Reappraisal on pharmacological and mechanical treatments of heart failure.

Heart failure (HF) is a highly frequent disorder with considerable morbidity, hospitalization, and mortality; thus, it invariably places pressure on clinical and public health systems in the modern world. There have been notable advances in the definition, diagnosis, and treatment of HF, and newly developed agents and devices have been widely adopted in clinical practice. Here, this review first summarizes the current emerging therapeutic agents, including pharmacotherapy, device-based therapy, and the treatment of some common comorbidities, to improve the prognosis of HF patients. Then, we discuss and point out the commonalities and areas for improvement in current clinical studies of HF. Finally, we highlight the gaps in HF research. We are looking forward to a bright future with reduced morbidity and mortality from HF.

Cardiac resynchronization therapy-induced acute shortening of QRS duration predicts long-term mortality only in patients with left bundle branch block.

AIMS: QRS narrowing with initiation of biventricular pacing might be an acute electrocardiographic indicator of correction of left bundle branch block (LBBB)-induced depolarization delay and asynchrony. However, its impact on prognosis remains controversial, especially in non-LBBB patients. Our goal was to evaluate the impact of QRS narrowing on long-term mortality and morbidity in a large cohort of patients undergoing cardiac resynchronization therapy (CRT) with different pre-implantation QRS types: LBBB, non-LBBB, and permanent right ventricular pacing. METHODS AND RESULTS: This study included consecutive patients who underwent CRT device implantation. Study endpoints: death from any cause or urgent heart transplantation and death from any cause/urgent heart transplantation or hospital admission for heart failure. All pre- and post-implantation electrocardiograms were analysed using digital callipers, high-amplitude augmentation, 100 mm/s paper speed, and global QRS duration measurement method. A total of 552 CRT patients entered the survival analysis. During the 9 years observation period, 232 (42.0%) and 292 (52.9%) patients met primary and secondary endpoints, respectively. QRS narrowing predicted survival in the Kaplan-Meier analysis only in patients with LBBB. Multivariate Cox regression model showed that QRS narrowing was the major determinant of both study endpoints, with hazard ratios of 0.46 and 0.43, respectively. There was a strong relationship between mortality risk and shortening/widening of the QRS, albeit only in the LBBB group. Patients with non-LBBB morphologies had unfavourable prognosis similar to that in LBBB patients without QRS narrowing. CONCLUSION: Acute QRS narrowing in patients with LBBB might be a desirable endpoint of CRT device implantation.

Ventricular electrical delay as a predictor of arrhythmias in patients with cardiac resynchronization implantable cardioverter defibrillator.

BACKGROUND: Left ventricular (LV) remodeling and clinical response to cardiac resynchronization therapy (CRT) is inversely related to electrical dyssynchrony, measured as LV lead electrical delay (QLV). Presence of atrial or ventricular arrhythmia is correlated with worsening heart failure and LV remodeling. OBJECTIVE: We sought to assess the association of QLV with arrhythmic events in CRT recipients. METHODS: We identified patients implanted with a CRT device at our center. QLV interval was measured and corrected for baseline QRS (cQLV). We performed multivariable Logistic regression to assess the effect of cQLV on the occurrence of atrial/ventricular arrhythmic events. RESULTS: Sixty-nine patients were included in analyses. The cQLV was significantly shorter in patients with atria tachycardia/supraventricular tachycardia (AT/SVT) events compared to patients without AT/SVT events (43.4 ± 22% vs. 60.3 ± 26.7%, p = .006). In contrast, no significant difference in cQLV was observed between patients with and without ventricular tachycardia/fibrillation (VT/VF) events (46.2 ± 25.4% vs. 56 ± 25.7%, p = .13). cQLV was significantly shorter in patients with new onset AT/SVT events compared to those without (38.3 ± 22.2% vs. 55.7 ± 25.7%, p = .028). In contrast, no significant difference in cQLV was observed between patients with and without new onset VT/VF events (44.2 ± 25.2% vs. 56.3 ± 25.5%, p = .069). Following adjusted analyses, cQLV was a significant predictor of AT/SVT, but not for VT/VF. CONCLUSION: cQLV is a simple measure that can identify a vulnerable cohort of CRT patients at increased risk for atrial tachyarrhythmias, and hence can predict reverse remodeling and clinical response to CRT treatment.

