98 (1998) 969.), most likely due to impaired dephosphorylation. Protein phosphatase 2B (calcineurin) has recently been shown to be involved in heart failure pathophysiology. We now focus on the regulation of single LTCC by calcineurin that were prevented by Ca(2+)-free experimental conditions in our previous study. METHODS: Single LTCC currents were recorded in myocytes from human atrium and ventricle. Charge carriers were 70 mM Ba(2+), or a mixture of 30 mM Ca(2+) and 60 mM Ba(2+) to facilitate Ca(2+) permeation through recorded channels. The calcineurin inhibitor cyclosporine (10 microM) was used to reveal a putative role for calcineurin in regulation of LTCC. RESULTS: A mixture of Ca(2+) and Ba(2+) as charge carriers allowed for Ca(2+) permeation through recombinant human embryonic kidney cells and native (atrial and ventricular) human cardiac LTCC. With only Ba(2+) as the charge carrier, activities of both ventricular and atrial LTCC were strongly decreased by cyclosporine. In contrast, channel activity remained constant when Ca(2+) permeation was provided. In the presence of thapsigargin and (S)-BayK 8644, cyclosporine here even increased channel activity. CONCLUSIONS: We propose a dual cyclosporine effect on human cardiac LTCC. A non-specific inhibitory effect prevails with Ba(2+) permeation but can be compensated or overcome by a specific Ca(2+)-dependent stimulation with Ca(2+) permeation. More complete restoration of physiological Ca(2+) movements (e.g., Ca(2+) release from sarcoplasmic reticulum) will help to define even more precisely the involvement of calcineurin in regulation of human cardiac LTCC.

Efficacy and Safety of Valsartan 160mg/Hydrochlorothiazide 25mg Combination in Patients with Hypertension not Adequately Controlled by Valsartan 160mg/Hydrochlorothiazide 12.5mg.

BACKGROUND AND OBJECTIVE: Hypertension guidelines emphasise the need to treat high blood pressure (BP) early and aggressively, giving fixed-dose combinations special consideration. Hitherto, it has not been assessed in a sequential way whether hypertensive patients with inadequately controlled hypertension with an angiotensin II receptor antagonist/hydrochlorothiazide combination benefit from a dose increase of the diuretic. We investigated the efficacy and safety of valsartan 160mg/hydrochlorothiazide 25mg combination in patients with hypertension that was not adequately controlled by valsartan 160mg/hydrochlorothiazide 12.5mg. PATIENTS AND METHODS: This was a multicentre, single-group, prospective study of 646 patients with moderate hypertension (diastolic BP [DBP] 100-109mm Hg). Patients were treated for 4 weeks with valsartan 160mg/hydrochlorothiazide 12.5mg (phase 1: weeks 1-4). In case of non-response (DBP >/=90mm Hg; n = 224) patients were treated for a further 4 weeks with valsartan 160mg/hydrochlorothiazide 25mg (phase 2: weeks 5-8). The primary efficacy measure was a change in mean sitting trough DBP at study end compared with the beginning of phase 2 in the intention-to-treat (ITT) population (n = 221). RESULTS: Mean age of patients at entry was 58.6 years; 53.7% of patients were female. In phase 1, systolic BP (SBP)/DBP decreased from a baseline value of 161.9/103.3mm Hg by -16.1/-12.4mm Hg (normalisation rate 38.3%, response rate 64.5%). In phase 2, in the ITT non-responder population the additional SBP/DBP decrease was -8.4/-8.3mm Hg. Overall, the normalisation rate in all patients was 55.4% and the responder rate was 76.3%.Tolerability of both the valsartan 160mg/hydrochlorothiazide 12.5mg and the valsartan 160mg/hydrochlorothiazide 25mg combinations was very good, and the switch to the higher dose did not result in an increase in adverse events (AEs) or laboratory abnormalities. Only 16.6% of patients in phase 1 and 10.3% of patients in phase 2 experienced one or more AEs. CONCLUSION: In patients with moderate hypertension, first-line therapy with the fixed-dose valsartan/hydrochlorothiazide combination leads to high normalisation and response rates. Patients with hypertension not controlled by valsartan 160mg/ hydrochlorothiazide 12.5mg clearly benefit from dose titration to valsartan 160mg/hydrochlorothiazide 25mg with a clinically relevant additional BP response and have excellent tolerability.

Direct comparison of the effects of valsartan and amlodipine on renal hemodynamics in human essential hypertension.

BACKGROUND: To elucidate the renoprotective mechanism of AT(1)-receptor blockers, we compared the effects of the AT(1)-receptor blocker valsartan with those of the calcium channel blocker amlodipine on renal hemodynamics and microcirculation. METHODS: A total of 58 patients (50.2 +/- 9.0 years) with mild to moderate essential hypertension were included in a randomized, double-blind study to receive either valsartan (80 to 160 mg) or amlodipine (5 to 10 mg). Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured before and after 8 weeks of treatment. Glomerular hydrostatic pressure (P(Glo)) and resistances of the afferent (R(A)) and efferent (R(E)) arterioles were calculated according to the Gomez formulas. RESULTS: Blood pressure control was similar in both groups. RPF did not change with either treatment. In contrast, GFR increased with amlodipine (+8 +/- 14 mL/min; P <.01) but was preserved with valsartan. Amlodipine caused a more marked increase in the R(E)/R(A) ratio than valsartan (+0.26 +/- 0.26 v +0.13 +/- 0.24, P <.05), which was paralleled by an increase in P(Glo) in patients treated with amlodipine (+1.9 +/- 4.3 mm Hg; P <.05) but not in those treated with valsartan. CONCLUSIONS: At similar blood pressure control, valsartan maintained GFR and P(Glo), whereas amlodipine led to glomerular hyperfiltration and an increase in P(Glo). The results might explain the favorable renal outcome with AT(1)-receptor blocker therapy.

