Safety and efficacy of anti-tachycardia pacing in patients with hypertrophic cardiomyopathy implanted with an ICD.

BACKGROUND: In hypertrophic cardiomyopathy (HCM) patients implanted with an implantable cardioverter defibrillator (ICD), clinical outcomes of antitachycardia pacing (ATP) have been poorly explored. In a retrospective analysis of a cohort of consecutive HCM patients implanted with an ICD, we aimed to assess the efficacy, safety, and clinical value of ATP. METHODS: The cohort of HCM patients implanted with a transvenous ICD and followed in our center was assessed for device intervention from implantation to last clinical follow-up. RESULTS: Overall 77 patients (45 males; mean age: 46 ± 16 years) were analyzed. After 67 ± 41 months, 24 patients had 49 ventricular tachycardia/fibrillation (VT/VF) appropriately treated (5.8% per year). Among 39 monomorphic VTs, ATP was effective in 27 (success rate: 69%). Mean time from VT onset to ATP delivery was 9.1 ± 4.9 s. The only clinical variable improving ATP success was use of beta-blockers (81% vs 50%; P = .04). Out of 12 ineffectively treated VTs, one was immediately shocked, four self-terminated after 18 ± 12 s, and seven (18%) were accelerated to a new VT. ATP was also delivered for 27 of 42 inappropriately detected episodes and induced two de novo VTs (7%). In the per patient analysis, 14 out 77 (18%) patients had one or more appropriate and effective ATP (3.4% per year), and only six (8%; 1.4% per year) received more than one ATP. CONCLUSION: ATP is moderately effective for the treatment of monomorphic VTs in HCM patients. However, the rate of appropriate ATP therapies is low, ATP is often prematurely delivered, and ATP-induced arrhythmia degeneration is of concern.

Prognostic Implications of Defibrillation Threshold Testing in Patients With Hypertrophic Cardiomyopathy.

INTRODUCTION: In hypertrophic cardiomyopathy (HCM) patients the need for defibrillation threshold (DFT) testing at the time of ICD implantation is debated. Moreover, its prognostic implications have never been explored. In a cohort of HCM patients we sought to (a) investigate factors prompting DFT testing, (b) evaluate ICD efficacy by testing DFT, (c) compare DFT in patients with and without massive LVH, and (d) assess whether DFT testing predicts shock efficacy for spontaneous VT/VF. METHODS AND RESULTS: We retrospectively analyzed a cohort of HCM patients implanted with an ICD. DFT was tested at the discretion of the implanting physician with a 10 J safety margin. During follow-up, ICD interventions were evaluated. The study population included 66 patients. DFT was determined in 25 (38%) patients. Age (HR: 0.95; 95%CI: 0.92-0.98; P = 0.004) and massive LVH (HR: 6.0; 95%CI: 2.03-18.8; P = 0.001) affected the decision to test DFT. DFT was at least 10 J less than maximal ICD output in 25/25. Safety margin was similar among patients with and without massive LVH (15 ± 3 J vs. 14 ± 2 J; P = 0.42). During follow-up (median 53 months) 15 shocks were delivered for 12 VT/VF in 7 patients. One VF ended spontaneously after a failed shock. Of 4 unsuccessful shocks, 2 occurred in 1 patient with DFT testing and 2 were delivered in 2 patients without. All unsuccessful shocks were ≤35 J. CONCLUSION: Young age and massive LVH prompt DFT testing. Contemporary ICDs are safe and effective in HCM patients independently from the magnitude of LVH. DFT testing does not predict shock efficacy for spontaneous VT/VF.

Eligibility for the Subcutaneous Implantable Cardioverter-Defibrillator in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: High-risk hypertrophic cardiomyopathy (HCM) patients benefit from the implantable cardioverter defibrillator (ICD). The subcutaneous ICD (S-ICD) may provide comparable protection while avoiding the shortcomings of transvenous (TV) leads. We assessed S-ICD eligibility according to surface ECG screening test in a cohort of high-risk HCM patients. METHODS AND RESULTS: 47 HCM patients (3 S-ICD candidates; 41 TV-ICD patients without pacing indication; and 3 pacemaker-dependent TV-ICD patients) underwent 4 screening protocols: standard (n = 44); exercise (n = 33); continuous pacing (n = 44); alternating paced/spontaneous QRS (n = 41). Of the 44 patients in the standard screening group, 41 (93%) were eligible. Max LV thickness was inversely related to the number of qualifying leads (3 leads: 21 ± 4 mm; 2 leads: 22 ± 6 mm; 1 lead: 25 ± 6 mm; no leads: 28 ± 11 mm; P = 0.07). Of the 33 patients in the exercise group, 5 were ineligible (3 after exercise). Of these, 2 became eligible after moving sternal electrodes from the left to the right parasternal line (eligibility rate: 30/33; 91%). Of the 44 patients in the continuous pacing group, 28 (64%) were eligible, 8 of which with right parasternal electrodes. In the paced/spontaneous QRS group (n = 41), 21 patients (51%) had at least 1 eligible lead during pacing and retained compatibility on the same lead during spontaneous rhythm, 5 of which with right parasternal electrodes. CONCLUSIONS: S-ICD screening failure is low in HCM, provided that patients with severe hypertrophy are carefully evaluated. Exercise test should be performed and right parasternal leads tested. Pacemaker patients display lower eligibility rate.