Multisite cardiac resynchronization therapy for traditional and non-traditional indications.

PURPOSE: Multisite cardiac resynchronization therapy (MSCRT) with dual-vein left ventricular (LV) pacing has theoretical advantages over conventional CRT in faster and more physiological LV activation. We aimed to define indications, feasibility, safety, acute, and long-term results of MSCRT. METHODS: All patients implanted with MSCRT during 2008-2014 in a single center were reviewed and analyzed. RESULTS: Thirty-nine patients (90% CRT-defibrillators, 64 ± 9 years, 85% male, 74% ischemic etiology) were included. Four groups of indications were recognized: (1) significant tricuspid regurgitation (TR) in patients planned for device implantation without right ventricular lead (n = 3). Follow-up (f/u) of 4 ± 3 years showed major symptomatic improvement in all, with stable LV size and function and deferral of valve surgery; (2) severe heart failure with reduced ejection fraction (HFrEF) and refractory ventricular tachycardia (VT) (n = 4). Except for 1 early death for acute renal failure, all others showed no VT episodes and HF improvement (f/u 4.5 ± 0.5 years); (3) severe HFrEF and wide QRS (≥ 150 ms) or failure of biventricular pacing to narrow QRS during implantation (n = 5). One patient had periprocedural mortality. The others had major clinical improvement; (4) severe HF and narrow QRS/RBBB (n = 27). 23/24 patients with available f/u of 3 ± 1.7 years improved clinically and 57% had EF improvement. In 3 patients, LV1 was disabled and one had LV2 dislodgement. CONCLUSIONS: MSCRT is feasible, safe, and valuable in selected patients with a need to avoid RV lead during device implantation, refractory VT with no other solution, severe HFrEF with wide QRS or CRT non-responsiveness, and severe HF without LBBB. Randomized controlled studies are required.

Cardiovascular drug utilization post-implant is related to clinical outcome in heart failure patients receiving cardiac resynchronization therapy.

BACKGROUND: In select patients with heart failure, cardiac resynchronization therapy (CRT) is the most common complementary treatment besides medical treatment. We aimed to assess the association between post CRT-implant changes in cardiovascular medication and cardiovascular mortality and heart failure hospitalization. METHODS: 211 patients on optimal medical therapy eligible for CRT were retrospectively included in this study (72 ± 7 years, 80% male, 66% left bundle branch block, 48% dilated cardiomyopathy and investigated at baseline and after 6 months. Follow-up with medication, biochemical markers and echocardiography was performed and 3-year mortality data was collected. RESULTS: At 6 months post-implant the cohort was divided into two groups; 157 patients had low dosage furosemide treatment (up to 40 mg) and 54 patients were treated with high dosage (> 40 mg). A composite endpoint of heart failure hospitalization and all-cause mortality was evaluated at 30 months (881 ± 267 days) after the 6-month visit. In multivariate Cox regression analysis, pa-tients in the high dose diuretics group had a higher risk of the primary endpoint (HR 1.9 [1.1-3.4], p = 0.033), but treatment with high dose diuretics was not associated with improved clinical symptoms (r = 0.031, p = 0.64). CONCLUSIONS: High dosage of loop-diuretics was associated with worse medium-term clinical outcome in CRT treated patients. It is unclear whether there is a direct causality between these associations, or if higher prescribed dosage of loop-diuretics is just a marker of more severe disease. Higher dose loop diuretics do not necessarily improve the symptoms and may be harmful to the patient. Prospective trials are warranted to further elucidate these findings. (Cardiol J 2017; 24, 4: 374-384).

Advances in Heart Failure Management: Improving Outcomes With Innovation.