Effect of AT1 receptor blockade on endothelial function in essential hypertension.

BACKGROUND: Angiotensin II adversely affects endothelial function and NO availability. We analyzed the effect of AT(1) receptor blockade on endothelium-dependent vasodilation and basal nitric oxide (NO) production and release in hypertensive patients. METHODS AND RESULTS: Sixty patients (53 +/- 10 years) with essential hypertension were randomized to 6 weeks of double-blind therapy with either valsartan (80 mg), hydrochlorothiazide (HCTZ) (25 mg), or placebo once daily. Basal NO production and release was assessed by measuring forearm blood flow (FBF) in response to intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA), and endothelium-dependent vasodilation by measuring FBF in response to intra-arterial administration of acetylcholine, respectively. Intra-arterial infusion of noradrenaline and sodium nitroprusside was used to assess endothelium-independent changes in FBF. Blood pressure (BP) similarly decreased with active treatments (P < .001). After valsartan treatment, the decrease of FBF in response to L-NMMA was augmented (4 micromol/min L-NMMA, -1.3 +/- 1.2 after v -0.5 +/- 1.1 mL/min/100 mL before therapy, P < .02; 8 micromol/min L-NMMA: -1.7 +/- 1.3 after v -1.1 +/- 1.2 mL/min 100 mL before therapy, P < .05). No improvement was found after placebo or HCTZ treatment. Changes in L-NMMA-induced decrease of FBF with valsartan treatment were not related to BP changes. Neither drug substantially modified the response of FBF induced by intra-arterial infusion of acetylcholine, noradrenaline, and sodium nitroprusside. CONCLUSIONS: The AT(1) receptor blockade with valsartan improved basal NO production and release. The effect seems to be BP independent, as BP reduction with HCTZ failed to increase NO availability.

Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects.

OBJECTIVE: The role of the renin-angiotensin system in the regulation of sympathetic nervous activity in human hypertension was evaluated in patients with moderate primary hypertension. For that purpose, the effects of selective angiotensin II (ANG II) receptor blockade by valsartan on sympathetic outflow to the muscle vascular bed and hemodynamic parameters were examined. Results were compared with the effects of the peripherally acting calcium antagonist amlodipine. DESIGN: Eighteen hypertensive but otherwise healthy subjects were examined in a double-blind, placebo-controlled, cross-over protocol receiving either valsartan or amlodipine or placebo for 7 days in a randomized sequence. Treatment periods were separated by washout periods of 2 weeks. METHODS: At the seventh day of treatment, blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), norepinephrine, renin and angiotensin were measured during resting conditions. Additionally, parameters were measured after administration of negative pressure of -15 mmHg to the lower part of the body and after a cold pressor test. RESULTS: Both antihypertensive drugs significantly decreased oscillometrically measured systolic blood pressure and diastolic blood pressure without any difference in effect. While valsartan did not affect the heart rate at rest, amlodipine increased it significantly. Likewise, MSNA was significantly enhanced by amlodipine but not by valsartan. Only ANG II receptor blockade increased renin and angiotensin levels. CONCLUSIONS: Selective ANG II receptor blockade not only decreases blood pressure, but also shifts the baroreflex set-point for the initiation of counter-regulatory reflex responses of heart rate and blood pressure towards normal blood pressure levels. Thus, data suggest that ANG II plays a pathogenetic role in the elevation of the baroreflex set point in primary hypertensive subjects.

Single-channel pharmacology of mibefradil in human native T-type and recombinant Ca(v)3.2 calcium channels.

To study the molecular pharmacology of low-voltage-activated calcium channels in biophysical detail, human medullary thyroid carcinoma (hMTC) cells were investigated using the single-channel technique. These cells had been reported to express T-type whole-cell currents and a Ca(v)3.2 (or alpha 1H) channel subunit. We observed two types of single-channel activity that were easily distinguished based on single-channel conductance, voltage dependence of activation, time course of inactivation, rapid gating kinetics, and the response to the calcium agonist (S)-Bay K 8644. Type II channels had biophysical properties (activation, inactivation, conductance) typical for high-voltage-activated calcium channels. They were markedly stimulated by 1 microM (S)-Bay K 8644, allowing to identify them as L-type channels. The channel termed type I is a low-voltage-activated, small-conductance (7.2 pS) channel that inactivates rapidly and is not modulated by (S)-Bay K 8644. Type I channels are therefore classified as T-type channels. They were strongly inhibited by 10 microM mibefradil. Mibefradil block was caused by changes in two gating parameters: a pronounced reduction in fraction of active sweeps and a slight shortening of the open-state duration. Single recombinant low-voltage-activated T-type calcium channels were studied in comparison, using human embryonic kidney 293 cells overexpressing the pore-forming Ca(v)3.2 subunit. Along all criteria examined (mechanisms of block, extent of block), recombinant Ca(v)3.2 interact with mibefradil in the same way as their native counterparts expressed in hMTC cells. In conclusion, the pharmacologic phenotype of these native human T-type channels--as probed by mibefradil--is similar to recombinant human Ca(v)3.2.