RyR2 Common Gene Variant G1886S and the Risk of Ventricular Arrhythmias in ICD Patients with Heart Failure.

BACKGROUND: Cardiac ryanodine receptor 2 (RyR2) is critical to the electrical homeostasis of cardiomyocytes. Its gene variant rs3766871 entails channel destabilization and enhanced intracellular Ca(2+) oscillation, thus promoting cardiac arrhythmias. We investigated whether the RyR2 rs3766871 variant is associated with aborted sudden cardiac death or ICD therapy for ventricular tachycardia (VT)/fibrillation (VF) in heart failure (HF) patients implanted with a cardioverter defibrillator (ICD). METHODS AND RESULTS: A total of 183 HF patients with primary or secondary prevention ICD were divided in 2 groups. A VT/VF group was composed of secondary prevention patients and primary prevention patients with appropriate ICD intervention for VT/VF. An ICD control group was composed of primary prevention patients free from any appropriate ICD intervention after 43 ± 25 months follow-up. Study subjects were genotyped with respect to the rs3766871 RyR2 gene variant. Hazard ratios (HRs) were derived from Cox proportional-hazards regression analysis. In all, 56 patients constituted the VT/VF group and 127 patients the ICD control group. Male sex (HR: 3.02; 95% CI: 0.99-9.18; P = 0.05), atrial fibrillation (AF; HR: 2.33; 95% CI: 0.89-6.10; P = 0.08), and underuse of ß-blockers (HR: 2.08; 95% CI: 0.84-5.15; P = 0.11) were associated with the VT/VF phenotype. Prevalence of the rs3766871 minor allele was 2.8% in ICD control patients and 8.0% in the VT/VF group (P = 0.02). After adjustment for age, sex, AF, and use of ß-blockers, the rs3766871 minor allele was associated with increased risk of VT/VF (HR: 3.49; 95% CI: 1.14-10.62; P = 0.02). CONCLUSIONS: Our study identifies a significant role of RyR2 rs3766871 minor allele for increased susceptibility to VT/VF in a population of ICD patients with HF.

P-wave duration in lead aVR and the risk of atrial fibrillation in hypertension.

BACKGROUND: Hypertension entails atrial remodeling that affect P-wave (PW) duration on electrocardiogram (ECG). PW indices (e.g., variance, dispersion, and terminal force) are associated with a higher risk for atrial fibrillation (AF), but their calculation requires multiple measurements of PW duration, limiting their use in clinical practice. We evaluated whether PW duration in specific ECG leads may identify patients with increased susceptibility to AF in a population of hypertensive patients. METHODS: In a case-control study, AF and control subjects were matched for age, sex, and left atrial (LA) dimensions. PW duration was measured from digitally stored ECGs. Logistic regression was used to assess the association of PW duration and indices with AF. RESULTS: We enrolled 44 hypertensive AF patients (16 paroxysmal and 28 persistent) and 44 hypertensive controls. AF and control subjects were matched for sex (males, n = 27), age (67 ± 8 years), LA diameter (40 ± 5 mm), and were comparable for left ventricular mass (45 ± 11 g/m(2.7) vs 48 ± 12 g/m(2.7) , P = 0.19), ejection fraction (58 ± 7% in both groups), and prevalence of mild valvular heart disease (7% vs 5%; P = 0.64). PW duration in lead aVR was significantly higher in AF patients as compared with controls (115 ± 18 ms vs 101 ± 14 ms; P < 0.0001) and was the best independent predictor of AF in multivariable logistic regression (PW ≥ 100 ms: RR = 3.7; 95% CI: 1.3-10.3; P = 0.02). CONCLUSIONS: Simple measurement of PW duration in lead aVR allows effective identification of AF patients in a population of hypertensives. Confirmation of this finding in a larger population would provide a simple and effective risk marker of AF in hypertensive patients.