Heart failure (HF) is a chronic and complex disease entity with an enormous morbidity and mortality. Many of the therapies used in the management of HF were developed decades ago, but recently more novel monitoring and therapeutic strategies have emerged. The employment of these strategies may reduce morbidity and mortality in patients with HF. This article reviews the epidemiology of HF and some of the novel strategies developed to assess risk and monitor these challenging patients. It also discusses the evidence behind some of the newer treatments available that are recently included in the HF management guidelines. Various devices used in the treatment of HF, some of which remain investigational, are also discussed. Novel strategies for remote monitoring and new pharmacologic therapies may be useful in improving morbidity and mortality in patients with HF.

Management of functional Sprint Fidelis leads at cardiac resynchronization therapy-defibrillator generator replacement: a novel option for preventing inappropriate shocks from lead failure in fragile patients with high risk of sudden death.

AIMS: In patients with a functional Sprint Fidelis lead at generator replacement, the manufacturer recommended to either continue to use the existing lead or replace it with a new lead. For those patients who continue to use a functional Fidelis lead, the risk of inappropriate shocks remains present if the lead fails in the future. We evaluated the feasibility of an alternative approach at the time of cardiac resynchronization therapy-defibrillator (CRT-D) generator replacement in patients with a functional bipolar left ventricular (LV) lead for prevention of inappropriate shocks from future Fidelis lead failure. METHODS AND RESULTS: During the procedure, the pace/sense IS-1 connection pin of the functional Fidelis lead was intentionally inserted into the LV port of the new CRT-D generator, while the existing bipolar LV lead IS-1 connection pin was inserted into the right ventricular (RV) pace/sense port. After such switching, the existing bipolar LV lead was used for functional LV pacing/sensing, while the Fidelis lead was used for functional RV pacing and high voltage shock only and could no longer be used for the purpose of sensing and detecting. This approach precluded oversensing and inappropriate shocks should the functional Fidelis lead fail in the future. Six fragile patients, who were not considered suitable candidates for lead replacement, underwent the alternative approach. During a follow-up of 35 ± 23 months, the CRT-D system functioned normally in five patients. The Fidelis lead fractured in one patient 7 months after generator replacement. The malfunction was detected promptly and the defected lead was replaced. No inappropriate detections or shock was triggered. CONCLUSIONS: In CRT-D patients with a functional Fidelis lead and a bipolar LV lead, switching of the Fidelis lead pace/sense IS-1 pin with the bipolar LV lead IS-1 pin at generator replacement did not affect normal system function. This novel approach may be valuable in fragile patients with high risk of sudden death for prevention of inappropriate shocks triggered by oversensing from a malfunctioning Fidelis lead.

Sex Differences in Inappropriate ICD Device Therapies: MADIT-II and MADIT-CRT.

INTRODUCTION: Approximately 10-20% of ICD recipients receive inappropriate device therapies. The purpose of this study was to compare the frequency of inappropriate therapies (IT) between men and women enrolled in MADIT II and MADIT-CRT, and assess for potential adverse outcomes. METHODS: The electrograms for each ICD or CRT-D therapy, defined as either ATP or shock, were reviewed by adjudication committees for both studies. ICD therapy was considered inappropriate if it was delivered for reasons other than VT/VF. The rhythm triggering IT was categorized as atrial fibrillation/flutter, SVT, or inappropriate sensing when possible. RESULTS: One thousand nine hundred and fifty-four men and 556 women received ICD or CRT-D devices. The risk of IT was significantly lower in women than men (9.2% vs. 13.5%, P = 0.006). The most common cause of IT in men was atrial fibrillation (38%) and SVT in women (43%). Inappropriate shock was not associated with increased mortality in either women (HR 0.82 [95% CI 0.11-6.08]; P = NS) or men (HR 1.37 [95% CI 0.75-2.48]; P = NS) by multivariate analysis. Conversely, appropriate shock therapy strongly correlated with increased risk of death during subsequent post-shock follow-up in women (HR 5.99 [95% CI 2.75-13.02]; P < 0.0001) and men (HR 2.61 [95% CI 1.82-3.74]; P < 0.0001). CONCLUSIONS: Women experience significantly less IT than men, partially explained by the increased frequency of atrial fibrillation in men. IT was not associated with increased mortality in either sex. Appropriate shock therapy was a strong predictor of death in both, with women showing a 2-fold higher risk than men during post-shock long-term follow-up.