Clinical impact of nonsustained ventricular tachycardia recorded by the implantable cardioverter-defibrillator in patients with hypertrophic cardiomyopathy.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) is a risk factor for sudden death (SD) in hypertrophic cardiomyopathy (HCM). Implantable cardioverter-defibrillators (ICDs) enable accurate assessment of NSVT burden and characteristics. In a cohort of HCM patients with ICD, we characterized Holter- and ICD-retrieved NSVT and evaluated their relationship with prognosis. METHODS AND RESULTS: We studied a cohort of consecutive HCM patients who underwent Holter ECG before receiving a primary prevention ICD. Patients were followed from ICD implantation to the first appropriate ICD therapy. We evaluated the association of NSVT characteristics with ICD interventions. Study cohort included 51 HCM patients (28 males, mean age: 48 ± 15 years). Thirty-four patients (66%) had NSVT at pre-ICD Holter ECG. Out of 17 patients with negative baseline Holter, 7 (41%) showed ICD-NSVT. In patients with both Holter- and ICD-NSVT, these latter were faster (199 ± 27 bpm vs. 146 ± 24 bpm; P < 0.001) and longer (16 ± 8 beats vs. 10 ± 11 beats; P = 0.008) than Holter-NSVT. During follow-up (38 ± 24 months), 11 patients (22%) experienced appropriate ICD therapy. NSVT length in beats (hazard ratio [HR]: 1.05; 95% CI: 1.00-1.10; P = 0.02) but not heart rate (HR: 1.00; 95% CI: 0.98-1.02; P = 0.86) predicted ICD intervention. A simple index of NSVT severity (heart rate × length in beats/100 >28) predicted ICD intervention (HR: 5.45; 95% CI: 1.10-27.32; P = 0.03). CONCLUSIONS: Long-lasting and rapid NSVT recorded during continuous rhythm monitoring predict appropriate ICD intervention in high-risk HCM patients. Further studies should assess whether prolonged rhythm monitoring may assist in evaluating patients at intermediate risk of SD, in which the decision to implant an ICD needs to be individualized.

Osteopontin and galectin-3 predict the risk of ventricular tachycardia and fibrillation in heart failure patients with implantable defibrillators.

BACKGROUND: Myocardial extracellular matrix remodelling provides electrical heterogeneity entailing ventricular tachycardia/fibrillation (VT/VF) in heart failure (HF) patients. Osteopontin (OPN) and Galectin-3 (Gal-3) are fibrosis markers and may reflect the extension of the arrhythmogenic substrate. We assessed whether plasma OPN and Gal-3 predict the risk of sustained VT/VF in a cohort of HF patients with implantable cardioverter-defibrillator (ICD). METHODS: A total of 75 HF patients underwent pre-ICD implantation clinical evaluation and assessment of plasma OPN and Gal-3. The primary endpoint was the time to the occurrence of the first sustained VT/VF. Hazard ratios (HR) were derived from Cox proportional-hazards analysis. RESULTS: Patients with coronary artery disease (CAD) had higher plasma OPN (79.8 ± 44.0 ng/mL vs. 66.0 ± 31.8 ng/mL; P = 0.04). Both Gal-3 (r = -0.38; P = 0.01) and OPN (r = -0.27; p = 0.01) were negatively related to estimated glomerular filtration rate. After 29 ± 17 months, 20 patients (27%) reached the primary endpoint. Patients with VT/VF had higher plasma OPN and Gal-3 (97.4 ± 51.7 ng/mL vs. 65.9 ± 31.3 ng/mL; P = 0.002 and 19.7 ± 8.5 ng/mL vs. 16.2 ± 6.2 ng/mL; P = 0.05). In univariate analysis, OPN (log-OPN, HR: 32.4; 95%CI: 3.9-264.7; P = 0.001) and Gal-3 (HR: 1.05; 95%CI: 1.00-1.11; P = 0.04) predicted sustained VT/VF. In multivariable analysis, both OPN (HR: 41.4; 95%CI: 3.8-441.9; P = 0.002) and Gal-3 (HR: 1.06; 95%CI: 1.00-1.12; P = 0.03) retained their prognostic power after correction for age, sex, history of MI, EF, NYHA class, eGFR, use of ACE-I, and amiodarone. CONCLUSIONS: Plasma OPN and Gal-3 predict sustained VT/VF in HF patients at high risk for SCD. Larger prospective studies should outline the role of these biomarkers in predicting SCD on top of conventional risk stratification.

Autonomic cardiovascular control and cardiac arrhythmia in two pregnant women with hypertrophic cardiomyopathy: Insights from ICD monitoring.

In women with hypertrophic cardiomyopathy (HCM), pregnancy prompts major changes in hemodynamic and cardiac autonomic function that may precipitate heart failure (HF) or increase the risk of cardiac arrhythmia. We report the clinical follow-up of two patients with non-obstructive HCM implanted with a cardioverter defibrillator (ICD) allowing for continuous analysis of heart rate (HR), heart rate variability (HRV) and cardiac arrhythmia throughout the entire course of pregnancy. Both patients experienced increased HR and decreased HRV from the early stages of pregnancy, which persisted until delivery. Premature ventricular contractions (PVCs) and runs of non-sustained ventricular tachycardia (NSVT) reached a peak in the second and third trimesters, concurrent with sympathetic hyperactivity. In one patient with baseline NYHA class II HF symptoms, increased PVCs and NSVT were consistent with the deterioration of HF, supporting the decision to bring the delivery forward. While both patients experienced a persistent increase in sympathetic tone and ventricular ectopic activity, no life-threatening arrhythmias were documented. During pregnancy, patients with hypertrophic cardiomyopathy develop progressive neuroautonomic imbalance, prompting an increase in non-sustained ventricular arrhythmia. This enhanced arrhythmia burden warrants close follow-up and rhythm assessment during the third trimester, especially in women who have heart failure symptoms before pregnancy. Implantable cardioverter defibrillators provide a continuous analysis of heart rate variability and arrhythmia burden that supports therapeutic decision-making during follow-up.

Clinical and electrocardiographic features of complete heart block after blunt cardiac injury: A systematic review of the literature.

The underlying mechanisms and temporal course of complete heart block (CHB) after blunt cardiac injuries (BCIs) are poorly understood, and a systematic analysis of available data is lacking. In this systematic review, PubMed was searched for publications of reported cases of CHB-BCI analyzing clinical findings, electrocardiographic features, temporal course, and outcomes. Case reports on CHB-BCI were available for 50 patients, mainly secondary to traffic or sport accidents. A fatal outcome occurred in 10 of 50 (20%) of patients, while a structural damage of the atrioventricular (AV) conductive system was evident in 4 of 8 (50%) of necropsy studies. Clinical manifestation of CHB-BCI occurred within 72 hours of injury in 38 of 47 (∼80%) of patients, and 1:1 AV conduction was restored within 7-10 days in about half of early survivors. Permanent pacemaker implantation was indicated in 22 of 42 (∼50%) of early survivors because of recurrent or permanent CHB. Cardiac troponins, when analyzed, were elevated in 12 of 13 (∼90%) of patients, and electrocardiographic features of aberrancy were present in 29 of 40 (>70%) of patients. In conclusion, CHB secondary to BCI is associated with 20% mortality mainly occurring in the early posttraumatic period and most of the deaths are due to or triggered by this malignant arrhythmia. Recurrent or permanent CHB requiring pacemaker implantation occurs in ∼50% of survivors. A structural damage of the AV conductive system can be found in 50% of necropsy studies.

Restrictive cardiomyopathy and pseudoxanthoma elasticum skin lesions.

: We report a rare case of a patient with AL amyloidosis and pseudoxanthoma elasticum skin lesions. An association between these two diseases has been previously described as amyloid elastosis in only six cases, but cardiac findings were not fully elucidated. The peculiarity of our case is that a severe cardiac involvement influenced the prognosis negatively. Furthermore, the electron microscopic examination did not show all the peculiar histopathological findings of amyloid elastosis, precluding a final diagnosis of this disease.

Angiotensin receptor antagonists to prevent sudden death in heart failure: does the dose matter?

International guidelines recommend ICD implantation in patients with severe left ventricular dysfunction of any origin only after careful optimization of medical therapy. Indeed, major randomized clinical trials suggest that suboptimal use of fundamental drugs, such as ACE inhibitors (ACE-i) and beta-blockers, may affect ICD shock-free survival, sudden cardiac death (SCD), and overall mortality. While solid evidence in favour of pharmacological therapy based on ACE-i with or without beta-blockers is available, data on SCD in HF patients treated with angiotensin receptor blockers (ARBs) are limited. The present paper systematically analyses the impact of ARBs on SCD in HF and reviews the contributory role of the renin-angiotensin system (RAS) to the establishment of arrhythmic substrates. The following hypothesis is supported: (1) the RAS is a critical component of the electrical remodelling of the failing myocardium, (2) RAS blockade reduces the risk of SCD, and (3) ARBs represent a powerful tool to improve overall survival and possibly reduce the risk of SCD provided that high doses are employed to achieve optimal AT1-receptor blockade.