Clinical impact, safety, and efficacy of single- versus dual-coil ICD leads in MADIT-CRT.

BACKGROUND: Current data on efficacy, safety and impact on clinical outcome of single- versus dual-coil implantable cardioverter-defibrillator (ICD) leads are limited and contradictory. METHODS: Defibrillation threshold (DFT) at implantation and first shock efficacy were compared in patients implanted with single- versus dual-coil ICD leads in MADIT-CRT. The risk for atrial tachyarrhythmias and all-cause mortality were evaluated. Short- (< 30 days after the implantation) and long-term (throughout the entire study duration) complications were assessed. RESULTS: Patients with dual-coil ICD leads had significantly lower DFTs compared to patients with single-coil ICD leads (17.6 ± 5.8 J vs 19.4 ± 6.1 J, P < 0.001). First shock efficacy was similar among patients with dual and single-coil ICD leads (89.6% vs 92.3%, P = 1.00). When comparing patients with dual versus single-coil ICD leads, there was no difference in the risk of atrial tachyarrhythmias (HR = 1.57, 95% CI: 0.81-3.02, P = 0.18), or in the risk of all-cause mortality (HR = 1.10, 95% CI: 0.58-2.07, P = 0.77). Patients implanted with single- or dual-coil ICD lead had similar short and long-term complication rates (short-term HR = 0.96, 95% CI: 0.56-1.65, P = 0.88, long-term procedure-related HR = 0.99, 95% CI: 0.62-1.59, P = 1.00, long-term ICD lead related: HR = 1.2, 95% CI: 0.5-2.9, P = 0.68) during the mean follow-up of 3.3 years. CONCLUSIONS: Patients with single-coil ICD leads have slightly higher DFTs compared to those with dual-coil leads, but the efficacy, safety, and clinical impact on atrial tachyarrhythmias, and mortality is similar. Implantation of single-coil ICD leads may be favorable in most patients.

Postoperative performance of the Quartet® left ventricular heart lead.

INTRODUCTION: The Quartet(®) left ventricular (LV) lead is the first with 4 pacing electrodes (tip and 3 rings) that enables pacing from 10 different pacing vectors. Postoperative performance of this lead was evaluated in a prospective, nonrandomized, multicenter IDE study. METHODS: Patients with standard indications for CRT-D were enrolled. Electrical performance and presence of phrenic nerve stimulation (PNS) were assessed during pacing from each of 10 vectors at predischarge (within 7 days), 1 month, and 3 months postimplant. RESULTS: The Quartet LV lead was implanted successfully in 170 patients (95.5% implant success rate, 68 ± 11 years, 68.5% male, LVEF: 25 ± 7%, NYHA class III: 98.3% and class IV: 1.7%). Mean follow-up was 4.7 ± 1.9 months. Capture threshold and impedance for each of the 10 LV lead pacing vectors remained stable during follow-up. LV lead dislodgement occurred in 6 (3.5%) patients and PNS was observed in 23 (13.5%) patients. PNS was resolved noninvasively in all 23 (100%) patients, either by reprogramming to pace from the additional LV lead pacing vectors alone (13 pts, 56.5%), reprogramming to pace from the additional LV lead pacing vectors and reprogramming pacing output (4 pts, 17.4%), or by reprogramming pacing output alone (6 pts, 26.1%). CONCLUSIONS: The Quartet LV lead electrical performance was stable and was associated with a high implant success and low dislodgement rate during 3-month follow-up. In all patients with PNS, the 10 pacing vectors combined with reduced output programming enabled the elimination of PNS noninvasively.